de la Hoya Miguel, Fernández Juan M, Tosar Alicia, Godino Javier, Sánchez de Abajo Ana, Vidart Jose A, Pérez-Segura Pedro, Díaz-Rubio Eduardo, Caldés Trinidad
Molecular Oncology Unit, Hospital Clínico San Carlos, Madrid, Spain.
JAMA. 2003 Aug 20;290(7):929-31. doi: 10.1001/jama.290.7.929.
Defects in X-chromosome inactivation distort sex ratio in mice. The BRCA1 gene is also involved in X-chromosome inactivation, suggesting the possibility that some sex-ratio distortion may be associated with BRCA1-related human cancer syndromes.
To determine whether BRCA1 mutations are associated with distortion of the sex ratio of births in families with breast cancer, ovarian cancer, or both.
Analysis of germline mutations in participants from Spain who had been screened for BRCA between 1998 and 2002.
Sixty-eight families with at least 3 breast cancer cases or ovarian cancer cases, or both types of cancer in 2 generations (germline mutations: BRCA1, n = 17; BRCA2, n = 15; and BRCA unrelated, n = 36). An average of 4 relatives per family were tested for the corresponding BRCA mutation.
Male and female births registered in breast and/or ovarian pedigrees tested for the presence of BRCA1 and BRCA2 germline mutations.
Of BRCA1-related breast and/or ovarian cancer pedigrees, there was a 2-fold excess of female births (218 female vs 109 male births). Of BRCA2-related or BRCA-unrelated breast and/or ovarian cancer pedigrees, there was not an excess of female births (175 female/150 male and 344 female/315 male, respectively). Of 327 BRCA1 births, 218 (67%) were female births compared with 54% among BRCA2 pedigrees (175/327; P<.001) and 52% among BRCA-unrelated pedigrees (344/659; P<.001). Female births increased in the offspring of BRCA1 carriers compared with BRCA2 carriers (67% vs 52%; P =.004).
In these families with breast and/or ovarian cancer, mutations in BRCA1 but not BRCA2 were associated with a sex ratio skewed against male births.
X染色体失活缺陷会扭曲小鼠的性别比例。BRCA1基因也参与X染色体失活，这表明某些性别比例扭曲可能与BRCA1相关的人类癌症综合征有关。
确定BRCA1突变是否与乳腺癌、卵巢癌或两者兼有的家族中出生性别比例的扭曲有关。
对1998年至2002年间在西班牙接受BRCA筛查的参与者的种系突变进行分析。
68个家族，至少有3例乳腺癌病例或卵巢癌病例，或两代人中同时患有这两种癌症（种系突变：BRCA1，n = 17；BRCA2，n = 15；与BRCA无关，n = 36）。每个家族平均有4名亲属接受相应BRCA突变检测。
在检测BRCA1和BRCA2种系突变的乳腺癌和/或卵巢癌家系中登记的男女生育情况。
在与BRCA1相关的乳腺癌和/或卵巢癌家系中，女婴出生数量多出两倍（女婴218例，男婴109例）。在与BRCA2相关或与BRCA无关的乳腺癌和/或卵巢癌家系中，女婴出生数量并未过多（分别为女婴175例/男婴150例和女婴344例/男婴315例）。在327例BRCA1相关的出生中，218例（67%）为女婴，而在BRCA2家系中这一比例为54%（175/327；P<.001），在与BRCA无关的家系中为52%（344/659；P<.001）。与BRCA2携带者相比，BRCA1携带者后代中的女婴出生数量增加（67%对52%；P = 0.004）。
在这些患有乳腺癌和/或卵巢癌的家族中，BRCA1突变而非BRCA2突变与不利于男婴出生的性别比例有关。
