Risk Factors for Colon Cancer in Northeastern Thailand: Interaction of MTHFR Codon 677 and 1298 Genotypes with Environmental Factors

Supannee Sriamporn Promthet,Peechanika Chopjitt,Nopparat Songserm,Tipaya Ekalaksananan,Shinkan Tokudome,Chamsai Pientong,Kirati Poomphakwaen,Surapon Wiangnon,Malcolm A Moore

doi:10.2188/jea.je20090140

Abstract

BackgroundPolymorphisms in methylenetetrahydrofolate reductase (MTHFR), such as MTHFR C677T and A1298C, are associated with several cancers. This study aimed to evaluate the effects of MTHFR polymorphisms on colon cancer risk and possible interactions with environmental factors in a population from northeastern Thailand.MethodsThis hospital-based case–control study was conducted during 2002–2006; 130 colon cancer cases and 130 age- and sex-matched controls were enrolled. Information was collected and blood samples were obtained for assay of MTHFR C677T and A1298C polymorphisms by polymerase chain reaction with restriction fragment length polymorphism techniques. Associations between variables of interest and colon cancer were assessed using conditional logistic regression.ResultsIncreased risk of colon cancer was associated with alcohol consumption and bowel habits. Alcohol drinkers who consumed ≤0.50 or >0.50 units of alcohol per day had elevated risks (ORadj = 3.5; 95% CI: 1.19–10.25 and ORadj = 1.71; 95% CI: 0.74–3.96, respectively). The risk was also higher in subjects with frequent constipation (11.69; 2.18–62.79) and occasional constipation (3.43; 1.72–6.82). An interaction was observed between the MTHFR C677T polymorphism and freshwater fish consumption on colon cancer risk (P value for interaction = 0.031). Interactions were observed between the MTHFR A1298C polymorphism and bowel habits, family history of cancer, alcohol consumption, and beef consumption on colon cancer risk (P-value for interaction = 0.0005, 0.007, 0.067, 0.003, respectively).ConclusionsIn a Thai population, colon cancer risk was associated with alcohol and beef consumption, bowel habits, and family history of cancer. Interactions between MTHFR polymorphisms and environmental factors were also observed.

Highlights

In Thailand, colorectal cancer is one of the 10 most common cancers, and incidence has been increasing in both sexes in all areas during 1988–2000.1–4 The latest estimated annual incidence rate of colorectal cancer in the Thai population (1999) was 8.8 and 7.6 per 100 000 population in males and females, respectively
As part of the multicenter “International collaborative epidemiological study of host and environmental factors for stomach and colorectal cancers in Southeast Asian Countries”, we examined putative risk factors for colon cancer in a population from northeastern Thailand, with a focus on both environmental parameters and polymorphisms in methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C
Sonnenberg and Muller[39] conducted a systematic review of 9 case–control studies published before 1992, and evaluated the risk for colorectal cancer associated with self-reported constipation and bowel movement frequency: constipation was associated with a significant increase in the risk of colorectal cancer (OR, 1.48; 95% confidence intervals (95% CIs), 1.32–1.66)

Summary

Introduction

In Thailand, colorectal cancer is one of the 10 most common cancers, and incidence has been increasing in both sexes in all areas during 1988–2000.1–4 The latest estimated annual incidence rate of colorectal cancer in the Thai population (1999) was 8.8 and 7.6 per 100 000 population in males and females, respectively. A number of behavioral and environmental factors have been linked with colorectal cancer risk.[5,6,7,8,9,10,11,12,13,14,15,16] Of these, obesity, physical inactivity, and alcohol consumption have been most consistently associated with increased risk of colon cancer. Interactions were observed between the MTHFR A1298C polymorphism and bowel habits, family history of cancer, alcohol consumption, and beef consumption on colon cancer risk (P-value for interaction = 0.0005, 0.007, 0.067, 0.003, respectively). Conclusions: In a Thai population, colon cancer risk was associated with alcohol and beef consumption, bowel habits, and family history of cancer. Interactions between MTHFR polymorphisms and environmental factors were observed

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