Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors

P T Campbell
May 2009
Gut;May2009, Vol. 58 Issue 5, p661
Academic Journal
BACKGROUND: Germline mutations in DNA mismatch repair (MMR) genes cause Lynch syndrome colon cancers. Less understood is the risk of colon cancer associated with common polymorphisms in MMR genes and the potential interacting role of lifestyle factors known to damage DNA. METHODS: A study was conducted to examine whether MLH1 (-93G>A and Ile219Val) and MSH6 (Gly39Glu) polymorphisms were associated with risk of colon cancer in data from 1609 colon cancer cases and 1972 controls. Genotype data were further stratified by microsatellite instability status, smoking, alcohol, Western diet, alcohol and obesity, to investigate potential heterogeneity. RESULTS: The MSH6 39Glu allele was associated with increased risk of colon cancer among men (Gly/Glu or Glu/Glu vs Gly/Gly, OR 1.27; 95% CI 1.04 to 1.54). Neither MLH1 polymorphism was associated with colon cancer risk overall. When stratified by microsatellite stability status, however, the MLH1 -93A allele was associated with a more than doubling in microsatellite instability (MSI)-positive colon cancer risk (AA vs GG, OR 2.47; 95% CI 1.48 to 4.11); no associations were observed between the MMR polymorphisms examined and MSI-negative colon cancer. Statistically significant interactions were observed between: MLH1 -93G>A and smoking (MSI-negative colon cancer only, p value interaction: 0.005); and MLH1 Ile219Val and Western diet (p value interaction: 0.03). CONCLUSIONS: The MSH6 Gly39Glu and MLH1 -93G>A polymorphisms were associated with risk of overall colon and MSI-positive colon cancers, respectively. Risk for colon cancer, stratified by MMR genotype, was further modified by smoking and Western diet.


Related Articles

  • Polymorphisms in miRNA-binding sites of nucleotide excision repair genes and colorectal cancer risk. Naccarati, Alessio; Pardini, Barbara; Stefano, Landi; Landi, Debora; Slyskova, Jana; Novotny, Jan; Levy, Miroslav; Polakova, Veronika; Lipska, Ludmila; Vodicka, Pavel // Carcinogenesis;Jul2012, Vol. 33 Issue 7, p1346 

    Reduced DNA repair capacity and DNA damage accumulation may lead to cancer development. Regulation of and coordination between genes involved in DNA repair pathways is fundamental for maintaining genome stability, and post-transcriptional gene regulation by microRNAs (miRNAs) may therefore be of...

  • Red meat and poultry intake, polymorphisms in the nucleotide excision repair and mismatch repair pathways and colorectal cancer risk. Amit D. Joshi; Román Corral; Kimberly D. Siegmund; Robert W. Haile; Loïc Le Marchand; Maria Elena Martínez; Dennis J. Ahnen; Robert S. Sandler; Peter Lance; Mariana C. Stern // Carcinogenesis;Mar2009, Vol. 30 Issue 3, p472 

    Diets high in red meat have been consistently associated with colorectal cancer (CRC) risk and may result in exposure to carcinogens that cause DNA damage [i.e polycyclic aromatic hydrocarbons, heterocyclic amines (HCAs) and N-nitroso compounds]. Using a family-based study, we investigated...

  • DNA repair gene polymorphisms and tobacco smoking in the risk for colorectal adenomas. Gao, Ying; Hayes, Richard B.; Huang, Wen-Yi; Caporaso, Neil E.; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen J.; Berndt, Sonja I. // Carcinogenesis;Jun2011, Vol. 32 Issue 6, p882 

    DNA damage is thought to play a critical role in the development of colorectal adenoma. Variation in DNA repair genes may alter their capacity to correct endogenous and exogenous DNA damage. We explored the association between common single-nucleotide polymorphisms (SNPs) in DNA repair genes and...

  • DNA Repair Gene 8-Oxoguanine DNA Glycosylase Ser326Cys Polymorphism and Colorectal Cancer Risk in a Kashmiri Population. Sameer, A. Syed; Nissar, Saniya; Abdullah, Safiya; Chowdri, Nissar A.; Siddiqi, Mushtaq A. // DNA & Cell Biology;Apr2012, Vol. 31 Issue 4, p541 

    8-Oxoguanine DNA glycosylase (OGG1) is one of the important base excision repair enzymes that repair 8-oxoguanine lesion incorporated within the DNA of an individual by reactive oxygen species. The aim of this study was to detect the role of OGG1 Ser326Cys polymorphism in susceptibility to...

  • Functional variants of -1318T > G and -673C > T in c-Jun promoter region associated with increased colorectal cancer risk by elevating promoter activity. Chen, Dianke; Song, Shunxin; Lu, Jiachun; Luo, Yanxin; Yang, Zuli; Huang, Qinghua; Fu, Xinhui; Fan, Xinjuan; Wei, Yisheng; Wang, Jianping; Wang, Lei // Carcinogenesis;Jul2011, Vol. 32 Issue 7, p1043 

    C-Jun plays important roles in the development of multiple cancers, but no well-designed association studies have been conducted to assess the roles of its genetic polymorphisms in cancer risk. In a cohort of 1016 pairs of colorectal cancer (CRC) patients and matched cancer-free controls, we...

  • XRCC1 Arg399Gln polymorphism contributes to increased risk of colorectal cancer in Chinese population. Tian, Zhong; Li, Yi-Ling; Liu, Jin-Gang // Molecular Biology Reports;Jul2013, Vol. 40 Issue 7, p4147 

    Previous studies investigating the association between X-ray repair cross-complementation group 1 (XRCC1) Arg399Gln polymorphism and colorectal cancer risk in Chinese provided inconsistent findings. To assess the association in Chinese population, a meta-analysis was performed. Eligible studies...

  • Association between CYP1A2 and CYP1B1 Polymorphisms and Colorectal Cancer Risk: A Meta-Analysis. He, Xiao-Feng; Wei, Jie; Liu, Zhi-Zhong; Xie, Jian-Jun; Wang, Wei; Du, Ya-Ping; Chen, Yu; Si, Hui-Qiang; Liu, Qing; Wu, Li-Xia; Wei, Wu // PLoS ONE;Aug2014, Vol. 9 Issue 8, p1 

    Background: The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. Methodology/Principal Findings: The purpose of this study is to...

  • CASP8 -652 6N Del Polymorphism Contributes to Colorectal Cancer Susceptibility: Evidence from a Meta-Analysis. Peng, Qiliu; Lao, Xianjun; Tang, Weizhong; Chen, Zhiping; Li, Ruolin; Wang, Jian; Deng, Yan; Li, Taijie; Qin, Xue; Li, Shan // PLoS ONE;Feb2014, Vol. 9 Issue 2, p1 

    Objective: Caspase-8 (CASP8) plays a central role in the apoptotic pathway and aberrant regulation of this pathway may cause cancers. Previous studies investigating the association between CASP8 -652 6N ins/del polymorphism and colorectal cancer (CRC) risk showed inconclusive results. We...

  • TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study. Kamiza, Abram Bunya; Hsieh, Ling-Ling; Tang, Reiping; Chien, Huei-Tzu; Lai, Chih-Hsiung; Chiu, Li-Ling; Lo, Tsai-Ping; Hung, Kuan-Yi; You, Jeng-Fu; Wang, Wen-Chang; Hsiung, Chao A.; Yeh, Chih-Ching // PLoS ONE;12/1/2016, Vol. 11 Issue 12, p1 

    Background and Aim: 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...


Read the Article


Sign out of this library

Other Topics