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Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population.

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.

SUBMITTER: Kasahara M

PROVIDER: S-EPMC2575194 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population.

Kasahara Mayumi M Osawa Kayo K Yoshida Kana K Miyaishi Aiko A Osawa Yasunori Y Inoue Natsuko N Tsutou Akimitsu A Tabuchi Yoshiki Y Tanaka Kenichi K Yamamoto Masahiro M Shimada Etsuji E Takahashi Juro J

Journal of experimental & clinical cancer research : CR 20080930

<h4>Background</h4>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.<h4>Methods</h4>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 S ...[more]

PMID: 18823566

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Project description:BackgroundThe base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent.MethodsWe searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association.ResultsA total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321, P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003-1.346, P=0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses.ConclusionsThe present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.

Dataset Information

Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population.

Publications

Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population.

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