Author(s): Kasahara M, Osawa K, Yoshida K, Miyaishi A, Osawa Y,
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Abstract BACKGROUND: Genetic polymorphisms of DNA repair enzymes may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interactions between polymorphisms of repair genes and tobacco smoking in colorectal cancer. METHODS: The case-control study involved sixty-eight colorectal cancer patients and 121 non-cancer controls divided into non-smokers and smokers according to pack-years of smoking. The genetic polymorphisms of DNA repair enzymes,OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu and XRCC1 Arg399Gln, were examined using PCR-RFLP. RESULTS: The MUTYH Gln324His showed strong significant associations with a risk of colorectal cancer (crude odds ratio [OR] 3.30, 95\% confidence interval [95\%CI] 1.44-7.60, p = 0.005; adjusted OR3.53, 95\%CI 1.44-8.70, p = 0.006). The ORs for the APEX1 Asp148Glu were statistically significant (crude OR 2.69, 95\%CI 1.45-4.99, p = 0.002; adjusted OR 2.33, 95\%CI 1.21-4.48, p = 0.011). The ORs for the MUTYH Gln324His and the APEX1 Asp148Glu were statistically significant for colon cancer (adjusted OR 3.95, 95\%CI 1.28-12.20, p = 0.017 for MUTYH Gln324His ; adjusted OR 3.04, 95\%CI 1.38-6.71, p = 0.006 for APEX1 Asp148Glu). The joint effect of tobacco exposure and the MUTYH Gln324His showed a significant association with colorectal cancer risk in non-smokers (adjusted OR 4.08, 95\%CI 1.22-13.58, p = 0.022) and the APEX1 Asp148Glu was significantly increased in smokers (adjusted OR 5.02, 95\%CI 1.80-13.99, p = 0.002). However, the distributions of OGG1 Ser326Cys and XRCC1 Arg399Gln were not associated with a colorectal cancer risk. CONCLUSION: Our findings suggest that the MUTYH Gln324His and the APEX1 Asp148Glu constitutes an increased risk of colorectal cancer, especially colon cancer. The MUTYH Gln324His is strongly associated with colorectal cancer susceptibility in never smoking history, whereas the APEX1 Asp148Glu genotype constitutes an increased risk of colorectal cancer when accompanied by smoking exposure.
This article was published in J Exp Clin Cancer Res
and referenced in Hereditary Genetics: Current Research