Genetic polymorphisms in RAD23B and XPC modulate DNA repair capacity and breast cancer risk in Puerto Rican women. Issue 1 (18th June 2013)

• Record Type: Journal Article
• Authors: Pérez‐Mayoral, Julyann; Pacheco‐Torres, Alba L.; Morales, Luisa; Acosta‐Rodríguez, Heidi; Matta, Jaime L.; Dutil, Julie; Angel, Joe
• Is Part Of: Molecular carcinogenesis. Volume 52:Issue 1(2013:Jan.)
• Page Start: 127
• Page End: 138
• Publication Date: 2013-06-18
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22056
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="mc22056-sec-0001" sec-type="section"> <p>Studies have shown that DNA repair capacity (DRC) is significantly decreased in breast cancer patients, but the molecular causes of inter‐individual variation in DRC are unknown. We hypothesized that genetic variation in the nucleotide excision repair pathway genes can modulate DRC and breast cancer risk in Puerto Rican women. A total of 228 breast cancer cases and 418 controls were recruited throughout Puerto Rico. For all study participants, eight single nucleotide polymorphisms (SNPs) in the genes <italic>XPC</italic>, <italic>XPD</italic>, and <italic>RAD23B</italic> were genotyped using a TaqMan PCR, and the DRC levels of UV induced‐DNA damage was measured in peripheral lymphocytes using a host cell reactivation assay. After adjustment for confounders, <italic>RAD23B</italic> rs1805329 (Ala249Val) was found to be significantly associated with breast cancer risk under all models tested (<italic>P</italic> < 0.001). There was also a significant association between breast cancer risk and <italic>RAD23B</italic> rs10739234 (intronic) under the recessive model (<italic>P</italic> = 0.003, OR: 2.72, 95% CI: 1.40–5.30). In cases, there was a statistically significant difference in mean DRC per genotype for <italic>RAD23B</italic> rs1805329 (<italic>P</italic> < 0.001) and <italic>XPC</italic> rs2607775 (<italic>P</italic> = 0.002). When we modeled the combined effect of multiple SNPs that each independently affected DRC on cancer risk, we observed incremental augmentations in risk with increasing number of risk genotypes at those loci (<italic>P</italic> overall model <0.001). The increase in adverse genotypes was also correlated with a progressive decrease in DRC values. Our data indicate an additive effect of the NER SNPs on DRC and breast cancer risk in Puerto Rican women. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>