title: Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut.
abstract: Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case-control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13-1.88; P=0.004), DLBCL (OR: 1.44; 95% CI: 0.99-2.09; P=0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56-0.91; P=0.007) and DLBCL (OR: 0.66; 95% CI: 0.45-0.95; P=0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA. shenmi@mail.nih.gov
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shelia H
authors.initials: SH
authors.lastname: Zahm
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Brian
authors.initials: B
authors.lastname: Leaderer
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Peter
authors.initials: P
authors.lastname: Boyle
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Zou
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003237:Connecticut; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors