title: Genetic polymorphisms in RAD23B and XPC modulate DNA repair capacity and breast cancer risk in Puerto Rican women.
abstract: 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 XPC, XPD, and RAD23B 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, RAD23B rs1805329 (Ala249Val) was found to be significantly associated with breast cancer risk under all models tested (P < 0.001). There was also a significant association between breast cancer risk and RAD23B rs10739234 (intronic) under the recessive model (P = 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 RAD23B rs1805329 (P < 0.001) and XPC rs2607775 (P = 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 (P 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.
authors.affiliation: Department of Biochemistry, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
authors.forename: Julyann
authors.initials: J
authors.lastname: Pérez-Mayoral
authors.forename: Alba L
authors.initials: AL
authors.lastname: Pacheco-Torres
authors.forename: Luisa
authors.initials: L
authors.lastname: Morales
authors.forename: Heidi
authors.initials: H
authors.lastname: Acosta-Rodríguez
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Matta
authors.forename: Julie
authors.initials: J
authors.lastname: Dutil
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011647:Puerto Rico; D012307:Risk Factors; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C513287:RAD23B protein, human; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes
keywords: DNA repair; breast cancer genetics; nucleotide excision repair