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Open Access Research article

Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study

Camilla Furu Skjelbred12, Mona Sæbø2, Håkan Wallin3, Bjørn Andersen Nexø4, Per Christian Hagen2, Inger Marie Bowitz Lothe5, Steinar Aase6, Egil Johnson7, Inger-Lise Hansteen1, Ulla Vogel3 and Elin H Kure25*

Author Affiliations

1 Department of Laboratory Medicine, Section of Medical Genetics, Telemark Hospital, N-3710 Skien, Norway

2 Telemark University College, Faculty of Arts and Sciences, Department of Environmental and Health Studies, Hallvard Eikas plass, N-3800 Bø i Telemark, Norway

3 National Institute of Occupational Health, Copenhagen, Denmark

4 Institute of Human Genetics, University of Aarhus, Aarhus, Denmark

5 Department of Pathology, Ullevaal University Hospital, Oslo, Norway

6 Department of Pathology, The Gade Institute, Haukeland University Hospital / University of Bergen, N-5021 Bergen, Norway

7 Department of Gastroenterological Surgery, Ullevaal University Hospital, Oslo, Norway

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BMC Cancer 2006, 6:67  doi:10.1186/1471-2407-6-67

Published: 16 March 2006

Abstract

Background

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 Arg194Trp, Arg280His, Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln), 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 Arg280His polymorphism and a reduced risk associated with the XRCC1 Arg399Gln polymorphism. Interestingly, individuals with the XPD Lys751Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas.