title: Menopausal age and XRCC1 gene polymorphisms: role in breast cancer risk.
abstract: BACKGROUND
  Recent evidence that some DNA-repair functions are haploinsufficient adds weight to the notion that variants in DNA-repair genes constitute part of the spectrum of defects contributing to cancer risk. X-ray repair cross-complementing group 1 gene (XRCC1) is involved in base excision repair (BER) pathway, acting on spontaneous and induced DNA damage. This gene encodes for a scaffolding protein that brings together different proteins involved in the repair process. Among the non-synonymous polymorphisms in XRCC1 gene, codons 194 and 399 lead to amino acid changes at evolutionary conserved regions, and seem to alter the efficiency of the protein.
  
  
  METHODS
  A hospital based case-control study was carried out in a Caucasian Portuguese population (241 cancer patients and 457 controls matched for sex and age) in order to evaluate the potential modifying role of the XRCC1 polymorphisms on the individual susceptibility to breast cancer.
  
  
  RESULTS
  Our data did not reveal a positive association between the polymorphisms individually and breast cancer, or with the combination of the different genotypic associations. However, after stratification to the menopausal status, it was observed that carriers of the Gln/Gln genotype of the R399Q polymorphism with a menopausal age above 55 years are at increased risk for breast cancer (OR=4.074; CI=1.562-10.626; P=0.004). Concerning the Arg194Trp polymorphism, after stratification by menopausal status, it was observed that heterozygous individuals (Arg/Trp) with a menopausal age between 45 and 54 are at increased risk for breast cancer (adjusted OR=1.964; CI=1.174-3.288; P=0.01) as well as carriers of the variant allele (Arg/Trp+Trp/Trp) (adjusted OR=1.932; CI=1.156-3.228; P=0.012).
  
  
  CONCLUSIONS
  Our results suggest that menopausal age together with Arg194Trp and Arg399Gln XRCC1 gene polymorphisms might be involved in individual susceptibility to breast cancer.
authors.affiliation: Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Rua da Junqueira 96, P-1349-008 Lisbon, Portugal.
authors.forename: Susana N
authors.initials: SN
authors.lastname: Silva
authors.forename: Rita
authors.initials: R
authors.lastname: Moita
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Azevedo
authors.forename: Rita
authors.initials: R
authors.lastname: Gouveia
authors.forename: Isabel
authors.initials: I
authors.lastname: Manita
authors.forename: Julieta Esperança
authors.initials: JE
authors.lastname: Pina
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.forename: Jorge
authors.initials: J
authors.lastname: Gaspar
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D054458:Amplified Fragment Length Polymorphism Analysis; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011174:Portugal; D012307:Risk Factors; D044465:White People / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human