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Yang M, Ji W, Xu N, zong C, Gu J, Guo X, Zhang L. Association of vitamin D receptor polymorphisms with colorectal cancer susceptibility: A systematic meta-analysis. Medicine (Baltimore) 2023; 102:e32575. [PMID: 36607855 PMCID: PMC9829264 DOI: 10.1097/md.0000000000032575] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Recent studies have reported an association between vitamin D receptor (VDR) polymorphisms and colorectal cancer (CRC) risk; however, the results are controversial. This meta-analysis was performed to investigate whether the Cdx-2, Tru9I, FokI, BsmI, TaqI, and ApaI polymorphisms were correlated with CRC susceptibility. METHODS All potential studies were retrieved by searching the PubMed, EMBASE, and Cochrane Library databases through October 2, 2021. Odds ratios (ORs) with 95% confidence intervals were used to evaluate the correlation between VDR gene Cdx-2, Tru9I, FokI, BsmI, TaqI, and ApaI polymorphisms and CRC risk. RESULTS In this meta-analysis, the BsmI variant was significantly correlated with a lower risk of CRC, especially in Caucasian population (B vs b: OR 0.94, 95%CI 0.90-0.99; BB vs bb: OR 0.88; 95%CI 0.79-0.97; BB vs Bb/bb: BB vs Bb/bb: OR 0.89; 95%CI 0.81-0.98). A statistically significant result from the FokI polymorphism was observed in colon cancer rather than rectal cancer (Ff vs FF: OR 0.86, 95%CI 0.84-0.93; ff/Ff vs FF: OR 0.88, 95%CI 0.79-0.98; ff vs Ff/FF: OR 0.90, 95%CI 0.82-0.99). Similarly, Cdx-2 polymorphism was found to be associated with decreased CRC risk among Africans (C vs c: OR 0.50, 95%CI 0.33-0.75; CC vs cc: OR 0.09, 95%CI 0.01-0.77; Cc vs cc: OR 0.49, 95%CI 0.30-0.81; CC/Cc vs cc: OR 0.45, 95%CI 0.28-0.74,). CONCLUSION Our findings indicate that VDR polymorphisms are significantly associated with CRC risk.
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Affiliation(s)
- Maoquan Yang
- Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang, China
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Wansheng Ji
- Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang, China
- Experimental Center for Medical Research, Weifang Medical University, Weifang, China
| | - Ning Xu
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Chuanju zong
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Jinhua Gu
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Xiaojing Guo
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Li Zhang
- Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang, China
- *Correspondence: Li Zhang, Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang, China. e-mail:
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Cui Y, Li H, Zhan H, Han T, Dong Y, Tian C, Guo Y, Yan F, Dai D, Liu P. Identification of Potential Biomarkers for Liver Cancer Through Gene Mutation and Clinical Characteristics. Front Oncol 2021; 11:733478. [PMID: 34604069 PMCID: PMC8484954 DOI: 10.3389/fonc.2021.733478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/19/2021] [Indexed: 11/13/2022] Open
Abstract
Liver cancer is a common malignant tumor worldwide, which is a serious threat to the health of people. We try to investigate some mutations and clinical indicators as candidate markers for the development of liver cancer through targeted region capture technology combined with next-generation sequencing. We collected peripheral blood and liver cancer tissue samples from 32 liver patients concurrently. The SeqCap EZ Prime Choice Probe was used to perform the targeted enrichment; this probe captures 1,000 known cancer-associated genes. We calculated the tumor mutation burden (TMB) for each patient. The high-frequency mutations and these relative genes were identified. Eventually, survival analysis was performed based on the mutations and clinical indicators. In 32 liver patients, a total of 29 high-frequency mutations were investigated. They were located in 25 genes, which were enriched in 9 cellular components (CCs), 6 molecular functions (MFs), and 21 biological processes (BPs). Among them, EZH2 c.1544A>G and CCND1 c.839A>T had the highest mutation frequency (5/32). In the protein-protein interaction (PPI) network, EZH2-DNMT3A, NOTCH1-CCND1, and ABL1-CCND1 were the top three pairs. The survival analysis showed that there were significant differences in progression-free survival (PFS) and overall survival (OS) between the Karnofsky performance score (KPS) groups. The PFS and OS in the TMB high group were higher than those in the TMB low group. OS and tumor stage had a remarkable relationship. In conclusion, EZH2 c.1544A>G and CCND1 c.839A>T might be potential biomarkers of liver cancer. TMB might be used as a prognosis and survival indicator of liver cancer.
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Affiliation(s)
- Yunlong Cui
- Department of Hepatobiliary Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Hua Li
- Department of Endoscopy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Hongjie Zhan
- Department of Gastric Cancer, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Tao Han
- College of Engineering, Peking University, Beijing, China
| | - Yixuan Dong
- Graduate School, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
| | - Caijuan Tian
- Tianjin Marvel Medical Laboratory, Tianjin Marvelbio Technology Co., Ltd., Tianjin, China
| | - Yixian Guo
- Tianjin Marvel Medical Laboratory, Tianjin Marvelbio Technology Co., Ltd., Tianjin, China
| | - Fang Yan
- Tianjin Marvel Medical Laboratory, Tianjin Marvelbio Technology Co., Ltd., Tianjin, China
| | - Dong Dai
- Department of Molecular Imaging and Nuclear Medicine, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Pengfei Liu
- Department of Oncology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
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Ye CC, Wang J. E-cadherin (CDH1) gene -160C/A polymorphism and the risk of colorectal cancer: A meta-analysis involving 17,291 subjects. J Gene Med 2021; 23:e3370. [PMID: 34097324 DOI: 10.1002/jgm.3370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 05/29/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The E-cadherin (CDH1) polymorphism has been implicated in the susceptibility to colorectal cancer (CRC). However, the results remain inconclusive. The present meta-analysis aimed to investigate the association between the CDH1-160C/A polymorphism and CRC risk. METHODS Relevant studies were retrieved by searching PubMed, Web of Science, Google Scholar, the Cochrane Library, Embase, CNKI and Wanfang databases up to 11 March 2021. Pooled odds ratio and 95% confidence interval were calculated using either the fixed- or random-effects model. Quality evaluation was carried out using Newcastle-Ottawa Scale (NOS). A trial sequential analysis (TSA) was conducted to reduce the risk of type I error. RESULTS In total, 16 studies from 14 articles with 8699 patients and 8592 controls were included. In general, all studies were of high quality (NOS score higher than 6). Overall, no significant associations between the CDH1 -160C/A polymorphism and CRC risk were detected. In subgroup analysis by ethnicity, source of control, genotyping method and location, significant associations were found between the CDH1-160C/A polymorphism and the risk of CRC in the Caucasians and the hospital-based subgroup. Furthermore, 10 studies with 8019 subjects reported the association between the polymorphism and clinical characteristics in CRC patients, and we found that the CDH1-160C/A polymorphism might show a protective role in the distal CRC subgroup. By TSA, the findings in the present study were based on sufficient evidence in Caucasians, but not in Asians. CONCLUSIONS This meta-analysis suggests that the CDH1-160C/A polymorphism may be an important protective factor for CRC in Caucasians and a hospital-based subgroup. Moreover, the polymorphism show a protective role in the distal CRC group. However, large and well-designed studies are warranted to validate our findings, especially for Asians.
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Affiliation(s)
- Chun-Cui Ye
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Jun Wang
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
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Abstract
Increasing scientific evidence supports the link between vitamin D and cancer risk. The active metabolite 1,25(OH)2D exerts its activity by binding to the vitamin D receptor (VDR), an intracellular receptor that mediates transcriptional activation and repression of target genes. The binding of 1,25(OH)2D to VDR is able to regulate hundreds of different genes. VDR is active in virtually all tissues including the colon, breast, lung, ovary, bone, kidney, parathyroid gland, pancreatic b-cells, monocytes, T lymphocytes, melanocytes, keratinocytes, and also cancer cells.The relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies.We have carried out a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies considering ethnicity as a key factor for heterogeneity.Up to December 2018, we identified 176 independent studies with data to assess the risk of breast, prostate, colorectal, skin (melanoma and non-melanoma skin cancer), lung, ovarian, kidney, bladder, gallbladder, esophageal, thyroid, head and neck, liver and pancreatic cancer, oral squamous cell carcinoma, non-Hodgkin lymphoma, multiple myeloma and sarcoma.Significant associations with VDR polymorphisms have been reported for prostate (Fok1, Bsm1, Taq1, Apa1, Cdx2), breast (Fok1, Bsm1, Taq1, Apa1, CdX2), colorectal (Fok1, Bsm1, Taq1, Apa1), and skin cancer (Fok1, Bsm1, Taq1). Very few studies reported risk estimates for the other cancer sites.Conflicting data have been reported for most malignancies, and at present, it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer risk. It seems probable that other factors such as ethnicity, phenotype, 25(OH)D plasma levels, and UV radiation exposure play a role as confounding factors and introduce heterogeneity.To conclude, there is some indication that VDR polymorphisms may modulate the risk of some cancer sites and in future studies VDR genetic variation should be integrated also with assessment of vitamin D status and stratified by ethnicity.
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Laskar S, Kundu S, Das R, Choudhury Y, Ghosh SK. Clinically significant variants associated with nasopharyngeal carcinoma: Findings of a meta-analysis study. Meta Gene 2020. [DOI: 10.1016/j.mgene.2020.100688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2022] Open
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Li W, Xiao D, Wu H, Xu L. The epithelial cadherin -160C/A polymorphism is associated with decreased risk of colorectal cancer: a case-control study. Clin Exp Med 2020; 20:73-78. [PMID: 31625007 DOI: 10.1007/s10238-019-00586-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 10/11/2019] [Indexed: 01/03/2023]
Abstract
The epithelial cadherin (CDH1) is an important determinant of tumor progression. Previous studies have indicated that the CDH1 -160C/A polymorphism was associated with the risk of colorectal cancer (CRC). However, they yielded conflicting results. Thus, we conducted this case-control study to evaluate the association between the CDH1 -160C/A polymorphism and susceptibility to CRC in a Chinese population. We recruited 351 cases and 411 controls in this case-control study. The genotype of the CDH1 -160C/A polymorphism was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). This study found that the CDH1 -160C/A polymorphism was associated with decreased risk of CRC in this Chinese Han population. Subgroup analyses showed that the CDH1 -160C/A polymorphism decreased the risk of CRC among the males and non-drinkers. In addition, a significantly decreased risk was observed in CRC patients with tumor size ≤ 5 cm, and AA genotype showed a protective role in the CRC patients with no lymph node metastasis. In conclusion, this study shows that CDH1 -160C/A polymorphism is associated with decreased risk of CRC in a Chinese Han population.
