Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome

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

doi:10.1371/journal.pone.0130018

Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome

PLoS One. 2015 Jun 8;10(6):e0130018. doi: 10.1371/journal.pone.0130018. eCollection 2015.

Authors

Affiliations

¹ School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
² Department of Public Health, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
³ Colorectal Section, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
⁴ Department of Public Health, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan.
⁵ Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
⁶ Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
⁷ School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan; Department of Public Health, China Medical University, Taichung, Taiwan.

Abstract

Background and aim: Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations.

Methods: In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence.

Results: Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55) and 0.54 (95% CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O.

Conclusion: The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adult
Colorectal Neoplasms / genetics*
Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
DNA Mismatch Repair / genetics
Demography
Diet
Female
Genetic Predisposition to Disease*
Germ-Line Mutation / genetics*
Humans
Life Style
Male
Middle Aged
Multivariate Analysis
MutL Protein Homolog 1
MutS Homolog 2 Protein / genetics*
Nuclear Proteins / genetics*
Proportional Hazards Models
Risk Factors
Taiwan

Substances

Adaptor Proteins, Signal Transducing
MLH1 protein, human
Nuclear Proteins
MSH2 protein, human
MutL Protein Homolog 1
MutS Homolog 2 Protein

Grants and funding

This study was supported by the National Sciences Council, Executive Yuan, Taiwan (grant NSC 101-2314-B-038-057). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.