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Tahmasebi Fard Z. Evaluation of the Effect of Menopausal Status and BMI on Polymorphisms in Fas/Fas L and the Risk of Breast Cancer. Clin Breast Cancer 2025; 25:e56-e62. [PMID: 39214844 DOI: 10.1016/j.clbc.2024.07.006] [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: 10/13/2023] [Revised: 07/03/2024] [Accepted: 07/12/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND FAS and FAS ligand play an essential role in cell apoptosis. An identifying feature of malignant cells is the loss of FAS and increased FASL expression. A study analyzing the effects of menopausal status and body mass index (BMI) on functional polymorphisms of FAS-(1377G/A; rs2234767 & 670 A/G; rs1800682) and FASL (-844T/C; rs763110 & Ivs-2nt; rs5030772) in breast cancer evaluated these effects. PATIENTS AND METHODS 316 blood samples were collected from breast cancer patients and healthy controls in this case/control study. RFLP-PCR was used after DNA extraction to determine genotypes. Age, BMI, menopausal status, smoking, and family history were also analyzed with genotypes. It was analyzed using SPSS software, X2 statistical tests, logistic regression, and Pearson's correlation. The study evaluated the role of indices and polymorphisms in breast cancer risk. RESULTS While BMI and family history were significantly different, age, menopause status, and smoking were not. Examining the average BMI between menopausal and nonmenopausal people in the 2 groups showed a statistically significant difference between menopausal people (P <0.0001). As a result of 1377AA, 670GG, 844TT, and IVS-2ntGG, the risk of breast cancer increased by 1.83 times, 2.35 times, and 2.38 times respectively. In addition, mutant alleles increased disease risk significantly. The risk of disease increased considerably for postmenopausal females with certain genotypes (except 1377GA and 844CT genotypes) and high BMI. CONCLUSION Having a high BMI during postmenopause increases your risk of breast cancer. In addition to menopause, BMI also influences disease progression. Different genotypes are needed to clarify this issue.
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Affiliation(s)
- Zahra Tahmasebi Fard
- Department of Biology, Roudehen Branch, Islamic Azad University, Roudehen, Iran.
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Huang P, Wang CH, Zhuo LY, Xia XS, Yang S, Zhang JW, Fan HZ, Wu JJ, Yu R, Yue M, Zhang Y. Polymorphisms rs763110 in FASL is linked to hepatitis C virus infection among high-risk populations. Br J Biomed Sci 2020; 77:112-117. [PMID: 32209020 DOI: 10.1080/09674845.2020.1747182] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The Fas cell surface death receptor (FAS) and Fas ligand (FASL) can participate in the apoptosis of immune cells and target cells infected with a virus through the FAS-FASL signalling pathway. The decoy receptor 3 (DCR3) can competitively inhibit the binding of FAS to FASL. Our aim is to investigate the effect of single nucleotide polymorphisms (SNPs) in FAS, FASL and DCR3 on hepatitis C virus (HCV) infection. METHODS Four SNPs (rs763110 in FASL, rs1324551 and rs2234767 in FAS and rs2257440 in DCR3) were genotyped in 1495 controls free of HCV, 522 individuals with spontaneous HCV clearance and 732 patients with hepatitis C virus infection. The RegulomeDB database and RNAfold web servers were used to explore potential biological functions of SNPs. RESULTS FASL rs763110 was associated with susceptibility to HCV infection, and not to CHC. The odds ratio (95% confidence interval) of HCV infection in high-risk populations carrying FASL rs763110-TT was 1.82 (1.36-2.51, P < 0.001) compared to that of CC genotypes and 1.93 (1.43-2.60, P < 0.001) higher than that of CC + CT genotypes. Based on computer simulation, FASL rs763110-T may affect the transcription of mRNA by affecting the binding of a transcription factor, leading to structural changes in mRNA. CONCLUSION The genetic variant in FASL is linked with HCV infection, but not to spontaneous HCV clearance.