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Affiliation(s)
- Wenhuan Li
- Department of Gastrointestinal Surgery, The Affliated Wenling Hospital of Wenzhou Medical University, The First People's Hospital of Wenling, No. 333 Chuan'an South Road, Chengxi Street, Wenling, Taizhou, China
| | - Deshuang Xiao
- Department of Liver and Gallbladder Surgery, The Affliated Wenling Hospital of Wenzhou Medical University, The First People's Hospital of Wenling, No. 333 Chuan'an South Road, Chengxi Street, Wenling, Taizhou, China
| | - Huawen Wu
- Department of Gastrointestinal Surgery, The Affliated Wenling Hospital of Wenzhou Medical University, The First People's Hospital of Wenling, No. 333 Chuan'an South Road, Chengxi Street, Wenling, Taizhou, China
| | - Lewei Xu
- Department of Surgery, The Affliated Wenling Hospital of Wenzhou Medical University, The First People's Hospital of Wenling, No. 333 Chuan'an South Road, Chengxi Street, Wenling, Taizhou, China.
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Elshazli RM, Toraih EA, Elgaml A, Kandil E, Fawzy MS. Genetic polymorphisms of TP53 (rs1042522) and MDM2 (rs2279744) and colorectal cancer risk: An updated meta-analysis based on 59 case-control studies. Gene 2020; 734:144391. [PMID: 32001373 DOI: 10.1016/j.gene.2020.144391] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 01/16/2020] [Accepted: 01/22/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Several earlier reports implicated TP53 (rs1042522) and MDM2 (rs2279744) variants in outcome of colorectal cancer (CRC), but with inconclusive findings. This current meta-analysis designed to uncover the role of these variants in CRC risk. METHODOLOGY Two independent investigators extracted 59 eligible case-control studies from different electronic databases involving Scopus, Web of Science and PubMed prior to June 2019. Pooled odds ratios (ORs) and "95% confidence intervals (CIs)" were computed for different hereditary models. Stratification and heterogeneity analyses, and "Begg's funnel plots" were conducted. In silico data analyses of the functional and structural properties of the study variants were applied. RESULTS In general, 47 and 16 case-control reports for TP53 (11,589 patients and 13,622 controls) and MDM2 (6841 CRC patients and 8792 healthy controls), respectively were enrolled in this meta-analysis. A significant association of TP53 (rs1042522) variant with increased CRC risk in overall pooled subjects under recessive model [(CC vs. GC + GG, OR = 1.134, 95% CI = 1.006-1.278, P = 0.039)] was observed. Moreover, an evidence of MDM2 (rs2279744) association with increased CRC risk in overall pooled subjects under dominant and heterozygote models [(TG + GG vs. TT, OR = 1.120, 95% CI = 1.003-1.250, P = 0.044) and (TG vs. TT, OR = 1.189, 95% CI = 1.076-1.313, P = 0.001), respectively] was reported. Additionally, TP53 (rs1042522) and MDM2 (rs2279744) showed an association with CRC risk among Asians and Africans under a recessive model, and among Asians under different genetic models, respectively, by stratification analysis. CONCLUSION TP53 (rs1042522) and MDM2 (rs2279744) variants might represent candidate risk factors for CRC susceptibility.
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Affiliation(s)
- Rami M Elshazli
- Department of Biochemistry and Molecular Genetics, Faculty of Physical Therapy, Horus University - Egypt, New Damietta, Egypt.
| | - Eman A Toraih
- Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; Genetics unit, Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Egypt
| | - Abdelaziz Elgaml
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Department of Microbiology and Immunology, Faculty of Pharmacy, Horus University - Egypt, New Damietta, Egypt
| | - Emad Kandil
- Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA
| | - Manal S Fawzy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia
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Matsuoka T, Yashiro M. Precision medicine for gastrointestinal cancer: Recent progress and future perspective. World J Gastrointest Oncol 2020; 12:1-20. [PMID: 31966910 PMCID: PMC6960076 DOI: 10.4251/wjgo.v12.i1.1] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 10/12/2019] [Accepted: 11/04/2019] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal (GI) cancer has a high tumor incidence and mortality rate worldwide. Despite significant improvements in radiotherapy, chemotherapy, and targeted therapy for GI cancer over the last decade, GI cancer is characterized by high recurrence rates and a dismal prognosis. There is an urgent need for new diagnostic and therapeutic approaches. Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer. Here we review the application and status of precision medicine in GI cancer. Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy. With the introduction of gene panels including next-generation sequencing, it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer. Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors, novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs. These progressions will make it feasible to incorporate clinical, genome-based, and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.
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Affiliation(s)
- Tasuku Matsuoka
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
| | - Masakazu Yashiro
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
- Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan
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Elsaid A, Zahran R, Elshazli R, El-Sayed A, Abou Samra M, El-Tarapely F, Abdel-Malak C. Genetic polymorphisms of TP53 Arg72Pro and Pro47Ser among Egyptian patients with colorectal carcinoma. Arch Physiol Biochem 2019; 125:255-262. [PMID: 29560751 DOI: 10.1080/13813455.2018.1453522] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Previous reports demonstrated the role of TP53 gene polymorphisms with CRC risk among several ethnic populations. The purpose of this study is to assess the association of the TP53 Arg72Pro and Pro47Ser variants with CRC risk among Egyptian patients. SUBJECTS AND METHODS This work was conducted on 120 unrelated CRC Egyptian patients who were compared to 140 healthy controls. DNA was genotyped for these variants using the PCR-RFLP technique. RESULTS CRC patients observed a significant association of the rare genotype of TP53 Arg72Pro polymorphism compared with healthy controls. On the contrast, all genetic models showed no statistical association of TP53 Pro47Ser polymorphism among CRC patients compared with healthy controls. On the contrast, CRC patients of the TP53 gene polymorphisms indicated no significant difference regarding their clinical and laboratory markers. CONCLUSIONS Our findings indicate a strong association with TP53 Arg72Pro variant within increased risk of CRC among Egyptian patients.
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Affiliation(s)
- Afaf Elsaid
- a Genetics Unit, Children Hospital , Mansoura University , Mansoura , Egypt
| | - Rasha Zahran
- b Department of Biochemistry , College of Science, Damietta University , New Damietta , Egypt
| | - Rami Elshazli
- c Department of Biochemistry , College of Physical Therapy, Horus University in Egypt (HUE) , New Damietta , Egypt
| | - Ahmed El-Sayed
- d Department of Botany and Microbiology , College of Science, Damietta University , New Damietta , Egypt
| | - Marwa Abou Samra
- b Department of Biochemistry , College of Science, Damietta University , New Damietta , Egypt
| | - Fatma El-Tarapely
- b Department of Biochemistry , College of Science, Damietta University , New Damietta , Egypt
| | - Camelia Abdel-Malak
- b Department of Biochemistry , College of Science, Damietta University , New Damietta , Egypt
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Vitamin D receptor FokI polymorphism and the risks of colorectal cancer, inflammatory bowel disease, and colorectal adenoma. Sci Rep 2018; 8:12899. [PMID: 30150667 PMCID: PMC6110797 DOI: 10.1038/s41598-018-31244-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 08/10/2018] [Indexed: 02/08/2023] Open
Abstract
Based on an inverse association between vitamin D levels and the risks of colorectal diseases, a functional start codon polymorphism in the vitamin D receptor (VDR) gene is speculated to affect the risks for these diseases. To validate this hypothesis, we first conducted a case-control study of 695 colorectal cancer patients and 1,397 controls. The association of VDR FokI polymorphism with colorectal cancer risk was analyzed using a logistic regression model. In the present case-control study, compared to the F allele, the f allele seemed to be associated with lower risks of colon cancer and advanced colorectal cancer. Additionally, a meta-analysis of 27 studies was conducted to combine findings from previous studies investigating the association of FokI polymorphism with colorectal disease using a random effects model. In the present meta-analysis, the f allele was positively associated with the risk of inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. However, this allele was inversely associated with colon cancer and was not associated with the risk of rectal cancer or colorectal adenoma. In conclusion, the findings from this study imply that the role of VDR FokI polymorphism may differ based on the type and severity of colorectal disease.
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Tian X, Dai S, Sun J, Jiang S, Jiang Y. The association between the TP53 Arg72Pro polymorphism and colorectal cancer: An updated meta-analysis based on 32 studies. Oncotarget 2018; 8:1156-1165. [PMID: 27901479 PMCID: PMC5352043 DOI: 10.18632/oncotarget.13589] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 11/08/2016] [Indexed: 02/07/2023] Open
Abstract
Several previous studies evaluated the association between the Arg72Pro (rs1042522) polymorphism in the TP53 tumor suppressor gene and colorectal cancer (CRC). However, the results are conflicting. This meta-analysis aimed to shed new light on the precise association between TP53 variants and CRC. We analyzed 32 published case-control studies involving 8,586 cases and 10,275 controls using crude odd ratios (ORs) with 95% confidence intervals (CIs). The meta-analysis was performed using a fixed-effect or random-effects model, as appropriate. We found that the TP53 Arg72Pro polymorphism was not significantly associated with CRC risk in the overall population. However, subgroup analysis based on ethnicity revealed an increased risk of CRC among Asians (CC vs. GC+GG: OR=1.22, 95% CI: 1.02-1.45), and similar results were found for rectal cancer (CC vs. GC+GG: OR=1.34, 95% CI: 1.120-1.62). These results suggest that the TP53 Arg72Pro polymorphism CC genotype may contribute to an increased risk of CRC, especially for rectal cancer and among Asians.
