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Rostami M, Mahmoudi T, Ardalani A, Mashaollahi A, Zafarjafarzadeh N, Mahban A, Roshani KB, Ghasemi F, Ourang Z, Dehghanitafti A, Kaboli HS, Rezamand G, Asadi A, Dabiri R, Nobakht H, Tabaeian SP, Zali MR. The rs2275738 variant of the adiponectin receptor 1 gene is associated with biopsy-proven nonalcoholic fatty liver disease. Per Med 2024; 21:367-372. [PMID: 39469878 DOI: 10.1080/17410541.2024.2413354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 10/03/2024] [Indexed: 10/30/2024]
Abstract
Aim: Nonalcoholic fatty liver disease (NAFLD) is a significant health issue worldwide. This study investigated the effect of the adiponectin receptor 1 gene (ADIPOR1) polymorphism on susceptibility to NAFLD.Methods: Data from 330 participants, including 165 biopsy-proven NAFLD patients and 165 healthy controls, were collected. The PCR-RFLP method was used to detect the genotypes of ADIPOR1 rs2275738 or T-106C variant.Results: The "CC" genotype of the ADIPOR1 rs2275738 polymorphism, compared with the "TT" genotype and the "C" allele, compared with the "T" allele, are markers of increased NAFLD susceptibility (p = 0.018; OR = 2.07, 95% CI = 1.43-2.01 and p = 0.041; OR = 1.52, 95% CI = 1.24-2.35, respectively).Conclusion: This research suggests, for the first time, that the ADIPOR1 rs2275738 "CC" genotype is associated with a 107% increased risk for biopsy-proven NAFLD.
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Affiliation(s)
- Mitra Rostami
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Touraj Mahmoudi
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Abbas Ardalani
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Amirhesam Mashaollahi
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Nikta Zafarjafarzadeh
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Aidin Mahban
- Department of Business Management, Science & Research Branch, Islamic Azad University, Tehran, 1477893855, Iran
| | - Kosar Babaeian Roshani
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Fatemeh Ghasemi
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Zahra Ourang
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Atefeh Dehghanitafti
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Helia Sadat Kaboli
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
| | - Gholamreza Rezamand
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, 1445613131, Iran
| | - Asadollah Asadi
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, 5619911367, Iran
| | - Reza Dabiri
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, 3513138111, Iran
| | - Hossein Nobakht
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, 3513138111, Iran
| | - Seidamir Pasha Tabaeian
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, 1445613131, Iran
| | - Mohammad Reza Zali
- Gastroenterology & Liver Diseases Research Center, Research Institute for Gastroenterology & Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
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Asadi A, Rostami M, Shafiee R, Ardalani A, Dehghanitafti A, Golshadi Z, Kohansal K, Ghasemi F, Najafi M, Mahmoudi T, Rezamand G, Dabiri R, Nobakht H, Farahani H, Tabaeian SP. Association of IRS1 gene Pro512Ala polymorphism with nonalcoholic fatty liver disease. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2024; 68:e230216. [PMID: 39420901 PMCID: PMC11460970 DOI: 10.20945/2359-4292-2023-0216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 10/02/2023] [Indexed: 10/19/2024]
Abstract
Objective This study was designed to investigate the possible effect of the insulin receptor substrate 1 (IRS1) gene rs1801276 polymorphism on the risk of nonalcoholic fatty liver disease (NAFLD). Subjects and methods The rs1801276 polymorphism was investigated in 127 controls and 123 biopsy-proven NAFLD patients using PCR-RFLP. Results No deviation from Hardy-Weinberg equilibrium was discovered for the rs1801276 variant of IRS1 in either NAFLD patients or controls (P>0.05). The distribution of different rs1801276 genotypes and alleles showed significant variations between controls and NAFLD patients. In comparison to rs1801276 'CC' genotype, the "GG+GC" genotype occurred less frequently in NAFLD patients than in controls, which also persisted after adjustment for confounding factors (P = 0.041, OR = 0.60, 95% CI = 0.45-0.93). In comparison with the IRS1 rs1801276 "C" allele, the "G" allele was significantly less prevalent in NAFLD patients than in controls (P = 0.045, OR = 0.69, 95% CI = 0.58-0.91). Conclusions For the first time, we reported a significant association between the IRS1 rs1801276 polymorphism and biopsy-proven NAFLD. More studies are required to further elucidate the contribution of the IRS1 gene to NAFLD susceptibility.
