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Variation in DNA Repair Genes ERCC2, XRCC1, and XRCC3 and Risk of Follicular Lymphoma

¹ Department of Medical Epidemiology and Biostatistics and ² Microbiology and Tumor Biology Center, Karolinska Institutet; ³ Swedish Institute for Infectious Disease Control; ⁴ Department of Mathematical Statistics, Stockholm University; ⁵ Department of Pathology and Oncology, Karolinska University Hospital, Stockholm, Sweden; ⁶ Department of Biosciences at Novum and Clinical Research Centre, Karolinska Institutet, Huddinge, Sweden; ⁷ Department of Epidemiology Research, Statens Serum Institut; ⁸ Tissue Typing Laboratory, Rigshospitalet, Copenhagen, Denmark; ⁹ Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden; ¹⁰ Department of Oncology, Radiology, and Clinical Immunology, Akademiska Hospital, Uppsala, Sweden; and ¹¹ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

Requests for reprints: Karin Ekström Smedby, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden. Phone: 591-2-277-15-80; Fax: 591-2-243-49-26. E-mail: karin.ekstrom{at}meb.ki.se

The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms. (Cancer Epidemiol Biomarkers Prev 2006;15(2)–65)

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