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Affiliation(s)
- Xin Tian
- Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, 110001, PR China
| | - Shundong Dai
- Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, 110001, PR China.,Institute of Pathology and Pathophysiology, Shenyang, 110001, PR China
| | - Jing Sun
- Department of Immunology and Biotherapy, Liaoning Cancer Hospital and Institute, Shenyang, 110042, PR China
| | - Shenyi Jiang
- Department of Rheumatology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, PR China
| | - Youhong Jiang
- Molecular Oncology Laboratory of Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, 110001, PR China
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Pan Z, Chen M, Hu X, Wang H, Yang J, Zhang C, Pan F, Sun G. Associations between VDR gene polymorphisms and colorectal cancer susceptibility: an updated meta-analysis based on 39 case-control studies. Oncotarget 2018; 9:13068-13076. [PMID: 29560132 PMCID: PMC5849196 DOI: 10.18632/oncotarget.23964] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 11/14/2017] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Recent studies have reported the associations between vitamin D receptor (VDR) polymorphisms and colorectal cancer (CRC), but the results were not always consistent. This meta-analysis aims to evaluate whether VDR polymorphisms are associated with CRC susceptibility. MATERIALS AND METHODS Studies on the associations between VDR polymorphisms and CRC were retrieved from the Web of Science, PubMed, the Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese) databases. The odds ratio (OR) with 95% confidence intervals (CIs) was obtained. RESULTS Thirty-nine articles met all inclusion criteria and were included in the meta-analysis including 22101 CRC cases and 23696 healthy controls. The 39 articles consisted of five VDR gene polymorphisms including ApaI, FokI, BsmI, TaqI and Cdx2. The results of meta-analysis showed that the FokI polymorphism was on the fringe of statistically significant in the comparisons of F allele vs. f allele in fixed model (OR = 1.029, 95% CI = 0.999-1.059, Praw = 0.057, PFDR = 0.057). Moreover, for the associations between BsmI polymorphism with CRC, We observed significant differences in allele frequencies, the homozygous model and the dominant model between CRC patients and healthy controls (B vs. b: OR = 0.862, 95% CI = 0.761-0.976, Praw = 0.019, PFDR = 0.019; BB vs. bb: OR = 0.786, 95% CI = 0.636-0.972, Praw = 0.026, PFDR = 0.039; BB + Bb vs. bb: OR = 0.934, 95% CI = 0.888-0.982, Praw = 0.008, PFDR = 0.024, respectively). CONCLUSIONS This meta-analysis suggests that BsmI is associated with CRC risk and FokI might be a risk factor for CRC. However, these associations with CRC need further studied.
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Affiliation(s)
- Zhipeng Pan
- Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China
| | - Mengya Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
- The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Xingxing Hu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
- The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Hua Wang
- Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China
| | - Jiajia Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
- The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Congjun Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China
| | - Faming Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
- The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Guoping Sun
- Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, China
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de Lima JM, de Souza LG, da Silva IDCG, Forones NM. E-Cadherin and Metalloproteinase-1 and -7 Polymorphisms in Colorectal Cancer. Int J Biol Markers 2018; 24:99-106. [DOI: 10.1177/172460080902400206] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Purpose E-cadherin (CDH1) and metalloproteinase (MMP) polymorphisms could play a crucial role in cancer invasion. Our aim was to investigate the influence of the -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 polymorphisms on the frequency and progression of colorectal cancer (CRC). Experimental design A total of 130 patients with CRC and 130 noncancer controls were studied. The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results Patients with the 1G allele and a family history of CRC showed a six times higher risk of developing CRC (OR: 6.45, 95%CI: 2.02–20.6, p=0.001). The A/A CDH1 genotype was associated with a higher risk of metastatic disease (OR: 3.43, 95%CI: 1.27–9.27, p=0.023). A higher marginal risk of metastatic disease was observed for MMP-1 genotypes 1G/1G and 1G/2G (OR: 2.97, 95%CI: 0.93–9.47, p=0.098). Conclusions The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 single nucleotide polymorphisms did not modify the risk of CRC development. Patients with the 1G/1G or 1G/2G genotype and a family history of CRC presented a higher risk of CRC. The AA CDH1 and 1G/1G and 1G/2G MMP-1 genotypes might be associated with advanced metastatic disease, but are not markers of lymphatic metastasis.
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Affiliation(s)
- Jacqueline Miranda de Lima
- Oncology Group, Gastroenterology Division, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo - Brazil
| | - Lessileia Gomes de Souza
- Oncology Group, Gastroenterology Division, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo - Brazil
| | | | - Nora Manoukian Forones
- Oncology Group, Gastroenterology Division, Federal University of Sao Paulo (UNIFESP/EPM), Sao Paulo - Brazil
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Xie M, Zhao F, Zou X, Jin S, Xiong S. The association between CCND1 G870A polymorphism and colorectal cancer risk: A meta-analysis. Medicine (Baltimore) 2017; 96:e8269. [PMID: 29049220 PMCID: PMC5662386 DOI: 10.1097/md.0000000000008269] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND CyclinD1 (CCND1) is a key cell cycle regulatory protein. A large number of epidemiological studies have assessed the potential correlation between the CCND1 G870A polymorphism and the risk of colorectal cancer (CRC), but their findings have been inconsistent. To obtain a more precise understanding of the association between the G870A polymorphism in the CCND1 gene and the CRC risk, we conducted a more comprehensive meta-analysis. METHODOLOGY We searched PubMed, Ovid, Springer, Weipu, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering all publications (the last search was updated on January 10, 2017). The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. Statistical analyses were performed using Review Manager 5.3 and STATA 10.0 software. RESULTS A total of 7276 CRC patients and 9667 controls from 27 publications were included in this meta-analysis. We found that compared with GG homozygote genetic model, AA, AG, AA + AG genetic models of the CCND1 G870A polymorphism were significantly associated with overall CRC risk (AA homozygote genetic model: OR = 1.28, 95% CI = 1.10-1.49; AG heterozygote genetic model: OR = 1.15, 95% CI = 1.06-1.25; AA homozygote + AG heterozygote genetic model: OR = 1.19, 95% CI = 1.07-1.33). Subgroup analyses by ethnicity and cancer location showed that A carriers were consistently associated with a significantly increased risk of CRC in all subsets of participants (Asian and Caucasian; colon cancer and rectal cancer). When stratified by study design, we found a significant association in hospital-based studies (HB), but no significant associations were found in either population-based studies (PB) or family-based studies (FB). According to subgroup analysis by cancer type, the risk of sporadic colorectal cancer (sCRC) and hereditary nonpolyposis colorectal cancer (HNPCC) were not correlated with the CCND1 G870A polymorphism, except AG (AG vs GG: OR = 1.30, 95% CI = 1.11-1.53). CONCLUSIONS This meta-analysis suggests that the CCND1 G870A polymorphism is associated with an increased risk of CRC, especially that A carriers may be a major risk factor for CRC.
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Affiliation(s)
- Mei Xie
- Department of Oncology, Chengdu University of Traditional Chinese Medicine Affiliated Hospital
| | - Fen Zhao
- Department of Oncology, Chengdu First People's Hospital, Chengdu, Sichuan, China
| | - Xiaoling Zou
- Department of Oncology, Chengdu University of Traditional Chinese Medicine Affiliated Hospital
| | - Shuai Jin
- Department of Oncology, Chengdu University of Traditional Chinese Medicine Affiliated Hospital
| | - Shaoquan Xiong
- Department of Oncology, Chengdu University of Traditional Chinese Medicine Affiliated Hospital
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Cui X, Shen K, Xie Z, Liu T, Zhang H. Identification of key genes in colorectal cancer using random walk with restart. Mol Med Rep 2016; 15:867-872. [PMID: 28000901 DOI: 10.3892/mmr.2016.6058] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 11/15/2016] [Indexed: 11/05/2022] Open
Abstract
As the most common type of cancer and the second leading cause of cancer-associated mortality, colorectal cancer (CRC) has received increasing attention. The aim of the present study was to investigate the mechanisms of CRC by analyzing the microarray dataset, GSE32323. The GSE32323 dataset was downloaded from the Gene Expression Omnibus, and included 17 pairs of matched cancer and normal colorectal tissue samples. The differentially expressed genes (DEGs) were screened using the Linear Models for Microarray Data package and a search of CRC genes, also denoted as seed genes, was performed using the Online Mendelian Inheritance in Man database. Subsequently, the protein‑protein interaction (PPI) network was downloaded from the Search Tool for the Retrieval of Interacting Genes database and the sub‑network (CRC.PPI) of the DEGs and seed genes were obtained. In addition, the top 50 nodes with highest affinity scores in the CRC.PPI were identified using random walk with restart analysis. The potential functions of the DEGs included in the top 50 nodes were analyzed using the Database for Annotation, Visualization and Integrated Discovery online tool. Using the Drug Gene Interaction database, drug‑gene interaction analysis was performed to identify antineoplastic drug interacts with genes. A total of 1,640 DEGs between the CRC and normal samples were screened. The obtained seed genes included cyclin D1 (CCND1) and aurora kinase A (AURKA). The enriched functions for the 31 DEGs in the PPI network of the top 50 nodes were predominantly associated with cell cycle. The DEGs may function in CRC by interacting with other genes in the PPI network of the top 50 nodes, for example, DEP domain‑containing MTOR‑interacting protein (DEPTOR)‑CCND1, AURKA‑breast carcinoma amplified sequence‑1 (BCAS1), CCND1‑BCAS1, CCND1‑neural precursor cell expressed developmentally downregulated 9 (NEDD9) and CCND1‑mitogen‑activated protein kinase kinase 2 (MAP2K2). Only three DEGs (CCND1, AURKA and DEPTOR) had interactions with their corresponding antineoplastic drugs. Taken together, DEPTOR, AURKA, CCND1, BCAS1, NEDD9 and MAP2K2 may act in CRC.
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Affiliation(s)
- Xiaofeng Cui
- Department of Gastrointestinal Colorectal and Anal Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China
| | - Kexin Shen
- Department of Gastrointestinal Colorectal and Anal Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China
| | - Zhongshi Xie
- Department of Gastrointestinal Colorectal and Anal Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China
| | - Tongjun Liu
- Department of General Surgery, Jilin University, Changchun, Jilin 130022, P.R. China
| | - Haishan Zhang
- Department of Gastrointestinal Colorectal and Anal Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China
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16
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Qiu H, Cheng C, Wang Y, Kang M, Tang W, Chen S, Gu H, Liu C, Chen Y. Investigation of cyclin D1 rs9344 G>A polymorphism in colorectal cancer: a meta-analysis involving 13,642 subjects. Onco Targets Ther 2016; 9:6641-6650. [PMID: 27822068 PMCID: PMC5089821 DOI: 10.2147/ott.s116258] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The relationship between cyclin D1 (CCND1) rs9344 G>A polymorphism and colorectal cancer (CRC) risk is still ambiguous. To obtain a precise estimation of the relationship, we performed an extensive meta-analysis based on the eligible studies. Crude odds ratios with their 95% confidence intervals were harnessed to determine the strength of correlation between CCND1 rs9344 G>A polymorphism and CRC risk under the allele, the homozygote, the dominant, and the recessive genetic models, respectively (28 studies with 5,784 CRC cases and 7,858 controls). Our results indicated evidence of the association between CCND1 rs9344 G>A polymorphism and the increased risk of CRC in four genetic models: A vs G, AA vs GG, AA+GA vs GG, and AA vs GA+GG. In a stratified analysis by cancer type of CRC, there was an increased risk of sporadic CRC found in three genetic models: A vs G, AA vs GG, and AA+GA vs GG. In a stratified analysis by ethnicity, there was an increased CRC risk found among Asians in allele comparison genetic models, as well as Caucasians in two genetic models: AA+GA vs GG and A vs T. In summary, this meta-analysis demonstrates that CCND1 rs9344 G>A polymorphism may be a risk factor for CRC.
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Affiliation(s)
- Hao Qiu
- Department of Immunology, School of Medicine, Jiangsu University
| | - Chengguo Cheng
- Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang
| | - Yafeng Wang
- Department of Cardiology, The People's Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong
| | - Mingqiang Kang
- Department of Thoracic Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou
| | - Weifeng Tang
- Department of Thoracic Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou; Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang
| | - Shuchen Chen
- Department of Thoracic Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou
| | - Haiyong Gu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai
| | - Chao Liu
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang
| | - Yu Chen
- Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, People's Republic of China
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Xu XM, Ni XB, Yang GL, Luo ZG, Niu YM, Shen M. CCND1 G870A polymorphism and colorectal cancer risk: An updated meta-analysis. Mol Clin Oncol 2016; 4:1078-1084. [PMID: 27284448 DOI: 10.3892/mco.2016.844] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
Molecular epidemiological studies have revealed a closer association between cyclin D1 (CCND1) polymorphism and the risk of colorectal cancer; however, the results were inconsistent. The aim of the present meta-analysis was to investigate the association between CCND1 G870A polymorphism and colorectal cancer risk. Online electronic databases (PubMed and Embase) were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between CCND1 G870A polymorphism and the risk of colorectal cancer. In addition, heterogeneity, publication bias and sensitivity analysis were performed to guarantee the statistical power. In total, 23 published case-control studies with 6,320 patients and 8,252 controls were selected. Significantly increased risks were observed in four genetic models (A vs. G: OR=1.09, 95% CI=1.00-1.18, I2=54.3%; GA vs. GG: OR=1.13, 95% CI=1.04-1.24, I2=18.2%; AA vs. GG, OR=1.17: 95% CI=1.00-1.38, I2=52.5%; GA+AA vs. GG: OR=1.14, 95% CI=1.05-1.24, I2=33.8%). Similarly, significant associations were also identified in the stratified analysis in the cancer subtype of sporadic colorectal cancer (GA vs. GG: OR=1.21, 95% CI=1.04-1.42, I2=24.1%; GA+AA vs. GG: OR=1.18, 95% CI=1.02-1.37, I2=35.0%), Caucasian population (GA vs. GG, OR=1.14, 95% CI=1.02-1.28, I2=19.8%; GA+AA vs. GG, OR=1.14, 95% CI=1.02-1.27, I2=37.5%) and other subgroups of control design and genotyping type. The present updated meta-analysis suggested that CCND1 G870A may present an increased risk for developing colorectal cancer, particularly in sporadic colorectal cancer and a Caucasian population.
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Affiliation(s)
- Xiao-Ming Xu
- Department of Stomatology and Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China; Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Xiao-Bing Ni
- Department of Stomatology and Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China; Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Gong-Li Yang
- Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Zhi-Guo Luo
- Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Yu-Ming Niu
- Department of Stomatology and Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China; Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Ming Shen
- Jiangsu Key Laboratory of Oral Diseases, Department of Dental Implant, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
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18
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The significant association of CCND1 genotypes with colorectal cancer in Taiwan. Tumour Biol 2015; 36:6533-40. [PMID: 25809706 DOI: 10.1007/s13277-015-3347-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 03/16/2015] [Indexed: 01/30/2023] Open
Abstract
Colorectal cancer, one million cases of diagnosis worldwide annually, is one of the most common malignant tumors and 20 % incidence caused by low penetrance susceptibility genes. Cyclin D1 (CCND1) regulating cell cycle transition may determine the susceptible individuals to genomic instability and carcinogenesis. The study aimed at examining the contribution of CCND1 genotypes to colorectal cancer risk in Taiwan. The genotypes of CCND1 A870G (rs9344) and G1722C (rs678653) were determined among 362 colorectal cancer patients and 362 age- and gender-matched cancer-free controls. Significant differences were observed between colorectal cancer and control groups in the distributions of genotypic (P = 9.71 × 10(-4)) and allelic (P = 0.0017) frequencies at CCND1 A870G. Additionally, individuals carried AG or GG genotype had 0.56- or 0.51-fold higher of odds ratios for developing colorectal cancer than the AA genotype (95 % confidence intervals = 0.40-0.78 and 0.32-0.81, respectively). Furthermore, G allele of CCND1 A870G performed a protective effects for nonsmokers and nonalcohol drinkers (P = 0.0012 and 0.0007, respectively) on colorectal cancer risk. These findings support the concept that the cell cycle regulation may play a role in colorectal cancer initiation and development and CCND1 A870G genotyping maybe a feasible technology for colorectal cancer early detection.
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19
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Regulatory Variants and Disease: The E-Cadherin -160C/A SNP as an Example. Mol Biol Int 2014; 2014:967565. [PMID: 25276428 PMCID: PMC4167656 DOI: 10.1155/2014/967565] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 08/23/2014] [Accepted: 08/25/2014] [Indexed: 01/04/2023] Open
Abstract
Single nucleotide polymorphisms (SNPs) occurring in noncoding sequences have largely been ignored in genome-wide association studies (GWAS). Yet, amounting evidence suggests that many noncoding SNPs especially those that are in the vicinity of protein coding genes play important roles in shaping chromatin structure and regulate gene expression and, as such, are implicated in a wide variety of diseases. One of such regulatory SNPs (rSNPs) is the E-cadherin (CDH1) promoter -160C/A SNP (rs16260) which is known to affect E-cadherin promoter transcription by displacing transcription factor binding and has been extensively scrutinized for its association with several diseases especially malignancies. Findings from studying this SNP highlight important clinical relevance of rSNPs and justify their inclusion in future GWAS to identify novel disease causing SNPs.
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20
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Gnagnarella P, Pasquali E, Serrano D, Raimondi S, Disalvatore D, Gandini S. Vitamin D receptor polymorphism FokI and cancer risk: a comprehensive meta-analysis. Carcinogenesis 2014; 35:1913-9. [PMID: 25053622 DOI: 10.1093/carcin/bgu150] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Numerous studies investigated the associations of VDR polymorphisms with various types of cancer, suggesting an influence on cancer risk. FokI is one of the most frequently analysed polymorphisms but the results from single studies are contradictory. We performed a meta-analysis looking at the association between the FokI and all cancer sites and investigating sources of heterogeneity. We identified 77 independent studies up to April 2014. We presented the summary odds ratios (SORs) by cancer sites, ethnicity and study features. We found a significant association between FokI and ovarian cancer for ff genotype versus FF with no heterogeneity: SOR = 1.20 (95% CI: 1.02-1.41, I (2) = 0%). Moreover, we found a significant increased risk of any cancer: SOR = 1.08 (95% CI: 1.01-1.16, I (2) = 58%). A significant increased risk of any cancer is confirmed among Caucasian, among studies in Hardy-Weinberg equilibrium and nested case-control studies. Furthermore, among studies in Hardy-Weinberg equilibrium, skin cancer was found significantly associated with FokI: SOR = 1.24 (95% CI: 1.01-1.54; I (2) = 24%) for ff versus FF. The estimated number of cases attributable to ff genotype is 4221 for ovarian cancer and 52858 for skin cancer worldwide each year. No indication for publication bias was found for any cancer site. In conclusion, we found an overall significant association of FokI polymorphism with any cancer, with differential effect by ethnicity. In particular, the summary estimates indicate an increase risk for ovarian and skin cancer for ff versus FF. However, other factors may act modifying the association, and further studies are needed to clarify the impact on cancer risk.
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Affiliation(s)
- Patrizia Gnagnarella
- Division of Epidemiology and Biostatistics and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan 20141, Italy
| | - Elena Pasquali
- Division of Epidemiology and Biostatistics and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan 20141, Italy
| | - Davide Serrano
- Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan 20141, Italy
| | - Sara Raimondi
- Division of Epidemiology and Biostatistics and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan 20141, Italy
| | - Davide Disalvatore
- Division of Epidemiology and Biostatistics and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan 20141, Italy
| | - Sara Gandini
- Division of Epidemiology and Biostatistics and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan 20141, Italy
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Li YX, Lu Y, Li CY, Yuan P, Lin SS. Role of CDH1 promoter methylation in colorectal carcinogenesis: a meta-analysis. DNA Cell Biol 2014; 33:455-62. [PMID: 24684676 DOI: 10.1089/dna.2013.2291] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
This meta-analysis was performed to evaluate the role of CDH1 promoter methylation in colorectal carcinogenesis. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Nine clinical cohort studies met all our inclusion criteria and were included in this meta-analysis. A total of 883 colorectal cancer (CRC) patients were assessed. Our meta-analysis results revealed that the frequencies of CDH1 promoter methylation in CRC tissues were higher than those in control tissues (OR=2.61, 95% CI=1.24-5.50, p=0.012). A subgroup analysis by ethnicity showed that CDH1 promoter methylation was closely linked to the pathogenesis of CRC among Asians and Africans (Asians: OR=2.90, 95% CI=1.26-6.67, p=0.012; Africans: OR=3.81, 95% CI=1.56-9.34, p=0.003; respectively), but not among Caucasians (OR=1.68, 95% CI=0.24-11.72, p=0.598). A further subgroup analysis by type of control tissues suggested that CRC tissues also exhibited higher frequencies of CDH1 promoter methylation than those of normal and adjacent tissues (normal: OR=1.57, 95% CI=1.12-2.21, p=0.009; adjacent: OR=5.07, 95% CI=2.91-8.82, p<0.001; respectively). However, we found no evidence for any significant difference in the frequencies of CDH1 promoter methylation between CRC tissues and adenomas tissues (OR=1.18, 95% CI=0.74-1.90, p=0.485). Our findings provide empirical evidence that CDH1 promoter methylation may play an important role in colorectal carcinogenesis. Thus, CDH1 promoter methylation may be a useful biomarker for the early diagnosis of CRC.
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Affiliation(s)
- Yu-Xi Li
- Department of Coloproctological, The Fourth Affiliated Hospital of China Medical University , Shenyang, People's Republic of China
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TP53 alterations and colorectal cancer predisposition in south Indian population: A case-control study. Tumour Biol 2013; 35:2303-11. [DOI: 10.1007/s13277-013-1305-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Accepted: 10/08/2013] [Indexed: 10/26/2022] Open
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Cyclin D1 G870A polymorphism and risk of nasopharyngeal carcinoma: a meta-analysis. ScientificWorldJournal 2013; 2013:689048. [PMID: 24222746 PMCID: PMC3814096 DOI: 10.1155/2013/689048] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Accepted: 09/01/2013] [Indexed: 12/28/2022] Open
Abstract
Recently, there have been a number of studies on the association between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between cyclin D1 G870A polymorphism and the risk of nasopharyngeal carcinoma. No significant association was found between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Caucasian subgroup, and no significant association in any genetic models among Asians was observed. In summary, positive results have been shown on the search for polymorphic variants influencing the risk of NPC. This meta-analysis provides evidence of the association between CCND1 G870A polymorphism and NPC risk, supporting the hypothesis that CCND1 870A allele probably acts as an important NPC protective factor in Caucasians but not in Asians. Since the results of our meta-analysis are preliminary and may be biased by the relatively small number of subjects, they still need to be validated by well-designed studies using larger samples in the future.
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Zhou C, An H, Hu M, Liu Q, Geng P, Xu J, Sun B, Liu C. The cyclin D1 (CCND1) G870A polymorphism and lung cancer susceptibility: a meta-analysis. Tumour Biol 2013; 34:3831-7. [PMID: 23873109 DOI: 10.1007/s13277-013-0968-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 06/24/2013] [Indexed: 01/10/2023] Open
Abstract
Several studies have investigated the association between Cyclin D1 (CCND1) G870A genetic polymorphism and lung cancer susceptibility, but the results were inconclusive. The aim of this meta-analysis was to summarize available evidence for such a relationship. The reviewers made use of MEDLINE, EMBASE, and BIOSIS databases. The relevant data were independently extracted by two reviewers. The odds ratio (OR) with 95% confidence interval (CI) was selected as the principal outcome measure. The heterogeneity test, the publication bias test, and the sensitivity analysis were performed. Overall, a total of 10 case-control studies were included. Our meta-analysis indicated that CCND1 G870A genetic polymorphism was a risk factor for lung cancer under homozygote model (OR = 1.18; 95% CI = 1.02, 1.37), recessive model (OR = 1.21; 95% CI = 1.03, 1.41), and allele model (OR = 1.11; 95% CI = 1.02, 1.21). In the subgroup analysis by source of ethnicity, a statistical increase of lung cancer risk was found among Asian groups for allele model (OR = 1.11; 95% CI = 1.01-1.22). The present meta-analysis suggests that CCND1 G870A polymorphism may be a risk factor for lung cancer. Besides, allele A may contribute to increased lung cancer risk.
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Affiliation(s)
- Changxi Zhou
- Nanlou Respiratory Diseases Department, PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People's Republic of China
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Synchronous appendiceal and intramucosal gastric signet ring cell carcinomas in an individual with CDH1-associated hereditary diffuse gastric carcinoma: a case report of a novel association and review of the literature. BMC Gastroenterol 2013; 13:114. [PMID: 23849133 PMCID: PMC3716915 DOI: 10.1186/1471-230x-13-114] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Accepted: 07/10/2013] [Indexed: 02/08/2023] Open
Abstract
Background Hereditary diffuse gastric carcinoma is an autosomal dominant cancer syndrome associated with mutations of the E-cadherin gene (CDH1). E-cadherin is normally involved in cell-cell adhesion, so it not surprising that individuals with this syndrome are predisposed to develop malignancies with dyshesive morphologies at a young age, such as diffuse (signet ring cell) gastric carcinoma and lobular breast carcinoma. Herein we describe the first reported case of primary appendiceal signet ring cell carcinoma arising in a CDH1-associated hereditary diffuse gastric carcinoma kindred with synchronous primary diffuse gastric carcinoma. Case presentation A 51- year old woman, with known CDH1 mutation carrier status and a prior history of lobular breast carcinoma underwent prophylactic total gastrectomy which revealed multifocal intramucosal signet ring cell carcinoma. An appendectomy was performed at the same time due to a prior episode of presumed appendicitis, with pathologic examination significant for a primary signet ring cell carcinoma of the appendix. Conclusion As appendiceal signet ring cell carcinoma is exceedingly rare, the occurrence of this neoplasm in this patient, with this particular morphology, provides credence for it being part of the hereditary diffuse gastric carcinoma spectrum of malignancies.
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Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer. J Hum Genet 2012; 57:709-716. [PMID: 22875147 DOI: 10.1038/jhg.2012.99] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Some 15-20% of multiple adenomatous polyposis have no genetic explanation and 20-30% of colorectal cancer (CRC) cases are thought to be due to inherited multifactorial causes. Accumulation of deleterious effects of low-frequency dominant and independently acting variants may be a partial explanation for such patients. The aim of this study was to type a selection of rare and low-frequency variants (<5%) to elucidate their role in CRC susceptibility. A total of 1181 subjects were included (866 controls; 315 cases). Cases comprised UK (n=184) and French (n=131) patients with MAP (n=187) or early-onset CRC (n=128). Seventy variants in 17 genes were examined in cases and controls. The effect of the variant effect on protein function was investigated in silico. Out of the 70 variants typed, 36 (51%) were tested for association. Twenty-one variants were rare (minor allele frequency (MAF) <1%). Four rare variants were found to have a significantly higher MAF in cases (EXO1-12, MLH1-1, CTNNB1-1 and BRCA2-37, P<0.05) than in controls. Pooling all rare variants with a MAF <0.5% showed an excess risk in cases (odds ratio=3.2; 95% confidence interval=1.1-9.5; P=0.04). Rare variants are important risk factors in CRC and, as such, should be systematically assayed alongside common variation in the search for the genetic basis of complex diseases.
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Contribution of the -160C/A polymorphism in the E-cadherin promoter to cancer risk: a meta-analysis of 47 case-control studies. PLoS One 2012; 7:e40219. [PMID: 22792244 PMCID: PMC3390351 DOI: 10.1371/journal.pone.0040219] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2012] [Accepted: 06/02/2012] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The -160C/A polymorphism (rs16260) of E-cadherin, a tumor repressor gene, has been shown to be a tumor susceptibility allele for various types of cancers. Because the significance of this polymorphism to cancer risk has been recognized, there are increasing studies investigating -160C/A in different types of cancers and ethnic populations. However, there is still uncertainty about the level of risk for a variety of cancers. METHODS To resolve the controversial question raised by these studies as of March 2012 and provide more statistical power for detecting the significance of -160C/A, we performed a meta-analysis of 47 case-control studies in 16 types of cancers (18,194 cases and 20,207 controls). A meta-regression model and subgroup analysis were employed to identify the source of heterogeneity. Publication bias was evaluated, and sensitivity analysis and cumulative evidence assessment were also performed. RESULTS Using fixed- and random-effects models, the -160AA homozygote was more susceptible to urothelial cancer compared with the -160CA heterozygote. Additionally, the -160A allele is an ethnicity-dependent risk factor for prostate and colorectal cancers. Carriers of the -160A allele in Asians and Europeans were more susceptible to prostate cancer, whereas their North American counterparts seemed tolerant. The -160AA homozygote plays a protective role for Europeans who develop colorectal cancer. The stability of these observations was confirmed by a one-way sensitivity analysis. However, the cumulative evidence for all cancer types was considered 'weak' using the Venice guidelines. CONCLUSIONS A meta-analysis indicated that the -160A allele of E-cadherin provides a higher risk for the development of prostate and urothelial cancers and a protective role for colorectal cancer in an ethnicity-dependent manner.
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Naccarati A, Polakova V, Pardini B, Vodickova L, Hemminki K, Kumar R, Vodicka P. Mutations and polymorphisms in TP53 gene--an overview on the role in colorectal cancer. Mutagenesis 2012; 27:211-8. [PMID: 22294769 DOI: 10.1093/mutage/ger067] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
A functionally normal TP53 is essential to protect organisms from developing cancer. Somatic mutations in the gene represent one of the highest recurring perturbations in human tumours, including colorectal cancer (CRC). However, the variegated phenotype of wide spectrum of somatic mutations in TP53 and the complexity of the disease prevent a straight interpretation of the mutational analysis in tumours. In addition to the presence of somatic mutations, polymorphic features of the gene may also contribute to alteration of the normal TP53 functioning and variants, mainly in the form of single nucleotide polymorphisms, can be expected to impact susceptibility to sporadic CRC. In the present study, we reviewed the potential role of alterations in the TP53 gene, both somatic mutations and inherited sequence variations, in predisposition to CRC and in the prognosis and response to therapy. The available data from association studies have mostly shown contradictory outcomes. The majority of the studies were based on limited sample sizes and focussed on a limited number of polymorphisms, with main being the rs1042522 (Arg72Pro). Thus far, there is no possible generalisation of the role of TP53 as also a predictor of therapeutic response and prognosis. The effects of TP53, and its abnormalities, on the response of tumours to cytotoxic drugs, radiation and chemoradiation are complex. However, from studies it is emerging that the inherited genetics of TP53 pathway components could be utilised to further define patient populations in their abilities to induce p53 activity in response to either DNA damaging or p53-targeted therapies.
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Affiliation(s)
- A Naccarati
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Videnska 1083, 14200 Prague 4, Czech Republic.