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Affiliation(s)
- Asadollah Asadi
- University of Mohaghegh ArdabiliFaculty of ScienceDepartment of BiologyArdabilIranDepartment of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Mitra Rostami
- Shahid Beheshti University of Medical SciencesResearch Institute for Gastroenterology and Liver DiseasesGastroenterology and Liver Diseases Research CenterTehranIranGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Radmehr Shafiee
- Tehran UniversityFaculty of Veterinary MedicineDepartment of Clinical PathologyIranDepartment of Clinical Pathology, Faculty of Veterinary Medicine, Tehran University, Iran
| | - Abbas Ardalani
- Shahid Beheshti University of Medical SciencesResearch Institute for Gastroenterology and Liver DiseasesGastroenterology and Liver Diseases Research CenterTehranIranGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Dehghanitafti
- Shahid Beheshti University of Medical SciencesResearch Institute for Gastroenterology and Liver DiseasesGastroenterology and Liver Diseases Research CenterTehranIranGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zakieh Golshadi
- Shahid Beheshti University of Medical SciencesResearch Institute for Gastroenterology and Liver DiseasesGastroenterology and Liver Diseases Research CenterTehranIranGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kiarash Kohansal
- Iran University of Medical SciencesPhysiology Research CenterTehranIranPhysiology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ghasemi
- Shahid Beheshti University of Medical SciencesResearch Institute for Gastroenterology and Liver DiseasesGastroenterology and Liver Diseases Research CenterTehranIranGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Najafi
- Shahid Beheshti University of Medical SciencesResearch Institute for Gastroenterology and Liver DiseasesGastroenterology and Liver Diseases Research CenterTehranIranGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Touraj Mahmoudi
- Shahid Beheshti University of Medical SciencesResearch Institute for Gastroenterology and Liver DiseasesGastroenterology and Liver Diseases Research CenterTehranIranGastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gholamreza Rezamand
- Iran University of Medical SciencesSchool of MedicineDepartment of Internal MedicineTehranIranDepartment of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Iran University of Medical SciencesColorectal Research CenterTehranIranColorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Dabiri
- Semnan University of Medical SciencesInternal Medicine DepartmentSemnanIranInternal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Hossein Nobakht
- Semnan University of Medical SciencesInternal Medicine DepartmentSemnanIranInternal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Hamid Farahani
- Qom University of Medical SciencesSchool of MedicineDepartment of Physiology and PharmacologyQomIranDepartment of Physiology and Pharmacology, School of Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Seidamir Pasha Tabaeian
- Iran University of Medical SciencesSchool of MedicineDepartment of Internal MedicineTehranIranDepartment of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Iran University of Medical SciencesColorectal Research CenterTehranIranColorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
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Nguyen LTD, Gunathilake M, Lee J, Oh JH, Chang HJ, Sohn DK, Shin A, Kim J. The interaction between magnesium intake, the genetic variant INSR rs1799817 and colorectal cancer risk in a Korean population: a case-control study. Int J Food Sci Nutr 2024; 75:396-406. [PMID: 38389245 DOI: 10.1080/09637486.2024.2314678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 01/30/2024] [Indexed: 02/24/2024]
Abstract
Magnesium may have a significant impact on the development of cancer. However, the relationship between magnesium intake and the risk of colorectal cancer (CRC) is unclear. Therefore, we evaluated the association between magnesium intake and the risk of CRC, and we investigated how the insulin receptor (INSR) rs1799817 variant impacts this relationship. Data from 1,420 CRC patients and 2,840 controls from the Korean National Cancer Centre were analysed. A higher intake of magnesium was associated with a reduced risk of CRC in the total population (odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52-0.81). We found that G + carriers of INSR rs1799817 with higher magnesium intake had a significantly lower risk of CRC (p for interaction = 0.003). Our findings indicated that high magnesium intake could be associated with a decreased risk of CRC, and this association could be modified by the INSR rs1799817 variant.
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Affiliation(s)
- Linh Thi Dieu Nguyen
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Madhawa Gunathilake
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Jeonghee Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Hee Jin Chang
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Dae Kyung Sohn
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
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Nouri S, Mahmoudi T, Hojjati F, Najafabadi ZN, Shafiee R, Sayedsalehi S, Dehghanitafti A, Ardalani A, Kohansal K, Rezamand G, Asadi A, Nobakht H, Dabiri R, Farahani H, Tabaeian SP, Zali MR. Insulin receptor substrate 2 gene Gly1057Asp polymorphism is a risk factor for nonalcoholic fatty liver disease. Lab Med 2024; 55:215-219. [PMID: 37481466 DOI: 10.1093/labmed/lmad066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2023] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD), which is an emerging global chronic liver disease, has a close association with insulin resistance. We aimed to determine whether the Gly1057Asp (rs1805097) polymorphism of the insulin receptor substrate 2 (IRS2) gene is associated with NAFLD. METHODS Using the polymerase chain reaction-restriction fragment length polymorphism method, 135 patients with biopsy-proven NAFLD and 135 controls underwent IRS2 genotype analysis. RESULTS Genotype and allele distributions of the IRS2 gene Gly1057Asp variant conformed to the Hardy-Weinberg equilibrium in both the case and control groups (P > .05). The Asp/Asp genotype of IRS2 gene Gly1057Asp polymorphism compared with Gly/Gly genotype was associated with a 2.1-fold increased risk for NAFLD after adjustment for confounding factors (P = .029; odds ratio = 2.10, 95% CI = 1.23-3.97). CONCLUSION Our findings revealed for the first time that the Gly1057Asp Asp/Asp genotype of the IRS2 gene is a marker of increased NAFLD susceptibility; however, studies in other populations are required to confirm the results.
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Affiliation(s)
- Shadi Nouri
- Department of Radiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Touraj Mahmoudi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzaneh Hojjati
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Radmehr Shafiee
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Tehran University, Tehran, Iran
| | - Shiva Sayedsalehi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atefeh Dehghanitafti
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Ardalani
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kiarash Kohansal
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Gholamreza Rezamand
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Asadollah Asadi
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Hossein Nobakht
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Reza Dabiri
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Hamid Farahani
- Department of Physiology and Pharmacology, School of Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Seidamir Pasha Tabaeian
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Govahi Kakhki F, Sargazi S, Montazerifar F, Majidpour M, Karajibani A, Karajibani M, Ghasemi M. IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome. J Clin Lab Anal 2024; 38:e25021. [PMID: 38468402 PMCID: PMC10959184 DOI: 10.1002/jcla.25021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 01/20/2024] [Accepted: 02/15/2024] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND Insulin resistance has been correlated with the genetic diversity within the insulin-like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk. METHODS A total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case-control cross-sectional study. Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS The CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34-0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease. CONCLUSIONS IGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.
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Affiliation(s)
- Fatemeh Govahi Kakhki
- Department of Nutrition, School of MedicineZahedan University of Medical SciencesZahedanIran
| | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious DiseasesZahedan University of Medical SciencesZahedanIran
- Department of Clinical Biochemistry, School of MedicineZahedan University of Medical SciencesZahedanIran
| | - Farzaneh Montazerifar
- Department of Nutrition, School of MedicineZahedan University of Medical SciencesZahedanIran
- Pregnancy Health Research CenterZahedan University of Medical SciencesZahedanIran
| | - Mahdi Majidpour
- Clinical Immunology Research Center, Zahedan University of Medical SciencesZahedanIran
| | - Atena Karajibani
- Department of BiologyUniversity of Sistan and BaluchestanZahedanIran
| | - Mansour Karajibani
- Department of Nutrition, School of MedicineZahedan University of Medical SciencesZahedanIran
- Health Promotion Research CenterZahedan University of Medical SciencesZahedanIran
| | - Marzieh Ghasemi
- Pregnancy Health Research CenterZahedan University of Medical SciencesZahedanIran
- Moloud Infertility Center, Ali Ibn Abitaleb HospitalZahedan University of Medical SciencesZahedanIran
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Cheraghpour M, Askari M, Tierling S, Shojaee S, Sadeghi A, Ketabi Moghadam P, Khazdouz M, Asadzadeh Aghdaei H, Piroozkhah M, Nazemalhosseini-Mojarad E, Fatemi N. A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility. Front Oncol 2023; 13:1168942. [PMID: 37284192 PMCID: PMC10240407 DOI: 10.3389/fonc.2023.1168942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 05/04/2023] [Indexed: 06/08/2023] Open
Abstract
BACKGROUND The receptors, ligands, and associated proteins of the insulin-like growth factor (IGF) family are involved in cancer development. The IGF1 receptor and its accompanying signaling cascade are a crucial growth-regulatory mechanism that plays an important role in colorectal cancer (CRC) proliferation and differentiation. IRS1 (Insulin receptor substrate-1), a major substrate for the IGF1R, is involved in cell growth and promotes tumorigenesis. There are shreds of evidence from prior research suggesting that IGF system polymorphisms may influence susceptibility to CRC. However, the findings in this area were contradictory. Accordingly, we carried out a systematic literature search to identify all case-control, cross-sectional, and cohort studies on the association between various polymorphisms across four IGF1 pathway genes (IGF1, IGF1R, IRS1, and IRS2) and the risk of CRC. METHODS We performed a comprehensive search strategy in PubMed, Scopus, and Web of Science databases for articles available until Aug 30, 2022. A total of 26 eligible studies with IGF1/IGF1R, IRS1 and IRS2 polymorphisms; met the inclusion criteria. All case-control studies for IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A comprising 22,084 cases and 29,212 controls were included in the current meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the polymorphisms and CRC susceptibility. All statistical analyses were performed using STATA software version 14.0. RESULTS The meta-analysis of available data for rs6214C>T, rs1801278G>A, and rs1805097G>A showed a significant association between these polymorphisms and an increased CRC risk in some of the comparisons studied (rs6214C>T, pooled OR for CC = 0.43, 95% CI 0.21- 0.87, P = 0.019; rs1801278G>A, OR for GA = 0.74, 95% CI 0.58-0.94, P = 0.016; rs1805097G>A, OR for GA = 0.83, 95% CI 0.71-0.96, P = 0.013). Nevertheless, the meta-analysis did not include other genetic variations in IGF1, IGF1R, IRS1, and IRS2 due to heterogeneity and limited sample size. CONCLUSIONS This systematic review and meta-analysis provide evidence that genetic variants in IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A are associated with an increased risk of CRC. These findings may contribute to a better understanding of the complex genetic mechanisms involved in CRC development and could inform future research on prevention and treatment strategies for this disease.
