In:
BMC Cancer, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2006-12)
Abstract:
Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1 , XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively. Methods We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls) to test the association between five polymorphisms in these DNA repair genes ( XRCC1 Arg 194 Trp, Arg 280 His, Arg 399 Gln, XRCC3 Thr 241 Met and XPD Lys 751 Gln), and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption. Results The XRCC1 280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19–4.46). The XRCC1 399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41–0.96). Carriers of the variant XPD 751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03–1.89), while no association was found with risk of carcinomas. Conclusion Our results suggest an increased risk for advanced colorectal neoplasia in individuals with the XRCC1 Arg 280 His polymorphism and a reduced risk associated with the XRCC1 Arg 399 Gln polymorphism. Interestingly, individuals with the XPD Lys 751 Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas.
Type of Medium:
Online Resource
ISSN:
1471-2407
DOI:
10.1186/1471-2407-6-67
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2006
detail.hit.zdb_id:
2041352-X
Bookmarklink