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Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case–control study in an Indian population

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Abstract

Purpose

Genetic polymorphisms in DNA repair genes may influence variations in individual DNA repair capacity, which could be associated with the development of cancer. We detected the distributions of three single-nucleotide polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln) in DNA repair genes, and assessed the associations of these genetic polymorphisms with colon and rectal cancer susceptibility as well as evaluated the interactions of gene–gene and gene–environment in a case–control study of an Indian population.

Methods

This case–control study was conducted with 302 cases (including 59 colon and 243 rectal cancer patients) and 291 cancer-free healthy controls. Genotypes were determined by PCR–RLFP assays. The effects [odds ratios (ORs) and 95% confidence intervals (95% CIs)] of genetic polymorphisms on colorectal cancer were estimated using unconditional logistic regression.

Results

The XRCC1 399Gln allele was found to be associated with a significantly increased rectal cancer risk among men (OR = 1.65, 95% CI 1.04–2.64). Whereas the XRCC3 241Met allele showed a protective tendency against rectal cancer (OR = 0.68, 95% CI 0.46–1.02) for both men and women. Furthermore, a combination of the XRCC1 399Gln allele with XRCC3 Thr/Thr genotype and the XPD 751Gln allele demonstrated the highest rectal cancer risk (OR = 3.52, 95% CI 1.43–9.44).

Conclusions

The combined effects of putative risk alleles/genotypes for different DNA repair pathways may strengthen the susceptibility to rectal cancer.

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Acknowledgments

The authors are very grateful to Dr. V. Shanta and Dr. T. Rajkumar (Cancer Institute, Chennai, India) for their support and generous cooperation. Jingwen Wang was also financially supported by the Ichiro Kanehara Foundation and its postdoctoral fellowship for researchers from abroad.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, 467-8601, Japan

    Jingwen Wang, Yang Zhao, Sadao Suzuki, Teruo Nagaya & Shinkan Tokudome

  2. Department of Hematology and Oncology, The First Hospital, Jilin University, Changchun, China

    Jing Jiang

  3. Epidemiological Research Center, Chennai, India

    Vendhan Gajalakshmi

  4. Hygiene and Preventive Medicine, School of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan

    Kiyonori Kuriki

  5. Health Research Foundation, Kyoto, Japan

    Seiichi Nakamura

  6. Osaka Prefectural Institute of Public Health, Osaka, Japan

    Susumu Akasaka

  7. Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Hideki Ishikawa

  8. National Institute of Health and Nutrition, Tokyo, Japan

    Shinkan Tokudome

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  1. Jingwen Wang
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  2. Yang Zhao
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Correspondence to Jingwen Wang.

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Wang, J., Zhao, Y., Jiang, J. et al. Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case–control study in an Indian population. J Cancer Res Clin Oncol 136, 1517–1525 (2010). https://doi.org/10.1007/s00432-010-0809-8

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