Journal Article

Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses' Health Study

Jiali Han, Susan E. Hankinson, Hardeep Ranu, Immaculata De Vivo and David J. Hunter

in Carcinogenesis

Volume 25, issue 2, pages 189-195
Published in print February 2004 | ISSN: 0143-3334
Published online February 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh002
Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses' Health Study

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Genetic polymorphisms in double-strand break repair genes may influence DNA repair capacity and, in turn, confer predisposition to breast cancer. We prospectively assessed the associations of candidate polymorphisms G31479A (R188H) in XRCC2, A4541G (5′-UTR), A17893G (IVS5-14) and C18067T (T241 M) in XRCC3, and C299T (5′-UTR) and T1977C (D501D) in Ligase IV with breast cancer risk in a nested case–control study within the Nurses' Health Study (incident cases, n = 1004; controls, n = 1385). We observed no overall associations of these six genotypes with breast cancer risk. Four common haplotypes in XRCC3 accounted for 99% of the chromosomes of the present study population. We observed that Ligase IV 1977C carriers were at increased breast cancer risk if they had a first degree family history of breast cancer (test for interaction, P = 0.01). We observed that the XRCC2 R188H polymorphism modified the association of plasma α-carotene level and breast cancer risk (test for ordinal interaction, P = 0.03); the significantly decreased risk seen overall for women in the highest quartile of plasma α-carotene was only present among 188H non-carriers (the top quartile versus the bottom quartile; multivariate odds ratio, 0.55; 95% confidence interval, 0.40–0.75). No significant interactions were seen between any of these polymorphisms and duration or dose of cigarette smoking. The gene–environment interaction data suggest that the subtle effects of some of these variants on breast cancer risk may be magnified in the presence of certain exposures.

Keywords: BMI, body mass index; CI, confidence interval; DSB, double-strand breaks; HR, homologous recombination; IR, ionizing radiation; LRT, likelihood ratio test; NHEJ, non-homologous end joining; NHS, Nurses' Health Study; OR, odds ratio; SSB, single-strand breaks; SNP, single nucleotide polymorphism

Journal Article.  5666 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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