Milne Roger L, Osorio Ana, Cajal Teresa Ramón Y, Vega Ana, Llort Gemma, de la Hoya Miguel, Díez Orland, Alonso M Carmen, Lazaro Conxi, Blanco Ignacio, Sánchez-de-Abajo Ana, Caldés Trinidad, Blanco Ana, Graña Begoña, Durán Mercedes, Velasco Eladio, Chirivella Isabel, Cardeñosa Eva Esteban, Tejada María-Isabel, Beristain Elena, Miramar María-Dolores, Calvo María-Teresa, Martínez Eduardo, Guillén Carmen, Salazar Raquel, San Román Carlos, Antoniou Antonis C, Urioste Miguel, Benítez Javier
Unidad de Genotipación-CEGEN and Grupo de Genética Humana, Programa de Genética del Cáncer Humano, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
Clin Cancer Res. 2008 May 1;14(9):2861-9. doi: 10.1158/1078-0432.CCR-07-4436.
It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general population is considerably lower, the prevalence of BRCA2 mutations seems to be higher, and a distinct spectrum of recurrent mutations exists for both genes. We aimed to estimate these penetrances for women attending genetic counseling units in Spain.
We collected phenotype and genotype data on 155 BRCA1 and 164 BRCA2 mutation carrier families from 12 centers across the country. Average age-specific cumulative risks of breast cancer and ovarian cancer were estimated using a modified segregation analysis method.
The estimated average cumulative risk of breast cancer to age 70 years was estimated to be 52% [95% confidence interval (95% CI), 26-69%] for BRCA1 mutation carriers and 47% (95% CI, 29-60%) for BRCA2 mutation carriers. The corresponding estimates for ovarian cancer were 22% (95% CI, 0-40%) and 18% (95% CI, 0-35%), respectively. There was some evidence (two-sided P = 0.09) that 330A>G (R71G) in BRCA1 may have lower breast cancer penetrance.
These results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCA2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations. Carriers should be fully informed of their mutation- and age-specific risks to make appropriate decisions regarding prophylactic interventions such as oophorectomy.
在西班牙等国家，普通人群中乳腺癌发病率相当低，BRCA2突变的患病率似乎更高，且这两个基因存在不同的复发性突变谱，目前尚不清楚已发表的BRCA1和BRCA2基因突变的乳腺癌和卵巢癌外显率估计值是否可用于遗传咨询。我们旨在估计西班牙遗传咨询机构中女性的这些外显率。
我们收集了来自全国12个中心的155个BRCA1突变携带者家庭和164个BRCA2突变携带者家庭的表型和基因型数据。使用改良的分离分析方法估计乳腺癌和卵巢癌的年龄特异性平均累积风险。
BRCA1突变携带者至70岁时乳腺癌的估计平均累积风险为52%[95%置信区间（95%CI），26 - 69%]，BRCA2突变携带者为47%（95%CI，29 - 60%）。卵巢癌的相应估计值分别为22%（95%CI，0 - 40%）和18%（95%CI，0 - 35%）。有证据表明（双侧P = 0.09），BRCA1基因中的330A>G（R71G）可能具有较低的乳腺癌外显率。
这些结果与最近对几乎所有先前外显率研究的荟萃分析结果一致，表明在西班牙接受遗传咨询服务的BRCA1和BRCA2基因突变女性患乳腺癌和卵巢癌的风险与其他白种人群发表的风险相似。携带者应充分了解其特定突变和年龄相关的风险，以便就预防性干预措施（如卵巢切除术）做出适当决策。
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