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Affiliation(s)
- P Huang
- Department of Epidemiology and Biostatistics, Key Laboratory of Infectious Diseases, Nanjing Medical University , Nanjing, China.,Institute of Epidemiology and Microbiology, Eastern Theater Command Centers for Disease Control and Prevention , Nanjing, China
| | - C H Wang
- Institute of Epidemiology and Microbiology, Eastern Theater Command Centers for Disease Control and Prevention , Nanjing, China
| | - L Y Zhuo
- Department of Epidemiology and Biostatistics, Key Laboratory of Infectious Diseases, Nanjing Medical University , Nanjing, China
| | - X S Xia
- College of Life Science and Technology, Kunming University of Science and Technology , Kunming, China
| | - S Yang
- Department of Biostatistics, School of Public Health, Nanjing Medical University , Nanjing, China
| | - J W Zhang
- Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University , Jiangsu, China
| | - H Z Fan
- Department of Information, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China
| | - J J Wu
- Department of Epidemiology and Biostatistics, Key Laboratory of Infectious Diseases, Nanjing Medical University , Nanjing, China
| | - R Yu
- Department of Epidemiology and Biostatistics, Key Laboratory of Infectious Diseases, Nanjing Medical University , Nanjing, China
| | - M Yue
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China.,State Key Laboratory of Virology, School of Basic Medical Sciences, Wuhan University , Wuhan, China
| | - Y Zhang
- Department of Epidemiology and Biostatistics, Key Laboratory of Infectious Diseases, Nanjing Medical University , Nanjing, China.,Institute of Epidemiology and Microbiology, Eastern Theater Command Centers for Disease Control and Prevention , Nanjing, China
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Netz U, Carter JV, Eichenberger MR, Dryden GW, Pan J, Rai SN, Galandiuk S. Genetic polymorphisms predict response to anti-tumor necrosis factor treatment in Crohn’s disease. World J Gastroenterol 2017; 23:4958-4967. [PMID: 28785150 PMCID: PMC5526766 DOI: 10.3748/wjg.v23.i27.4958] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 04/05/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate genetic factors that might help define which Crohn’s disease (CD) patients are likely to benefit from anti-tumor necrosis factor (TNF) therapy.
METHODS This was a prospective cohort study. Patients were recruited from a university digestive disease practice database. We included CD patients who received anti-TNF therapy, had available medical records (with information on treatment duration and efficacy) and who consented to participation. Patients with allergic reactions were excluded. Patients were grouped as ever-responders or non-responders. Genomic DNA was extracted from peripheral blood, and 7 single nucleotide polymorphisms (SNPs) were assessed. The main outcome measure (following exposure to the drug) was response to therapy. The patient genotypes were assessed as the predictors of outcome. Possible confounders and effect modifiers included age, gender, race, and socioeconomic status disease, as well as disease characteristics (such as Montreal criteria).
RESULTS 121 patients were included. Twenty-one were non-responders, and 100 were ever-responders. Fas ligand SNP (rs763110) genotype frequencies, TNF gene -308 SNP (rs1800629) genotype frequencies, and their combination, were significantly different between groups on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype (P = 0.009, OR = 4.30, 95%CI: 1.45-12.80). The presence of the A (minor) TNF gene -308 allele correlated with three-fold higher odds of being a non-responder (P = 0.049, OR = 2.88, 95%CI: 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF -308 A allele had nearly five-fold higher odds of being a non-responder (P = 0.015, OR = 4.76, 95%CI: 1.35-16.77). No difference was seen for the remaining SNPs.
CONCLUSION The Fas-ligand SNP and TNF gene -308 SNP are associated with anti-TNF treatment response in CD and may help select patients likely to benefit from therapy.