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Affiliation(s)
- Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masomeh Askari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sascha Tierling
- Department of Genetics/Epigenetics, Faculty NT, Saarland University, Saarbrücken, Germany
| | - Sajad Shojaee
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pardis Ketabi Moghadam
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Khazdouz
- Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Moein Piroozkhah
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nayeralsadat Fatemi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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7
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Tabaeian SP, Mahmoudi T, Rezamand G, Nobakht H, Dabiri R, Farahani H, Asadi A, Zali MR. RESISTIN GENE POLYMORPHISM AND NONALCOHOLIC FATTY LIVER DISEASE RISK. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:483-487. [PMID: 36515343 DOI: 10.1590/s0004-2803.202204000-86] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 06/01/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and one of the main global health issues in which liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Owing to the link between NAFLD and insulin resistance (IR) and obesity and the role of resistin in theses metabolic disorders, we explored the possible association between resistin gene (RETN) variant and NAFLD. METHODS A total of 308 unrelated subjects, including 152 patients with biopsy-proven NAFLD and 156 controls were enrolled and genotyped for the RETN gene rs3745367 variant using PCR-RFLP method. RESULTS NAFLD patients had higher liver enzymes, systolic blood pressure (SBP), and diastolic blood pressure (DBP) than the controls (P<0.001). However, we observed no significant difference in genotype and allele frequencies between the cases with NAFLD and the controls for the RETN rs3745367 polymorphism either before or after adjustment for confounding factors including age, BMI, sex, smoking status, SBP, and DBP. CONCLUSION To our knowledge, this study is the first one that investigated the association between RETN gene rs3745367 variant and biopsy-proven NAFLD. Our findings do not support a role for this gene polymorphism in NAFLD risk in Iranian population; nonetheless, they need to be further investigated in other populations.
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Affiliation(s)
- Seidamir Pasha Tabaeian
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Touraj Mahmoudi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gholamreza Rezamand
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Nobakht
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Reza Dabiri
- Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran
| | - Hamid Farahani
- Department of Physiology and Pharmacology, School of Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Asadollah Asadi
- Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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8
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OUP accepted manuscript. Lab Med 2022; 53:504-508. [DOI: 10.1093/labmed/lmac039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Rasool SUA, Ashraf S, Nabi M, Masoodi SR, Fazili KM, Amin S. Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS. Int J Endocrinol 2021; 2021:7522487. [PMID: 34912452 PMCID: PMC8668320 DOI: 10.1155/2021/7522487] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 11/15/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder affecting premenopausal women. Besides primary features like anovulation, hyperandrogenism, and polycystic ovaries, women with PCOS present with multiple metabolic, cardiovascular, and psychological disorders. The etiology is multifactorial and the different genetic variants are suggested to play an important role in pathogenesis. Insulin resistance is a ubiquitous finding in PCOS and SNPs in genes involved in the insulin signaling pathway are possible candidates that can explain the development of clinical manifestations of PCOS. AIM We aimed to investigate the association of INSR His1058 C/T (rs1799817) single nucleotide polymorphism with PCOS in Kashmiri women. The genotypic-phenotypic correlation of the tested SNP with hyperandrogenism, ovulatory dysfunction, and metabolic markers was evaluated. RESULTS The allele frequency (OR = 1.00, 95% CI = 0.67-1.48, χ 2 = 0.01, P=0.99) and genotype distribution (χ 2 = 3.73, P=0.15) in INSR C/T polymorphism were comparable with controls. No significant association was found with PCOS in dominant (P=0.194), recessive (P=0.442), and homo vs. het. (P=0.5) genotype models. Genotype-phenotype correlation analysis revealed that variant TT genotype had significantly higher HOMA (P=0.029) and reduced insulin sensitivity QUICKI (P=0.037) values. There was no significant variation in the prevalence of hirsutism, acne, alopecia, menstrual disturbances, acanthosis nigricans, and obesity (all P > 0.05) in different INSR C/T genotypes. CONCLUSION The INSR C/T SNP (rs1799817) does not increase the risk of PCOS in Kashmiri women. This SNP is unlikely to play a significant role in the development and manifestation of clinical symptoms of polycystic ovary syndrome.
