Genetic Variants inXRCC2: New Insights Into Colorectal Cancer Tumorigenesis
| Autor: | D. Timothy Bishop, Jennifer Shorto, Angela Cox, Nicola J. Camp, Gillian Smith, Mark Katory, Karen Curtin, Rina George, Wei-Yu Lin, Lisa A. Cannon-Albright |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Genotype Epidemiology Colorectal cancer Single-nucleotide polymorphism medicine.disease_cause Polymorphism Single Nucleotide Article Risk Factors Internal medicine medicine Humans SNP Aged Aged 80 and over Genetics Polymorphism Genetic business.industry Case-control study Cancer Odds ratio Middle Aged medicine.disease DNA-Binding Proteins Case-Control Studies Female Colorectal Neoplasms Carcinogenesis business |
| Zdroj: | Cancer Epidemiology, Biomarkers & Prevention. 18:2476-2484 |
| ISSN: | 1538-7755 1055-9965 |
| Popis: | Polymorphisms in DNA double-strand break repair gene XRCC2 may play an important role in colorectal cancer etiology, specifically in disease subtypes. Associations of XRCC2 variants and colorectal cancer were investigated by tumor site and tumor instability status in a four-center collaboration including three U.K. case-control studies (Sheffield, Leeds, and Dundee) and a U.S. case-control study of cases from high-risk Utah pedigrees (total: 1,252 cases and 1,422 controls). The 14 variants studied were tagging single nucleotide polymorphisms (SNP) selected from National Institute of Environmental Health Sciences/HapMap data supplemented with SNPs identified from sequencing of 125 cases chosen to represent multiple colorectal cancer groups (familial, metastatic disease, and tumor subsite). Monte Carlo significance testing using Genie software provided valid meta-analyses of the total resource that includes family-based data. Similar to reports of colorectal cancer and other cancer sites, the rs3218536 R188H allele was not associated with increased risk. However, we observed a novel, highly significant association of a common SNP, rs3218499G>C, with increased risk of rectal tumors (odds ratio, 2.1; 95% confidence interval, 1.3-3.3; Pχ2 = 0.0006) versus controls, with the largest risk found for female rectal cases (odds ratio, 3.1; 95% confidence interval, 1.6-6.1; Pχ2 = 0.0006). This difference was significantly different to that for proximal and distal colon cancers (Pχ2 = 0.02). Our investigation supports a role for XRCC2 in colorectal cancer tumorigenesis, conferring susceptibility to rectal tumors. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2476–84) |
| Databáze: | OpenAIRE |
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