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Yang Y, Wang F, Shi C, Zou Y, Qin H, Ma Y. Cyclin D1 G870A polymorphism contributes to colorectal cancer susceptibility: evidence from a systematic review of 22 case-control studies. PLoS One 2012; 7:e36813. [PMID: 22606291 PMCID: PMC3350479 DOI: 10.1371/journal.pone.0036813] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Accepted: 04/06/2012] [Indexed: 12/20/2022] Open
Abstract
Background Cyclin D1 (CCND1) plays a vital role in cancer cell cycle progression. Numerous epidemiological studies have evaluated the association between the CCND1 G870A polymorphism and the risk of colorectal cancer. However, these studies have yielded conflicting results. To derive a more precise estimation of this association, we conducted a meta-analysis and systematic review. Methodology/Principal Findings A comprehensive search was conducted to identify eligible studies of the CCND1 G870A polymorphism and colorectal cancer risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model. We applied a grading system (Venice criteria) that assessed the epidemiological strength of the association. A total of 22 publications that included 6157 cases and 8198 controls were identified. We found that the CCND1 G870A polymorphism was significantly associated with overall colorectal cancer risk (homozygote genetic model: OR = 1.130, 95% CI = 1.023–1.248, P = 0.016; heterozygote genetic model: OR = 1.124, 95% CI = 1.030–1.226, P = 0.009; dominant genetic model: OR = 1.127, 95% CI = 1.037–1.224, P = 0.005). After further stratified analyses, the increased risk was observed only in the subgroups of hospital-based studies, PCR-RFLP genotyping methods, sporadic colorectal cancer, and Caucasian ethnicity. Conclusions The available evidence demonstrates that the CCND1 870A allele might be a low-penetrant risk factor for colorectal cancer.
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Affiliation(s)
- Yongzhi Yang
- Department of Surgery, Shanghai Tenth People’s Hospital affiliated with Tongji University, Shanghai, People’s Republic of China
- Department of Surgery, The Sixth People’s Hospital affiliated with Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Feng Wang
- Department of Surgery, Shanghai Tenth People’s Hospital affiliated with Tongji University, Shanghai, People’s Republic of China
| | - Chenzhang Shi
- Department of Surgery, The Sixth People’s Hospital affiliated with Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Yang Zou
- Department of Surgery, The Sixth People’s Hospital affiliated with Shanghai Jiao Tong University, Shanghai, People’s Republic of China
| | - Huanlong Qin
- Department of Surgery, Shanghai Tenth People’s Hospital affiliated with Tongji University, Shanghai, People’s Republic of China
- * E-mail: (YLM); (HLQ)
| | - Yanlei Ma
- Department of Surgery, Shanghai Tenth People’s Hospital affiliated with Tongji University, Shanghai, People’s Republic of China
- * E-mail: (YLM); (HLQ)
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Bai YH, Lu H, Hong D, Lin CC, Yu Z, Chen BC. Vitamin D receptor gene polymorphisms and colorectal cancer risk: a systematic meta-analysis. World J Gastroenterol 2012; 18:1672-9. [PMID: 22529698 PMCID: PMC3325535 DOI: 10.3748/wjg.v18.i14.1672] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2011] [Revised: 02/22/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the relationship between polymorphisms present in the vitamin D receptor (VDR) gene and colorectal cancer risk, a systematic meta-analysis of population-based studies was performed. METHODS A total of 38 relevant reports published between January 1990 and August 2010 were identified, of which only 23 qualified for this meta-analysis based on our selection criteria. Five polymorphic variants of the VDR gene, including Cdx-2 (intron 1e) and FokI (exon 2) present in the 5' region of the gene, and BsmI (intron 8), ApaI (intron 8), and TaqI (exon 9) sites present in the 3' untranslated region (UTR), were evaluated for possible associations with colorectal cancer risk. Review manager 4.2 was used to perform statistical analyses. RESULTS In the meta-analysis performed, only the BsmI polymorphism was found to be associated with colorectal cancer risk. In particular, the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb: odds ratio (OR) = 0.87, 95% CI: 0.80-0.94, P = 3 × 10(-4); BB vs Bb + bb: OR = 0.90, 95% CI: 0.84-0.97, P = 5 × 10(-4)]. Moreover, in subgroup analyses, the BsmI B genotype was significantly associated with colon cancer, and not rectal cancer. An absence of between-study heterogeneity was also observed. CONCLUSION A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.
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Yang J, Zhang G, Chen J. CCND1 G870A polymorphism is associated with increased risk of colorectal cancer, especially for sporadic colorectal cancer and in Caucasians: a meta-analysis. Clin Res Hepatol Gastroenterol 2012; 36:169-77. [PMID: 22322158 DOI: 10.1016/j.clinre.2011.11.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Revised: 11/10/2011] [Accepted: 11/25/2011] [Indexed: 02/04/2023]
Abstract
AIMS To detect the association between G870A polymorphism of cyclin D1 (CCND1) gene and colorectal cancer. METHODS We performed a systematic literature and abstract search using PubMed, EMBase digital database. Keywords included CCND1, cyclin D1, polymorphism, SNP, colon cancer, rectal cancer and colorectal cancer. "And", "OR" and "NOT" were used as conjunction to narrow and widen the search. Data were extracted by two investigators independently, and meta-analysis was carried out by using Review Manager 4.2.8. The following pairwised combinations of genotypes for the CCND1 G870A polymorphism were evaluated: AA vs. GG, AG vs. GG, AA+AG vs. GG. Subsequently, sub-group analyses for cancer type, ethnicity, and the family history were performed. Sensitivity analysis was conducted by excluding the articles deviated from Hardy-Weinberg equilibrium. RESULTS Using GG genotype as a reference, A carriers were associated with a significantly increased cancer risk (OR=1.15, 95%CI=1.06-1.25, P=0.001, P(heterogeneity)=0.130), especially with rectal cancer (OR=1.24, 95%CI=1.02-1.51, P=0.030, P(heterogeneity)=0.570) and sporadic colorectal cancer (OR=1.26, 95%CI=1.08-1.46, P=0.003, P(heterogeneity)=0.730). The effect of A carriers on cancer also existed in Caucasians (OR=1.19, 95%CI=1.06-1.32, P=0.002, P(heterogeneity)=0.100). CONCLUSIONS CCND1 G870A polymorphism is associated with the increased risk of colorectal cancer, especially for sporadic colorectal cancer and in Caucasians.
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Affiliation(s)
- Jing Yang
- Department of gastroenterology, the Third Affiliated Hospital of Suzhou University, Changzhou, China.
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Geng P, Chen Y, Ou J, Yin X, Sa R, Liang H. The E-cadherin (CDH1) -C160A polymorphism and colorectal cancer susceptibility: a meta-analysis. DNA Cell Biol 2012; 31:1070-7. [PMID: 22339265 DOI: 10.1089/dna.2011.1380] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
E-cadherin, encoded by the CDH1 gene, involves in invasion and metastasis of cancer cells. CDH1 -C160A polymorphism was shown to contribute to genetic susceptibility to colorectal cancer (CRC). However, the results from different studies remain controversial. This study was conducted to further explore the association between CDH1 -C160A genetic polymorphism and CRC susceptibility by means of a meta-analysis. A comprehensive literature search was conducted to identify all case-control studies of CDH1 -C160A polymorphism and risk for CRC. A total of nine eligible studies, including 7954 CRC cases and 7369 controls, were identified to the meta-analysis. On the whole, the meta-analysis indicated that CDH1 -C160A genetic polymorphism could reduce the risk of CRC under AA versus CC contrast (odds ratio [OR]=0.86, 95% confidence interval [CI]=0.75-0.98, p(heterogeneity)=0.11), recessive model (OR=0.88, 95% CI=0.77-0.99, p(heterogeneity)=0.23), dominant model (OR=0.92, 95% CI=0.87-0.99, p(heterogeneity)=0.11), and allele A versus allele C contrast (OR=0.93, 95% CI=0.88-0.98, p(heterogeneity)=0.26). A conclusion could be drawn from the research that CDH1 -C160A polymorphism provides a possible protection against CRC, which is especially evident in Caucasian and hospital populations.
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Affiliation(s)
- Peiliang Geng
- Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, PR China
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Wang Y, Yang H, Li L, Wang H, Zhang C, Xia X. E-cadherin (CDH1) gene promoter polymorphism and the risk of colorectal cancer : a meta-analysis. Int J Colorectal Dis 2012; 27:151-8. [PMID: 21997289 DOI: 10.1007/s00384-011-1320-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/04/2011] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Published data on the relationship between E-cadherin (CDH1) gene promoter polymorphisms and colorectal cancer (CRC) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was carried out. METHODS In this meta-analysis, we evaluated reported studies of associations between polymorphisms of CDH1 gene promoter -160 C > A and -347 G > GA site, and CRC risk using fixed-effects model and random-effects model. RESULTS We found decreased CRC risk among subjects carrying CDH1 -160AA (odds ratio [OR] = 0.86, 95 percent confidence interval [95% CI]: 0.75-0.98) and CA + AA (OR = 0.92, 95% CI: 0.87-0.98), using 4,652/4,428 cases/controls and 7,866/7,689 cases/controls from ten studies, respectively. We found a protective effect of the CDH1 -160CA + AA polymorphisms for CRC in distal site tumor population and population-based control in stratified analysis. We found a protective effect of the CDH1 -160AA and CA + AA polymorphisms for CRC in European and American population (OR = 0.87, 95% CI: 0.76-0.99 and OR = 0.91, 95% CI: 0.85-0.98, respectively). We observed that the CDH1 -347 G/GA + GA/GA carrier had an increased risk of CRC, the summary OR was 1.33 (95% CI: 1.08-1.62). CONCLUSIONS Data indicated that certain CDH1 gene promoter -160 C > A and -347 G > GA variants might affect the susceptibility of CRC. Recommendations for further studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.
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Affiliation(s)
- Yadong Wang
- Henan Center for Disease Control and Prevention, No. 105 of East Nongye Road, Zhengdong New Area, 450016, Zhengzhou, China.
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Zhang LQ, Wang J, Shang JQ, Bai JL, Liu FY, Guan X, Zhou JN. Cyclin D1 G870A polymorphism and colorectal cancer susceptibility: a meta-analysis of 20 populations. Int J Colorectal Dis 2011; 26:1249-1255. [PMID: 21544737 DOI: 10.1007/s00384-011-1220-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/19/2011] [Indexed: 02/04/2023]
Abstract
PURPOSE Studies investigating the association between genetic polymorphism of cyclin D1 (CCND1) G870A and risk of colorectal cancer (CRC) reported conflicting results. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. MATERIALS AND METHODS We performed an extensive search of relevant studies and carried out a meta-analysis, including 20 studies with 5,975 cases and 8,333 controls, to obtain a more precise estimate. RESULTS Overall, significantly elevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs. GG: OR = 1.23, 95% CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95% CI = 1.01-1.26; dominant model: OR = 1.16, 95% CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected among Caucasians (AA vs. GG: OR = 1.27, 95% CI = 1.04-1.44; dominant model: OR = 1.17, 95% CI = 1.02-1.34).We also observed sporadic CRC with an increased cancer susceptibility (AA vs. GG: OR = 1.24, 95% CI = 1.04-1.48; dominant model: OR = 1.17, 95% CI = 1.04-1.33), when colorectal cancer was stratified into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC). However, no significant associations were found in both Asians and HNPCC patients for all genetic models. CONCLUSION Result suggests that the cyclin D1 870A allele is a low-penetrant risk factor for developing sporadic colorectal cancer, especially among Caucasians.
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Affiliation(s)
- Lou-Qian Zhang
- Department of Medical Oncology, Affiliated Cancer Hospital, Nanjing Medical University, Nanjing, China
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Cyclin D1 (CCND1) G870A gene polymorphism is an ethnicity-dependent risk factor for digestive tract cancers: a meta-analysis comprising 20,271 subjects. Cancer Epidemiol 2011; 36:106-15. [PMID: 21606015 DOI: 10.1016/j.canep.2011.04.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2011] [Revised: 04/14/2011] [Accepted: 04/20/2011] [Indexed: 02/05/2023]
Abstract
Published data on the association between Cyclin D1 (CCND1) G870A gene polymorphism and digestive tract cancers (DTC) are inconclusive. We carried out a meta-analysis of published case-control studies to derive a more precise estimation of the association. Relevant studies were identified from PubMed, EMBASE, and China National Knowledge Infrastructure up to February 1st, 2011. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to investigate the strength of the association. Data were available from a total of 33 case-control studies with 8534 cases and 11,737 controls. The combined results based on all studies showed that there was a statistically significant link between CCND1 G870A polymorphism and DTC risk (GG vs. AA: OR=0.83, 95%CI=0.71-0.96). In the analysis of ethnic groups, we found the A allele carriers had a significantly increased DTC susceptibility among Caucasians, but not among Asians. When stratified for tumor location, the results based on all studies only showed the variant allele 870A might have a significantly increased risk of colorectal cancer (CRC), especially of rectal cancer (GG vs. AA: OR=0.71, 95%CI=0.58-0.89). When stratifying by the stage and histological differentiation of CRC, we only observed that patients had a significantly higher frequency of CCND1 870 AA than non-cancer patients among Caucasians. The A allele carriers (hetero- or homozygotes) were significantly more common in cases with a family history of CRC than in controls. There was no evidence of publication bias for CCND1 G870A polymorphism with DTC risk. In summary, this meta-analysis demonstrates that the CCND1 G870A polymorphism may be an ethnicity-dependent risk factor for DTC. And this genetic variant may increase the risk of rectal cancer, but not colon cancer.
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Touvier M, Chan DSM, Lau R, Aune D, Vieira R, Greenwood DC, Kampman E, Riboli E, Hercberg S, Norat T. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2011; 20:1003-16. [PMID: 21378269 DOI: 10.1158/1055-9965.epi-10-1141] [Citation(s) in RCA: 158] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Our objective was to conduct a systematic review and meta-analysis of prospective studies on colorectal cancer (CRC) and vitamin D intake and 25-hydroxyvitamin D status, as part of the World Cancer Research Fund Continuous Update Project. We also aimed at conducting meta-analysis of all studies on CRC and vitamin D receptor (VDR) single-nucleotide polymorphisms. METHODS Relevant studies were identified in PubMed (up to June 2010). Inclusion criteria were original and peer-reviewed publications with a prospective design (for studies on vitamin D intake or status). Random effects of dose-response meta-analyses were performed on cancer incidence. RESULTS We observed inverse associations of CRC risk with dietary vitamin D [summary relative risk (RR) per 100 IU/day = 0.95, 95% CI: 0.93-0.98; 10 studies; range of intake (midpoints) = 39-719 IU/day] and serum/plasma 25-hydroxyvitamin D (RR per 100 IU/L = 0.96, 0.94-0.97; 6 studies; range = 200-1,800 IU/L), but not with total vitamin D (5 studies). Supplemental (2 studies; range = 0-600 IU/day) and total (4 studies; range = 79-732 IU/day) vitamin D intake and 25-hydroxyvitamin D status (6 studies; range = 200-1,800 IU/L) were inversely associated with colon cancer risk. We did not observe statistically significant associations between FokI, PolyA, TaqI, Cdx2, and ApaI VDR polymorphisms and CRC risk. The BsmI polymorphism was associated with a lower CRC risk (RR = 0.57, 0.36-0.89 for BB versus bb, 8 studies). CONCLUSIONS These meta-analyses support the evidence of an inverse association between vitamin D intake, 25-hydroxyvitamin D status, and the BsmI VDR polymorphism and CRC risk. IMPACT Improving vitamin D status could be potentially beneficial against CRC incidence.
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Affiliation(s)
- Mathilde Touvier
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
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Economopoulos K, Sergentanis T. Methodological remarks concerning the recent meta-analysis on p53 codon 72 polymorphism and colorectal cancer risk. Eur J Surg Oncol 2010; 36:1225-6; author reply 1227-8. [DOI: 10.1016/j.ejso.2010.09.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2010] [Revised: 07/14/2010] [Accepted: 09/21/2010] [Indexed: 11/26/2022] Open
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Tang NP. Response to letter to editor entitled “Methodological remarks concerning the recent meta-analysis on p53 codon 72 polymorphism and colorectal cancer risk”. Eur J Surg Oncol 2010. [DOI: 10.1016/j.ejso.2010.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Bonilla C, Lefèvre JH, Winney B, Johnstone E, Tonks S, Colas C, Day T, Hutnik K, Boumertit A, Midgley R, Kerr D, Parc Y, Bodmer WF. Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patients. J Hum Genet 2010; 56:58-63. [PMID: 21107342 DOI: 10.1038/jhg.2010.144] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
We examined the influence that rare variants and low-frequency polymorphisms in the cancer candidate gene CCND1 have on the development of multiple intestinal adenomas and the early onset of colorectal cancer. Individuals with <100 multiple polyps and patients with colorectal cancer diagnosed before 50 years of age were recruited in UK, and screened for sequence changes in the coding and regulatory regions of CCND1. A set of about 800 UK control individuals was genotyped for the variants discovered in the cases. Variants in the promoter, intron-exon boundaries and untranslated regions of the CCND1 gene had higher frequencies in cases than in controls. Five of these variants were typed in a set of French multiple adenoma and early-onset patients, who also showed higher allele frequencies than UK controls. When pooled together, variants with frequencies lower than 1% conferred an increased risk of disease that was significant in the multiple adenoma group (odds ratio (OR) 2.2; 95% confidence interval, 1.1-4.4; P = 0.03). Most variants had a putative functional effect when assessed in silico. We conclude that rare variants of CCND1 are risk factors for colorectal cancer, with considerably larger effects than common polymorphisms, and as such should be systematically evaluated in susceptibility studies.
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Affiliation(s)
- Carolina Bonilla
- Department of Clinical Pharmacology, University of Oxford, Headington, Oxford, UK
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Dahabreh IJ, Linardou H, Bouzika P, Varvarigou V, Murray S. TP53 Arg72Pro polymorphism and colorectal cancer risk: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2010; 19:1840-7. [PMID: 20615891 DOI: 10.1158/1055-9965.epi-10-0156] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The TP53 rs1042522 polymorphism (c.215C>G, Arg72Pro) has been extensively investigated as a potential risk factor for colorectal cancer, but the results have thus far been inconclusive. METHODS We searched multiple electronic databases to identify studies investigating the association between the Arg72Pro polymorphism and colorectal cancer. Individual study odds ratios (OR) and their confidence intervals were estimated using allele-frequency, recessive, and dominant genetic models. Summary ORs where estimated using random effects models. RESULTS We identified 23 eligible case-control studies, investigating 6,514 cases and 9,334 controls. There was significant between-study heterogeneity for all genetic models. The control group in one of the studies was not in Hardy-Weinberg equilibrium; only three studies reported that genotyping was blinded to case/control status and five studies used tumor tissue for case genotyping. Overall, we did not identify any association between rs1042522 and colorectal cancer risk under an allele-frequency comparison (OR, 0.99; 95% confidence interval, 0.89-1.09). Likewise, no association was evident under dominant or recessive models. Studies using tumor tissue for case genotyping found a protective effect for the Pro allele, compared with studies using somatic DNA (P(interaction) = 0.03). Results were also inconsistent between different genotyping methods (P(interaction) = 0.03). CONCLUSION We did not identify an association between TP53 rs1042522 and colorectal cancer. Published results seem to be driven by technical artifacts rather than true biological effects. IMPACT Future genetic association studies should use more rigorous genotyping methods and avoid the use of tumor tissue as a source of DNA to prevent genotype misclassification due to loss of heterozygosity.
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Affiliation(s)
- Issa J Dahabreh
- Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 35 Kneeland Street, Boston, MA 02111, USA.
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Zambirinis CP, Theodoropoulos G, Gazouli M. Undefined familial colorectal cancer. World J Gastrointest Oncol 2009; 1:12-20. [PMID: 21160768 PMCID: PMC2999090 DOI: 10.4251/wjgo.v1.i1.12] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2009] [Revised: 03/31/2009] [Accepted: 04/07/2009] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC), one of the most common cancers of the world, is actually a spectrum of several subtypes, with different molecular profiles, clinico-pathological characteristics and possibly separate pathways of progression. It is estimated that in approximately 25%-35% of cases, a familial component exists, so they are classified as familial CRC (fCRC). However the known hereditary CRC syndromes justify only up to 5%. The rest are attributed to some inherited genetic predisposition passed to offspring through low-penetrance genes, which in the proper environmental setting can bring on tumorigenesis. Furthermore, part of the familial clustering may be attributed to chance. Because of the complexity regarding the etiology of CRC, the clinician is sometimes faced with obscure patient data, and cannot be sure if they are dealing with fCRC or sporadic CRC. The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis, classification and treatment of CRC, but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.
