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Polymorphisms of xenobiotic‐metabolizing genes and colorectal cancer risk in patients with lynch syndrome: A retrospective cohort study in Taiwan
Author(s) -
Kamiza Abram Bunya,
You JengFu,
Wang WenChang,
Tang Reiping,
Chang ChunYu,
Chien HueiTzu,
Lai ChihHsiung,
Chiu LiLing,
Lo TsaiPing,
Hung KuanYi,
Hsiung Chao A.,
Yeh ChihChing
Publication year - 2018
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.22113
Subject(s) - hazard ratio , single nucleotide polymorphism , cyp1b1 , colorectal cancer , genotype , medicine , oncology , gstp1 , proportional hazards model , biology , gastroenterology , confidence interval , genetics , cancer , endocrinology , cytochrome p450 , gene , metabolism
Cytochrome P450 ( CYP ), glutathione‐S‐transferase ( GST ), and N‐acetyltransferase ( NAT ) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP , GST , and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR = 5.36, 95% CI = 2.39–12.0) and CYP1B1 rs1056836 CC (HR = 7.24, 95% CI = 3.51–14.9) were significantly associated with CRC risk when compared to wild‐type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR = 0.33, 95% CI = 0.12–0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic‐metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk. Environ. Mol. Mutagen. 59:69–78, 2018. © 2017 Wiley Periodicals, Inc.