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Affiliation(s)
| | - Sairish Ashraf
- Department of Biochemistry, University of Kashmir, Srinagar, India
| | - Mudasar Nabi
- Department of Biochemistry, University of Kashmir, Srinagar, India
| | - Shariq R. Masoodi
- Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India
| | - Khalid M. Fazili
- Department of Biotechnology, University of Kashmir, Srinagar, India
| | - Shajrul Amin
- Department of Biochemistry, University of Kashmir, Srinagar, India
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Jung SY, Zhang ZF. The effects of genetic variants related to insulin metabolism pathways and the interactions with lifestyles on colorectal cancer risk. Menopause 2019; 26:771-780. [PMID: 30649085 PMCID: PMC7035960 DOI: 10.1097/gme.0000000000001301] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Genetic variants in metabolic signaling pathways may interact with lifestyle factors, such as dietary fatty acids, influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated pathways are not fully understood. METHODS In this study, we examined 54 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I/insulin traits and their signaling pathways and lifestyle factors in relation to postmenopausal CRC, using data from 6,539 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies. By employing a two-stage random survival forest analysis, we evaluated the SNPs and lifestyle factors by ranking them according to their predictive value and accuracy for CRC. RESULTS We identified four SNPs (IRS1 rs1801123, IRS1 rs1801278, AKT2 rs3730256, and AKT2 rs7247515) and two lifestyle factors (age and percentage calories from saturated fatty acids) as the top six most influential predictors for CRC risk. We further examined interactive effects of those factors on cancer risk. In the individual SNP analysis, no significant association was observed, but the combination of the four SNPs, age, and percentage calories from saturated fatty acid (≥11% per day) significantly increased the risk of CRC in a gene and lifestyle dose-dependent manner. CONCLUSIONS Our findings provide insight into gene-lifestyle interactions and will enable researchers to focus on individuals with risk genotypes to promote intervention strategies. Our study suggests the careful use of data on potential genetic targets in clinical trials for cancer prevention to reduce the risk for CRC in postmenopausal women.
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Affiliation(s)
- Su Yon Jung
- Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, Los Angeles, CA, USA
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA
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Tang W, Liu J, Zhong Z, Qiu H, Kang M. Association of metabolism-related genes polymorphisms with adenocarcinoma of the oesophagogastric junction: Evidence from 2261 subjects. J Cell Biochem 2019; 120:18689-18701. [PMID: 31211453 PMCID: PMC6771939 DOI: 10.1002/jcb.29167] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 05/17/2019] [Accepted: 05/23/2019] [Indexed: 01/26/2023]
Abstract
The etiology of adenocarcinoma of the esophagogastric junction (AEG) remains unclear. It is believed that the increasing of AEG may be correlated with the elevated ratio of obesity and overweight. Thus, metabolism‐related genes and variants may play important roles in the occurrence and progress of AEG. The current investigation involved 720 patients with AEG and 1541 healthy controls. We selected transcription factor 7‐like 2 (TCF7L2) rs7903146 and rs290481, INS rs689 and INSR rs1799817 single‐nucleotide polymorphisms (SNPs), and explored the association of these SNPs with lymph node status and risk of AEG. The polymerase chain reaction was harnessed to identify the genotyping of four polymorphisms. We found that TCF7L2 rs290481 (T > C) and INSR rs1799817 (G > A) polymorphisms were associated with the increased susceptibility of AEG (P = .007 and 0.004 for TCF7L2 rs290481 in TC vs TT and TC/CC vs TT models, and P = .040 for INSR rs1799817 in GA/AA vs GG model). We also conducted a subgroup analysis by different cancer stage. We identified that TCF7L2 rs290481, INS rs689, and INSR rs1799817 SNPs increased the susceptibility of AEG in different cancer stage subgroups. In addition, we found that rs290481 SNP in TCF7L2 gene increased the risk of lymph node metastasis in drinking patients with AEG. However, the association of INSR rs1799817 SNP with a decreased risk of lymph node metastasis in smoking patients with AEG was found. Our findings highlight that TCF7L2 rs290481, INS rs689, and INSR rs1799817 polymorphisms may increase the risk of AEG. In addition, TCF7L2 rs290481 and INSR rs1799817 SNPs may influence the lymph node metastasis in patients with AEG.
