Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers
Por:
Milne, RL, Osorio, A, Cajal, TRY, Baiget, M, Lasa, A, Diaz-Rubio, E, de la Hoya, M, Caldes, T, Teule, A, Lazaro, C, Blanco, I, Balmana, J, Sanchez-Olle, G, Vega, A, Blanco, A, Chirivella, I, Cardenosa, EE, Duran, M, Velasco, E, de Duenas, EM, Tejada, MI, Miramar, MD, Calvo, MT, Guillen-Ponce, C, Salazar, R, Roman, CS, Urioste, M, Benitez, J
Publicada:
1 ene 2010
Resumen:
Environmental or lifestyle factors are likely to explain part of the heterogeneity in breast and ovarian cancer risk among BRCA1 and BRCA2 mutation carriers. We assessed parity as a risk modifier in 515 and 503 Spanish female carriers of mutations in BRCA1 and BRCA2, respectively. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were estimated using weighted Cox proportional hazards regression, adjusted for year of birth and study centre. The results for ever being parous and number of live-births were very similar for carriers of mutations in both genes. For all mutation carriers combined, the estimated HR associated with ever having had a live-birth was 0.74 (95% confidence interval [CI] = 0.55-1.01, P = 0.06), and that associated with each live-birth was 0.87 (95%CI = 0.77-0.98, P = 0.02). The latter association was observed only in women aged 40 and above (HR = 0.81, 95%CI = 0.70-0.94, P = 0.004 vs. HR = 0.99, 95%CI = 0.83-1.18, P = 0.9 for women under age 40), and this trend was highly consistently observed for carriers of mutations in each gene. There was no evidence of an association between breast cancer risk and age at first birth for parous BRCA1 or BRCA2 mutation carriers (P-trend a parts per thousand yen 0.3). The power to detect associations with ovarian cancer risk was much lower, especially for BRCA2 mutation carriers. Nevertheless, having a live-birth was associated with protection for BRCA1 mutation carriers (HR = 0.41, 95%CI = 0.18-0.94, P = 0.03), and a strong and consistent protective effect of age at first birth was observed for parous carriers of mutations in both genes (HR = 0.65, 95%CI = 0.52-0.83, P < 0.001). This is the third independent study to find that, as in the general population, parity appears to be associated with protection from breast cancer in women with mutations in BRCA1 and BRCA2. Parity appears to be protective for ovarian cancer in BRCA1 mutation carriers, but its role in BRCA2 mutation carriers remains unclear. Whether later age at first birth is also protective for ovarian cancer in mutation carriers requires further confirmation.
Filiaciones:
Milne, RL:
CNIO, Programa Genet Canc Humano, Grp Epidemiol Genet & Mol, Madrid 28029, Spain
Osorio, A:
CNIO, Programa Genet Canc Humano, Grp Genet Humana, Madrid 28029, Spain
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Med Oncol Serv, Barcelona, Spain
Baiget, M:
Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona, Spain
Lasa, A:
Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona, Spain
Diaz-Rubio, E:
Hosp Clin San Carlos, Med Oncol Serv, Madrid, Spain
de la Hoya, M:
Hosp Clin San Carlos, Oncol Mol Lab, Madrid, Spain
Caldes, T:
Hosp Clin San Carlos, Oncol Mol Lab, Madrid, Spain
Teule, A:
Inst Catalan Oncol IDIBELL, Programa Consejo Genet Canc, Barcelona, Spain
Lazaro, C:
Inst Catalan Oncol IDIBELL, Programa Diagnost Mol Canc Hereditario, Barcelona, Spain
Blanco, I:
Inst Catalan Oncol IDIBELL, Programa Consejo Genet Canc, Barcelona, Spain
Balmana, J:
Hosp Valle De Hebron, Dept Med Oncol, Breast Canc Ctr, Barcelona, Spain
Sanchez-Olle, G:
Hosp Valle De Hebron, Dept Med Oncol, Breast Canc Ctr, Barcelona, Spain
Vega, A:
CIBER ER, Grp Med Xen USC, Santiago De Compostela, Galicia, Spain
SERGAS, Fdn Publ Galega Med Xen, Santiago De Compostela, Galicia, Spain
Blanco, A:
CIBER ER, Grp Med Xen USC, Santiago De Compostela, Galicia, Spain
SERGAS, Fdn Publ Galega Med Xen, Santiago De Compostela, Galicia, Spain
Chirivella, I:
Hosp Clin Univ Valencia, Valencia, Spain
Grp Canc Hereditario Comunidad Valenciana, Valencia, Spain
Cardenosa, EE:
Grp Canc Hereditario Comunidad Valenciana, Valencia, Spain
de Duenas, EM:
Grp Canc Hereditario Comunidad Valenciana, Valencia, Spain
Consorcio Hosp Prov Castello, Castellon de La Plana, Spain
Tejada, MI:
Hosp Cruces, Genet Mol Lab, Barakaldo Bizkaia, Spain
Miramar, MD:
Hosp Univ Miguel Server, Serv Bioquim Clin, Secc Genet Med, Zaragoza, Spain
Calvo, MT:
Hosp Univ Miguel Server, Serv Bioquim Clin, Secc Genet Med, Zaragoza, Spain
Guillen-Ponce, C:
Grp Canc Hereditario Comunidad Valenciana, Valencia, Spain
Hosp Univ Elche, Unidad Consejo Genet Canc, Alicante, Spain
Salazar, R:
Univ Salamanca, Ctr Invest Canc, E-37008 Salamanca, Spain
Roman, CS:
Hosp Univ Ramon y Cajal, Serv Genet Med, Madrid, Spain
Urioste, M:
CNIO, Programa Genet Canc Humano, Grp Genet Humana, Madrid 28029, Spain
CIBER ER, Madrid, Spain
Benitez, J:
CNIO, Programa Genet Canc Humano, Grp Genet Humana, Madrid 28029, Spain
CIBER ER, Madrid, Spain
Open Access
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