Oral contraceptive use and BRCA penetrance: a case-only study.
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.
Pasanisi
Patrizia
P
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
Hédelin
Guy
G
Berrino
Jacopo
J
Chang-Claude
Jenny
J
Hermann
Silke
S
Steel
Michael
M
Haites
Neva
N
Hart
Jacob
J
Peled
Ronit
R
Gafà
Lorenzo
L
Leggio
Laura
L
Traina
Adele
A
Amodio
Rosalba
R
Primic-Zakelj
Maja
M
Zadnik
Vesna
V
Veidebaum
Toomas
T
Tekkel
Mare
M
Berrino
Franco
F
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
D024682:BRCA2 Protein; D003276:Contraceptives, Oral