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Affiliation(s)
- Constantinos Pantelis Zambirinis
- Constantinos Pantelis Zambirinis, First Propaedeutic Surgical Department, Hippocration University Hospital, School of Medicine, University of Athens, 11527 Athens, Greece
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Pittman AM, Twiss P, Broderick P, Lubbe S, Chandler I, Penegar S, Houlston RS. The CDH1-160C>A polymorphism is a risk factor for colorectal cancer. Int J Cancer 2009; 125:1622-5. [PMID: 19569232 DOI: 10.1002/ijc.24542] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Part of the inherited susceptibility to colorectal cancer (CRC) is caused by the coinheritance of common low risk variants. E-cadherin (CDH1) has an established role in CRC; somatic inactivation of CDH1 is a common early event, and germline mutations can cause early-onset CRC. The -160C>A promoter variant (rs16260) of CDH1 has been reported to influence CDH1 transcription and thereby represents a strong candidate for a predisposition locus. To examine this proposition, we conducted a two-staged association study based on genotyping a total of 5,679 CRC cases and 5,412 controls for rs16260. CDH1-160C>A genotype was associated with CRC risk (p(trend) = 0.001). Compared to common homozygotes, the odds ratios (ORs) of CRC associated with heterozygous and homozygote variant genotype were 0.90 (95% confidence interval [CI]: 0.84-0.97) and 0.81 (95% CI: 0.71-0.93), respectively. In combination with the previously identified 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 risk variants, the risk of CRC increases with an increasing numbers of variant alleles for the 7 loci (OR(per allele) = 1.16; 95% CI: 1.13-1.19; p(trend) = 1.68 x 10(-34)). These data indicate CDH1-160C>A is a risk factor for CRC, and because a high proportion of the European population are carriers of at-risk genotypes, the variant is likely to contribute substantially to the development of CRC. Furthermore, our study underscores the importance of conducting association studies using large sample series to demonstrate polymorphic variants conferring modest relative risks.
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Affiliation(s)
- Alan M Pittman
- Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK
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Cyclin D1 A870G polymorphism in Brazilian colorectal cancer patients. J Gastrointest Cancer 2009; 39:118-23. [PMID: 19373442 DOI: 10.1007/s12029-009-9057-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2008] [Accepted: 03/18/2009] [Indexed: 01/29/2023]
Abstract
INTRODUCTION Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle. A common G to A polymorphism in the CCND1 gene is implicated on the splicing of the CCND1 transcript, and this protein may be associated to a deregulated cell proliferation. AIM Correlate the polymorphism A870G of CCND1 to the risk of colorectal cancer (CRC), to environmental risk factors and clinical aspects in Brazilian patients. PATIENTS AND METHODS One hundred twenty-three Brazilian patients with colorectal cancer were matched by age and sex to 120 healthy individuals. PCR-RFLP was performed to investigate the A870G CCND1 genotype. RESULTS Between the cases 70 were men, the mean age was 62.6 years, 74.78% were stage II or III, and 91% were well or moderately differentiated. The patients were followed for a mean time of 37.22 months. The frequency of ethanol and fat intake was similar among the groups. Patients with a family history of CRC had a higher frequency of CRC compared with the controls (OR 4.16, CI 1.89-9.16). There was no difference in the frequency of the alleles A (43.8% versus 43.9%) and G (56.3% versus 56.1%) in the groups. In analysis of both control and cancer group, the influence of sex, smoking, alcohol, fiber, or meat intake did not differ significantly according to CCND1 genotype. The genotype AA or AG was associated with an increased risk of CRC (OR 3.63 CI 1.25-10.5) in patients with a family history of cancer. We did not find any association among the genotypes and localization of the tumor or prognosis. Although a difference on age onset of the tumor and genotype was not observed, patients with GG genotype had a mean 8 years lower than the others. This genotype was also associated to an increase risk of metastatic disease (OR 3.47, CI 1.38-8.68, p = 0.024). CONCLUSION We did not find a correlation among the polymorphism of CCND1 A870G and colorectal cancer risk or between this polymorphism and lifestyle habits, diet, or follow-up. GG genotype patients had an increased risk of advanced disease and between the young patients, this genotype was associated to a lower mean age. On the other hand, the genotype AA or AG had been involved to a higher risk of CRC in patients with family history of CRC.
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Pabalan N, Bapat B, Sung L, Jarjanazi H, Francisco-Pabalan O, Ozcelik H. Cyclin D1 Pro241Pro (CCND1-G870A) polymorphism is associated with increased cancer risk in human populations: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2008; 17:2773-81. [PMID: 18843022 DOI: 10.1158/1055-9965.epi-08-0169] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The G870A polymorphism in the CCND1 gene may influence cancer risk. However, data from published studies with individual low statistical power have been controversial. To evaluate whether combined evidence shows an association between this polymorphism and cancer, we considered all available studies in a meta-analysis. Sixty studies were combined representing data for 18,411 cases and 22,209 controls. In our meta-analysis, we investigated overall sample and two ethnic populations (Caucasians and Asians) as well as nine cancer subtypes. Individuals who are homozygous for A allele (AA) were found to be associated with significantly increased cancer risk in overall sample [odds ratio (OR), 1.23; 95% confidence interval (95% CI), 1.13-1.33; P <or= 0.0001], Caucasians (OR, 1.16; 95% CI, 1.07-1.26; P=0.0002), and Asians (OR, 1.26; 95% CI, 1.14-1.39; P <or= 0.001). Among the nine cancer subtypes investigated, modestly significant risk (ORs, 1.08 to 1.51; P=0.02 to 0.04) was detected in breast, colorectal, head and neck, and other cancers. Highly significant and increased risk was found to be associated with genitourinary (OR, 1.51; 95% CI, 1.20-1.89; P=0.0004) and blood-related cancers (OR, 1.62; 95% CI, 1.28-2.05; P <or= 0.0001). Individuals who are heterozygous for AG were found to be at increased risk in overall, ethnic groups, as well as breast and colorectal cancers. Significant dominant effects seem to prevail in the majority of the categories investigated, where some recessive effects were also detected. Overall, the risk effects associated with this polymorphism were small; however, due its common occurrence, it affects a large portion of the human population (AA, 25%; AG, 50%). Although the independent small risk associated with CCND1-A870G polymorphism is not clinically useful, its interaction with other genetic variants and environmental factors has been shown to be associated with further increase in cancer risk (OR, 1.6-7.1). In conclusion, our study strongly supports the increased cancer risk associated with CCND1-A870G polymorphism in the human population.
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Affiliation(s)
- Noel Pabalan
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray Street, Room L6-304, Box 29, Toronto, Ontario, Canada M5T 3L9
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Cheah PY. Recent advances in colorectal cancer genetics and diagnostics. Crit Rev Oncol Hematol 2008; 69:45-55. [PMID: 18774731 DOI: 10.1016/j.critrevonc.2008.08.001] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2008] [Revised: 07/11/2008] [Accepted: 08/13/2008] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers and leading cause of cancer mortality worldwide. It is also one of the most curable cancers if detected early. This review classifies the diverse disease subtypes using various parameters including phenotypes of the polyps and describes how recent advances in genetics have impacted on disease diagnostics. For familial syndromes, the discovery of initiating mutations in the germline made personalized medicine a reality. A model linking the main tumorigenesis (Wnt/TGF-beta-BMP/LKB-1/PI3K-AKT) pathways and a strategy for gene testing are proposed. For sporadic CRC, high throughput technology has enabled the discovery of susceptibility loci that increased CRC risk. The ramifications of screening the population for susceptibility loci are discussed.
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Affiliation(s)
- Peh Yean Cheah
- Department of Colorectal Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Republic of Singapore.
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Jing JC, Xiong WJ, Jin H, Ji BN. Relationship between CCND1 gene A870G polymorphism and genetic susceptibility to colorectal cancer. Shijie Huaren Xiaohua Zazhi 2008; 16:2553-2556. [DOI: 10.11569/wcjd.v16.i22.2553] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the possible association between CCND1 gene A870G polymorphism and susceptibility to colorectal cancer (CRC) in Shanghai population.
METHODS: CCND1 gene A870G genotypes were determined using real-time PCR technology with TaqMan MGB probes in 104 CRC cases and 205 sex-, age-matched controls.
RESULTS: The frequencies of A and G alleles were 0.601 and 0.399 in CRC cases, and 0.524 and 0.476 in controls, respectively. The A allele was marginally associated with CRC (P = 0.057) and had an increased risk for CRC (95%CI: 0.99-1.97) as compared with the G allele. Compared with GG genotype, GA genotype had a 1.99-fold increased risk (95%CI: 0.94-4.20, P = 0.070), whereas AA genotype had a 2.46-fold increased risk (95%CI: 1.09-5.56, P = 0.031) for CRC. The A-allele carriers (GA or AA genotypes) had a significantly elevated CRC risk (OR = 2.13, 95%CI: 1.03-4.39, P = 0.040) when as compared with GG genotype.
CONCLUSION: The A allele of CCND1 A870G is associated with the occurrence of CRC, which may serve as an index for screening high-risk population in Shanghai.
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Effects of common haplotypes of the ileal sodium dependent bile acid transporter gene on the development of sporadic and familial colorectal cancer: a case control study. BMC MEDICAL GENETICS 2008; 9:70. [PMID: 18644122 PMCID: PMC2492852 DOI: 10.1186/1471-2350-9-70] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2008] [Accepted: 07/21/2008] [Indexed: 11/10/2022]
Abstract
BACKGROUND The genetics of sporadic and non-syndromic familial colorectal cancer (CRC) is not well defined. However, genetic factors that promote the development of precursor lesions, i.e. adenomas, might also predispose to CRC. Recently, an association of colorectal adenoma with two variants (c.507C>T;p.L169L and c.511G>T;p.A171S) of the ileal sodium dependent bile acid transporter gene (SLC10A2) has been reported. Here, we reconstructed haplotypes of the SLC10A2 gene locus and tested for association with non-syndromic familial and sporadic CRC compared to 'hyper-normal' controls who displayed no colorectal polyps on screening colonoscopy. METHODS We included 150 patients with sporadic CRC, 93 patients with familial CRC but exclusion of familial adenomatous polyposis and Lynch's syndrome, and 204 'hyper-normal' controls. Haplotype-tagging SLC10A2 gene variants were identified in the Hapmap database and genotyped using PCR-based 5' exonuclease assays with fluorescent dye-labelled probes. Haplotypes were reconstructed using the PHASE algorithm. Association testing was performed with both SNPs and reconstructed haplotypes. RESULTS Minor allele frequencies of all SLC10A2 polymorphisms are within previously reported ranges, and no deviations from Hardy-Weinberg equilibrium are observed. However, we found no association with any of the SLC10A2 haplotypes with sporadic or familial CRC in our samples (all P values > 0.05). CONCLUSION Common variants of the SLC10A2 gene are not associated with sporadic or familial CRC. Hence, albeit this gene might be associated with early stages of colorectal neoplasia, it appears not to represent a major risk factor for progression to CRC.
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