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Affiliation(s)
- Weifeng Tang
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Jun Liu
- Department of Medical Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Zhihui Zhong
- Department of Orthopaedics, The Fuzhou Second Hospital, Affiliated Hospital of Xiamen University, Fuzhou, Fujian, China
| | - Hao Qiu
- Department of Immunology, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Mingqiang Kang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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Tang W, Chen S, Liu J, Liu C, Wang Y, Kang M. Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk. J Cell Biochem 2018; 120:5510-5518. [PMID: 30335898 PMCID: PMC6587846 DOI: 10.1002/jcb.27834] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 09/14/2018] [Indexed: 12/12/2022]
Abstract
Esophagogastric junction adenocarcinoma (EGJA) may be associated with obesity and overweight. Thus, any variant in energy metabolism–related gene may influence the development of EGJA. In this study, we recruited 720 EGJA cases and 1541 noncancer controls. We selected IGF2BP2 rs4402960 G > T, rs1470579 A > C,
IGF1 rs5742612 A > G and
IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci and assessed the relationship of these polymorphisms with lymph node status and susceptibility of EGJA. We found that
IGF2BP2 rs1470579 A > C and
IGFBP3 rs6953668 G > A polymorphisms were associated with the decreased risk of EGJA (
IGF2BP2 rs1470579: CC vs AA: adjusted odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43‐0.98,
P = 0.041 and CC vs AA/AC: adjusted OR = 0.62, 95% CI = 0.41‐0.93,
P = 0.021 and
IGFBP3 rs6953668: GA vs GG: adjusted OR = 0.66, 95% CI = 0.47‐0.93,
P = 0.019 and GA/AA vs GG: adjusted OR = 0.68, 95% CI = 0.48‐0.95,
P = 0.026). However, we also found that
IGF1 rs5742612 A > G polymorphism increased the risk of LNM among patients with EGJA (GG vs AA: adjusted OR = 1.88, 95% CI = 1.02‐3.46,
P = 0.042 and GG vs AA/AG: adjusted OR = 1.92, 95% CI = 1.06‐3.47,
P = 0.032). This study suggests that
IGF2BP2 rs1470579 A > C and
IGFBP3 rs6953668 G > A polymorphisms may decrease genetic susceptibility to EGJA in eastern Chinese Han population. In addition, our findings also indicate that
IGF1 rs5742612 A > G polymorphism may increase the susceptibility of LNM among patients with EGJA.
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Affiliation(s)
- Weifeng Tang
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Shuchen Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China.,Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian, China
| | - Jun Liu
- Central Lab, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Chao Liu
- Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yafeng Wang
- Department of Cardiology, The People's Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong, Yunnan, China
| | - Mingqiang Kang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China.,Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian, China
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Yin J, Zhang Z, Zheng H, Xu L. IRS-2 rs1805097 polymorphism is associated with the decreased risk of colorectal cancer. Oncotarget 2018; 8:25107-25114. [PMID: 28212577 PMCID: PMC5421913 DOI: 10.18632/oncotarget.15342] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 01/27/2017] [Indexed: 01/11/2023] Open
Abstract
Recent studies explored the association between insulin receptor substrate-2 (IRS-2) gene rs1805097 polymorphism and colorectal cancer (CRC) with contradictory findings. Therefore, we conducted a comprehensive meta-analysis by searching the databases of PubMed and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 5 citations containing 6 case-control studies involving 4,333 cases and 5,333 controls were included. Our data indicated that IRS-2 rs1805097 polymorphism was associated with decreased risk of CRC. Stratification analysis of ethnicity found that rs1805097 polymorphism decreased the risk of CRC among Americans. Stratification analysis of cancer type suggested that this polymorphism decreased the risk of colon cancer. In summary, this meta-analysis indicates that IRS-2 gene rs1805097 polymorphism plays an important role in the pathogenesis of CRC.