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Khankari NK, Bradshaw PT, Steck SE, He K, Olshan AF, Ahn J, Terry MB, Crew KD, Teitelbaum SL, Neugut AI, Santella RM, Gammon MD. Interaction between polyunsaturated fatty acids and genetic variants in relation to breast cancer incidence. JOURNAL OF CANCER EPIDEMIOLOGY AND PREVENTION (IMEDPUB) 2016; 1:2. [PMID: 28971183 PMCID: PMC5621474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Higher intake of ω-3 relative to ω-6 polyunsaturated fatty acids (PUFAs) may reduce breast carcinogenesis via different metabolic pathways. The PUFA-breast cancer association remains inconclusive, thus, we hypothesized that interactions between the ratio of dietary ω-3:ω-6 intake and polymorphisms from PUFA-related metabolic pathways would help elucidate an association. Utilizing resources from the Long Island Breast Cancer Study Project, a population-based case-control study (n=1035 cases/1075 controls), we examined interactions between ω-3:ω-6 ratio and 18 polymorphisms of 15 genes. Compared to the putative lowest risk group (high ω-3:ω-6,low-risk FASL rs763110 CT/TT genotype), the odds ratio (OR) for breast cancer from unconditional logistic regression models was weakly increased for other exposure-genotype combinations (high ω-3:ω-6,high-risk FASL CC genotype, OR=1.18,95% confidence interval(CI)=0.90,1.53; low ω-3:ω-6,CT/TT genotype, OR=1.35,95%CI=1.09,1.66); but was approximately null for the putative highest risk group (low ω-3:ω-6,CC genotype; OR=1.06,95%CI=0.81,1.38). We observed an interaction between the ω-3:ω-6 ratio and FASL rs763110 on the additive scale [Relative Excess Risk Due to Interaction(RERI)=-0.47, 95%CI=-0.92,-0.02]. Interactions with other polymorphisms considered were not evident. Our findings suggest that the PUFA-breast cancer association may be modified by FASL. However, additional research is needed given this interaction may be due to chance and is inconsistent with our a priori biologic hypothesis.
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Affiliation(s)
- Nikhil K Khankari
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Patrick T Bradshaw
- Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, 94720, USA
| | - Susan E Steck
- Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, 29208, USA
| | - Ka He
- Department of Epidemiology and Biostatistics, Indiana University, Bloomington, IN 47405, USA
| | - Andrew F Olshan
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Jiyoung Ahn
- Department of Population Health, New York University, New York, NY 10016, USA
- Department of Environmental Medicine, New York University, New York, NY 10016, USA
| | - Mary Beth Terry
- Department of Epidemiology, Columbia University, New York, NY, 10032, USA
| | - Katherine D Crew
- Department of Epidemiology, Columbia University, New York, NY, 10032, USA
- Department of Medicine, Columbia University, New York, NY, 10032, USA
| | - Susan L Teitelbaum
- Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA
| | - Alfred I Neugut
- Department of Epidemiology, Columbia University, New York, NY, 10032, USA
- Department of Medicine, Columbia University, New York, NY, 10032, USA
| | - Regina M Santella
- Department of Environmental Health, Columbia University, New York, NY, 10032, USA
| | - Marilie D Gammon
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
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Susceptibility to oral cancers with CD95 and CD95L promoter SNPs may vary with the site and gender. Tumour Biol 2015; 36:7817-30. [PMID: 25944167 DOI: 10.1007/s13277-015-3516-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Accepted: 04/27/2015] [Indexed: 01/01/2023] Open
Abstract
We investigated risk association of oral cancers (tongue and buccal mucosa cancers) with FAS (-1377G > A and FAS -670 A > G) and FASL (-844 T > C) SNPs, in males and females. A case-control study of 535 oral cancer and 525 control subjects was performed. SNPs were detected in the genomic DNA isolated from peripheral blood using PCR-RFLP. We report FASL -844 T > C SNPs increased risk for buccal mucosa cancer in females but not in males. On the other hand, FAS genotypes did not alter the risk of the cancers in both females and males. However, co-occurrence of FAS -1377 GA and -670 GG, FAS -1377 AA and -670 GG genotypes, and combined genotypes of FAS and FASL (FAS -1377 AA + FAS -670 GG + FASL -844 CC) alter male susceptibility towards tongue cancer. In females, combined genotypes of FAS (-1377GA and -670 AA) were found to be a risk factor of buccal mucosa cancer (OR = 3.27, CI = 1.28-8.36; P ≤ 0.01). FASL variants (GA and AA) increased tongue cancer risk in females who were tobacco users compared to non-tobacco users. In conclusion, SNPs of the FAS and FASL might alter risk of tongue and buccal mucosa cancers differentially, in a gender-dependent manner.
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