@article{17bcef79eca6477ba530dba694868fe0,
title = "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.",
keywords = "Colorectal cancer, Cytochrome P450, Glutathione-S-transferase, Lynch syndrome, N-acetyltransferase, Taiwan",
author = "Kamiza, {Abram Bunya} and You, {Jeng Fu} and Wang, {Wen Chang} and Reiping Tang and Chang, {Chun Yu} and Chien, {Huei Tzu} and Lai, {Chih Hsiung} and Chiu, {Li Ling} and Lo, {Tsai Ping} and Hung, {Kuan Yi} and Hsiung, {Chao A.} and Yeh, {Chih Ching}",
note = "Funding Information: List of abbreviations: CRC, colorectal cancer; MMR, mismatch repair; HCAs, heterocyclic amines; PAH, polycyclic aromatic hydrocarbon; CYP, cytochrome P450; GST, glutathione-S-transferase; NAT, N-acetyltransferase; HR, hazard ratio; CI, confidence interval; SNP, single nucleotide polymorphismAdditional Supporting Information may be found in the online version of this article. Grant sponsor: National Science Council, Executive Yuan, Taiwan; Grant number: NSC 101-2314-B-038-057. Grant sponsor: Ministry of Science and Technology, Taiwan; Grant number: MOST 104-2314-B-038-009. Grant sponsor: Taipei Medical University-National Taiwan University of Science and Technology Joint Research Program; Grant number: TMU-NTUST-104-01. Funding Information: 1School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan 2Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan 3School of Medicine, Chang Gung University, Taoyuan, Taiwan 4Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 5Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan 6Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan 7Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan 8Department of Public Health, China Medical University, Taichung, Taiwan Funding Information: We are greatly indebted to the late Ling-Ling Hsieh, who conceived and designed the experiments described in this work. Moreover, we thank all patients and their families for participating in this study, as well as the staff of Chang Gung University and Chang Gung Memorial Hospital.",
year = "2018",
doi = "10.1002/em.22113",
language = "English",
volume = "59",
pages = "69--78",
journal = "Environmental and Molecular Mutagenesis",
issn = "0893-6692",
publisher = "Wiley-Liss Inc.",
number = "1",
}