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Affiliation(s)
- Jiefeng Yin
- General Surgery Department, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Zhe Zhang
- General Surgery Department, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Huajun Zheng
- Department of Digestion, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Lei Xu
- Department of Digestion, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Jung SY, Rohan T, Strickler H, Bea J, Zhang ZF, Ho G, Crandall C. Genetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk. PLoS One 2017; 12:e0186296. [PMID: 29023587 PMCID: PMC5638514 DOI: 10.1371/journal.pone.0186296] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 09/28/2017] [Indexed: 02/08/2023] Open
Abstract
Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/ insulin resistance (IR) traits and signaling pathways, using data from 704 postmenopausal women in Women’s Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment–insulin resistance) on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway–related genetic variants) had different associations with CRC risk between strata, and the proportion of the SNP–cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene–phenotype–lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.
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Affiliation(s)
- Su Yon Jung
- Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, Los Angeles, California, United States of America
- * E-mail:
| | - Thomas Rohan
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America
| | - Howard Strickler
- Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America
| | - Jennifer Bea
- Medicine & Nutritional Sciences, University of Arizona Cancer Center, Tucson, Arizona, United States of America
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, United States of America
| | - Gloria Ho
- Department of Occupational Medicine, Epidemiology and Prevention, Feinstein Institute for Medical Research, Hofstra Northwell School of Medicine, Great Neck, New York, United States of America
| | - Carolyn Crandall
- Division of General Internal Medicine, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America
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A Common Promoter Polymorphism (-23HphI) in Insulin Gene and Susceptibility to Colorectal Cancer. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2017. [DOI: 10.5812/ijcm.10079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Petkevicius V, Salteniene V, Juzenas S, Wex T, Link A, Leja M, Steponaitiene R, Skieceviciene J, Kupcinskas L, Jonaitis L, Kiudelis G, Malfertheiner P, Kupcinskas J. Polymorphisms of microRNA target genes IL12B, INSR, CCND1 and IL10 in gastric cancer. World J Gastroenterol 2017; 23:3480-3487. [PMID: 28596683 PMCID: PMC5442083 DOI: 10.3748/wjg.v23.i19.3480] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 02/23/2017] [Accepted: 03/21/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate associations between miRNA target genes IL12B, INSR, CCND1 and IL10 polymorphisms and gastric cancer (GC) in European population. METHODS Gene polymorphisms were analyzed in 508 controls and 474 GC patients from 3 tertiary centers in Germany, Lithuania and Latvia. Controls were patients from the out-patient departments, who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy. Gastric cancer (GC) patients had histopathological verification of gastric adenocarcinoma. Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells. IL12B T>G (rs1368439), INSR T>C (rs1051690), CCND1 A>C (rs7177) and IL10 T>C (rs3024498) SNPs were genotyped by the real-time polymerase chain reaction. Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex, age and country of birth. RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690. The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls (23.26% and 19.19% respectively, P = 0.028). CT genotype was also more prevalent in patients compared to control group (38.48% and 30.12% respectively, P < 0.021). Logistic regression analysis revealed that only one polymorphism (rs1051690 in INSR gene) was associated with increased risk of GC. Carriers of CT genotype had higher odds of GC when compared to CC genotype (OR = 1.45, 95%PI: 1.08-1.95, P = 0.01). Similar association was observed in a dominant model for INSR gene, where comparison of TT+CT vs CC genotypes showed an increased risk of GC (OR = 1.44, 95%PI: 1.08-1.90, P = 0.01). Other analyzed SNPs were not associated with the presence of GC. CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC, while polymorphisms in IL12B, CCND1 and IL10 genes are not linked with the presence of GC.
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