Effect of lifestyle and reproductive factors on the onset of breast cancer in female BRCA 1 and 2 mutation carriers

• Published in: Molecular genetics & genomic medicine Vol. 4; no. 2; pp. 172 - 177
• Main Authors: Rieder, Viktoria, Salama, Mohamed, Glöckner, Lena, Muhr, Daniela, Berger, Andreas, Tea, Muy‐Kheng, Pfeiler, Georg, Rappaport‐Fuerhauser, Christine, Gschwantler‐Kaulich, Daphne, Weingartshofer, Sigrid, Singer, Christian F
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2016; John Wiley and Sons Inc
• Subjects: Age; Alcohol; Birth control; BRCA mutation; BRCA1 protein; Breast cancer; breast cancer onset; Contraceptives; Genetic counseling; Hormone replacement therapy; lifestyle factors; Lifestyles; Multivariate analysis; Mutation; Oral contraceptives; Original; Population; Pregnancy; Questionnaires; Rank tests; Regression analysis; reproductive factors; Risk factors; Smoking; Womens health; lifestyle factors; breast cancer onset; reproductive factors; BRCA mutation
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.191

Background The birth year‐dependent onset of breast cancer (BC) in BRCA1/2 mutation carriers suggests a risk‐modifying role for reproductive and life style factors. We therefore examined possible associations between these factors and age at diagnosis. Methods Cox regression analysis and log‐Rank testing were used to estimate the effect of potential life style factors on the onset of BC in 197 BRCA mutation carriers. Results Nulliparous BRCA mutation carriers developed BC earlier than those who had delivered (36.4 vs. 40.9; P = 0.001). Similarly, smokers and women who had used oral contraceptives experienced an earlier cancer onset (39.0 vs. 41.4; P = 0.05 and 39.3 vs. 44.9; P = 0.0001, respectively). In multivariate analysis, oral contraceptive use (HR: 1.7; P = 0.006) and birth cohort (< vs. ≥1965 HR: 4.5; P = 0.001) were associated with an earlier BC onset, while previous pregnancies led to a delay (HR: 0.2; P = 0.04). Mutation carriers born ≥1965 were less likely to have experienced pregnancies and more likely to have used oral contraceptives, and consequently developed BC at an earlier age (median age: 42 vs. 58; P < 0.0001 log‐Rank test). Conclusion We here demonstrate that in BRCA1/2 mutation carriers the birth cohort‐associated differences in the onset of BC are profound and influenced by reproductive factors. We here demonstrate that in BRCA1/2 mutation carriers, the birth cohort‐associated differences in the onset of breast cancer are profound and influenced by reproductive factors.