Journal Article

TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study

Chiu, Li-Ling, Kamiza, Abram Bunya, Tang, Reiping, Yeh, Chih-Ching, Hung, Kuan-Yi, Chien, Huei-Tzu, Hsiung, Chao A., Hsieh, Ling-Ling, Lai, Chih-Hsiung, You, Jeng-Fu, Lo, Tsai-Ping, Wang, Wen-Chang

2016

Overview

TP53 encodes p53, which has a crucial role in modulating genes that regulate defense against cancer development. This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk. We identified 260 MLH1 and MSH2 germline mutation carriers from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association of TP53 polymorphisms with CRC development. The carriers of the variant C allele of rs1042522 were associated with a decreased CRC risk (GC genotype: HR = 0.35, 95% CI = 0.14-0.86; CC genotype: HR = 0.28, 95% CI = 0.13-0.57). In addition, the dominant model of rs1042522 was associated with a decreased CRC risk (HR = 0.32, 95% CI = 0.15-0.67). The CRC risk was decreased in carriers with the CT and TT genotypes of rs12947788 (HR = 0.20, 95% CI = 0.08-0.46 and HR = 0.25, 95% CI = 0.09-0.65, respectively). Moreover, the dominant model of rs12947788 was significantly associated with a decreased CRC risk (HR = 0.21, 95% CI = 0.09-0.46). A haplotype analysis indicated that compared with the most common GC haplotype, the CT haplotype was associated with a decreased CRC risk (HR = 0.26, 95% CI = 0.11-0.59). However, no significant interaction was observed between TP53 polymorphisms and lifestyle factors. The study results revealed that the rs1042522 genotype with the C allele and the rs12947788 genotype with the T allele in TP53 were associated with a decreased CRC risk in patients with Lynch syndrome in Taiwan.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Alcohol / Alleles / Apoptosis / Biology and Life Sciences / Cancer / Care and treatment / Carriers / Cell cycle / Coffee / Cohort analysis / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - complications / Colorectal Neoplasms - genetics / Colorectal Neoplasms - pathology / Colorectal Neoplasms, Hereditary Nonpolyposis - complications / Colorectal Neoplasms, Hereditary Nonpolyposis - genetics / Colorectal Neoplasms, Hereditary Nonpolyposis - pathology / Confidence intervals / Consortia / Deoxyribonucleic acid / Development and progression / DNA / Family medical history / Female / Gene mutation / Genes / Genetic aspects / Genetic Association Studies / Genetic disorders / Genetic polymorphisms / Genetic Predisposition to Disease / Genomics / Genotype / Genotype & phenotype / Genotypes / Germ-Line Mutation / Haplotypes / Health aspects / Health risk assessment / Health risks / Health sciences / Humans / Identification methods / Lifestyles / Male / Medical research / Medicine / Medicine and Health Sciences / Middle Aged / MLH1 protein / MSH2 protein / Mutation / MutL Protein Homolog 1 - genetics / MutS Homolog 2 Protein - genetics / Nutrition / p53 Protein / Patients / Polymorphism, Single Nucleotide - genetics / Population / Public health / Retrospective Studies / Risk / Risk Factors / Studies / Surgery / Taiwan / Tumor proteins / Tumor Suppressor Protein p53 - genetics