Oral Contraception Use and BRCA Penetrance: A Case-Only Study

Patrizia Pasanisi, Guy Hédelin, Jacopo Berrino, Jenny Chang-Claude, Silke Hermann, Michael Steel, Neva Haites, Jacob Hart, Ronit Peled, Lorenzo Gafà, Laura Leggio, Adele Traina, Rosalba Amodio, Maja Primic-Zakelj, Vesna Zadnik, Toomas Veidebaum, Mare Tekkel, Franco Berrino

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17 Citations (Scopus)

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).

CONCLUSION: 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.
Original languageEnglish
Pages (from-to)2107-2113
Number of pages7
JournalCancer Epidemiology, Biomarkers and Prevention
Volume18
Issue number7
Early online date23 Jun 2009
DOIs
Publication statusPublished - Jul 2009

Keywords

  • adolescent
  • adult
  • age of onset
  • BRCA2 protein
  • breast neoplasms
  • case-control studies
  • contraceptives, oral
  • Europe
  • female
  • genes, BRCA1
  • genetic predisposition to disease
  • humans
  • logistic models
  • models, genetic
  • pedigree
  • penetrance
  • questionnaires
  • risk assessment
  • risk factors
  • time factors
  • young adult

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    Pasanisi, P., Hédelin, G., Berrino, J., Chang-Claude, J., Hermann, S., Steel, M., Haites, N., Hart, J., Peled, R., Gafà, L., Leggio, L., Traina, A., Amodio, R., Primic-Zakelj, M., Zadnik, V., Veidebaum, T., Tekkel, M., & Berrino, F. (2009). Oral Contraception Use and BRCA Penetrance: A Case-Only Study. Cancer Epidemiology, Biomarkers and Prevention, 18(7), 2107-2113. https://doi.org/10.1158/1055-9965.EPI-09-0024