Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009
Oral contraceptive use and BRCA penetrance: a case-only study.
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Pasanisi Patrizia, Hédelin Guy, Berrino Jacopo, Chang-Claude Jenny, Hermann Silke, Steel Michael, Haites Neva, Hart Jacob, Peled Ronit, Gafà Lorenzo, Leggio Laura, Traina Adele, Amodio Rosalba, Primic-Zakelj Maja, Zadnik Vesna, Veidebaum Toomas, Tekkel Mare, Berrino Franco
Аннотация
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.
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.