Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk.
To evaluate the associations of breast cancer risk with polymorphisms in the XPC and XPD/ERCC2 DNA nucleotide excision repair genes, a case-control study nested within a prospective cohort of 14,274 women was conducted. Genotypes were characterized for 612 incident, invasive breast cancer cases and their 1:1 matched controls. The homozygous variant of a poly(AT) insertion/deletion polymorphism in intron 9 of the XPC gene (XPC-PAT+/+), was associated with breast cancer risk [odds ratio (OR) = 1.45, 95% confidence interval: 1.07-1.97], after adjustment for other breast cancer risk factors. The breast cancer risk associated with XPC-PAT+/+ did not differ by age at diagnosis. There was an indication of an interaction (p = 0.08) between the XPC-PAT+/+ genotype and cigarette smoking. Ever smokers with the XPC-PAT+/+ genotype were at elevated risk of breast cancer (OR = 1.56, CI: 0.95-2.58), but no differences were observed among never smokers. Analyses of the ERCC2 Lys751Gln polymorphism did not show an association with breast cancer risk, either overall or at younger ages. The results suggest that breast cancer risk is related to the XPC haplotype tagged by the XPC-PAT+/+ insertion-deletion polymorphism in intron 9. Further study of the XPC haplotypes and their interactions with smoking in relation to breast cancer risk is needed.
Shore
Roy E
RE
Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA. shore@rerf.or.jp
Zeleniuch-Jacquotte
Anne
A
Currie
Diane
D
Mohrenweiser
Harvey
H
Afanasyeva
Yelena
Y
Koenig
Karen L
KL
Arslan
Alan A
AA
Toniolo
Paolo
P
Wirgin
Isaac
I
D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D000428:Alcohol Drinking / Q000009:adverse effects; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007585:Jews / Q000235:genetics / Q000706:statistics & numerical data; D016555:Matched-Pair Analysis; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human