Carcinogenesis Advance Access published online on November 18, 2004
Carcinogenesis, doi:10.1093/carcin/bgh335
© 2004 by Oxford University Press
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1 Department of Cancer and Thoracic Surgery, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan; Department of Molecular Genetics, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
* To whom correspondence should be addressed. EXO1 is a member of the RAD2 nuclease family, and functions in DNA replication, repair and recombination. We investigated relationship of single nucleotide polymorphisms (SNPs) at exon 10 (T439M) and exon 13 (P757L) of the EXO1 gene with development, progression and metastasis of colorectal cancer. For T439M, Thr/Met genotype (odds ratio (OR) = 2.03, 95% confidence interval (CI), 1.04-3.98), and Thr/Met and Met/Met genotypes combined (OR = 2.37, 95% CI, 1.237-4.56) demonstrated significant association with the development of colorectal cancer after adjusting for age, gender and smoking status. For P757L, the patients with Leu/Leu genotype showed risk reduction of colorectal cancer (adjusted OR = 0.398, 95% CI, 0.183-0.866) when Pro/Leu and Pro/Pro genotypes were combined and used as the reference. Leu/Leu genotypes still had risk reduction (adjusted OR = 0.373, 95% CI, 0.164-0.850) when Pro/Leu genotype was defined as the reference. Individuals who carried both putative risk genotypes (Thr/Met and Met/Met for T439M and Pro/Leu for P757L) showed an adjusted OR of 4.95 (95% CI, 1.56-15.7) compared with those who carried both low-risk genotypes. Analysis of microsatellite instability (MSI) revealed that tumors from individuals who carried both putative risk genotypes tended to have higher frequency of MSI-positives than those from patients who carried both low-risk genotypes although a significant correlation was not found between EXO1 genotypes and MSI status. This is the first report to provide evidence for an association of EXO1 gene polymorphisms with colorectal cancer risk. The EXO1 genotypes were not associated with any clinicopathologic characteristics in colorectal cancer patients.
Revised October 15, 2004
Accepted November 7, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population
2 Department of Molecular Genetics, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
3 Department of Cancer and Thoracic Surgery, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
4 Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815, Japan
Kenji Shimizu, E-mail: shimke47{at}md.okayama-u.ac.jp
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