Journal Article

Single nucleotide polymorphisms in the <i>EXO1</i> gene and risk of colorectal cancer in a Japanese population

Hiromasa Yamamoto, Hiroko Hanafusa, Mamoru Ouchida, Masaaki Yano, Hiromitsu Suzuki, Masakazu Murakami, Motoi Aoe, Nobuyoshi Shimizu, Kei Nakachi and Kenji Shimizu

in Carcinogenesis

Volume 26, issue 2, pages 411-416
Published in print February 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh335
Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population

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EXO1 is a member of the RAD2 nuclease family and functions in DNA replication, repair and recombination. We investigated the 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, the 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 1.23–4.56) demonstrated significant association with the development of colorectal cancer after adjusting for age, gender and smoking status. For P757L, patients with the Leu/Leu genotype showed a reduced risk of colorectal cancer (adjusted OR = 0.398, 95% CI 0.183–0.866) when the Pro/Leu and Pro/Pro genotypes were combined and used as the reference. The Leu/Leu genotype also had a reduced risk (adjusted OR = 0.373, 95% CI 0.164–0.850) when the Pro/Leu genotype was used 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 a higher frequency of MSI positives than those from patients who carried both low risk genotypes, although a significant correlation was not found between EXO1 genotype 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 clinicopathological characteristics in colorectal cancer patients.

Keywords: CI, confidence interval; EXO1, exonuclease 1; HNPCC, hereditary non-polyposis colorectal cancer; MMR, mismatch repair; MSI, microsatellite instability; MSI-H, MSI high; MSI-L, MSI low; MSS, microsatellite stable; OR, odds ratio; RFLP, restriction fragment length polymorphism; SNP, single nucleotide polymorphism; TNM, UICC Tumor–Node–Metastasis classification

Journal Article.  4286 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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