Polymorphisms of xenobiotic-metabolizing genes and colorectal cancer risk in patients with lynch syndrome: A retrospective cohort study in Taiwan.

Abstract:

: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.

journal_name

Environ Mol Mutagen

authors

Kamiza AB,You JF,Wang WC,Tang R,Chang CY,Chien HT,Lai CH,Chiu LL,Lo TP,Hung KY,Hsiung CA,Yeh CC

doi

10.1002/em.22113

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

69-78

issue

1

eissn

0893-6692

issn

1098-2280

journal_volume

59

pub_type

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