title: Oral contraceptive use and BRCA penetrance: a case-only study.
abstract: BACKGROUND
  Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer.
  
  
  METHODS
  We recruited 3,123 patients diagnosed with breast cancer before the age of 45 years. Participants were classified according to their probability of carrying a BRCA mutation on the basis of their family history of breast and ovarian cancer. According to a case-only approach, the frequency of relevant exposures among breast cancer cases with high probability of BRCA mutation ("genetic cases") was compared with the frequency of the same exposures among breast cancer cases with a low probability of BRCA mutation ("sporadic cases"). The interaction odds ratios (OR) and 95% confidence intervals (CI) for oral contraceptive use were estimated by unconditional logistic regression, after controlling for potentially confounding variables.
  
  
  RESULTS
  The analysis was carried out comparing 382 "genetic" and 1,333 "sporadic" cases. We found a borderline significant interaction between genetic breast cancer and oral contraceptive use for ever users compared with never users (OR, 1.3; 95% CI, 1.0-1.7). The greatest interaction OR was found for women who started using pill at 18 to 20 years (OR, 1.6; 95% CI, 1.1-2.3).
  
  
  CONCLUSIONS
  These results suggest that BRCA mutation carriers, as well as women with a significant family history of breast and ovarian cancer are more vulnerable to exogenous hormones in oral contraceptives.
authors: Department of Preventive and Predictive Medicine, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milano, Italy. patrizia.pasanisi@istitutotumori.mi.it
authors: Patrizia
authors: P
authors: Pasanisi
authors: Guy
authors: G
authors: Hédelin
authors: Jacopo
authors: J
authors: Berrino
authors: Jenny
authors: J
authors: Chang-Claude
authors: Silke
authors: S
authors: Hermann
authors: Michael
authors: M
authors: Steel
authors: Neva
authors: N
authors: Haites
authors: Jacob
authors: J
authors: Hart
authors: Ronit
authors: R
authors: Peled
authors: Lorenzo
authors: L
authors: Gafà
authors: Laura
authors: L
authors: Leggio
authors: Adele
authors: A
authors: Traina
authors: Rosalba
authors: R
authors: Amodio
authors: Maja
authors: M
authors: Primic-Zakelj
authors: Vesna
authors: V
authors: Zadnik
authors: Toomas
authors: T
authors: Veidebaum
authors: Mare
authors: M
authors: Tekkel
authors: Franco
authors: F
authors: Berrino
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects*; D005060:Europe / Q000453:epidemiology; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008957:Models, Genetic; D010375:Pedigree; D019683:Penetrance; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult
chemical_list: D024682:BRCA2 Protein; D003276:Contraceptives, Oral