BRCA2 gene mutations in families with aggregations of breast and stomach cancers.
BRCA2 gene mutations in families with aggregations of breast and stomach cancers.
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乳腺癌和胃癌聚集的家族中的BRCA2基因突变。
DOI：
10.1038/sj.bjc.6600562
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发表时间：
2002-10-07
影响因子：
8.8
通讯作者：
Lubinski, J
中科院分区：
文献类型：
--
作者：
Jakubowska, A;Nej, K;Huzarski, T;Scott, R J;Lubinski, J
胃癌在全球癌症负担中仅次于肺癌。据估计，25%的家庭符合标准的遗传性弥漫性胃癌（HDCG）将有种系突变的E-钙粘蛋白基因。有证据表明，胃癌也可能是其他遗传性疾病的恶性表现。最近有报道称，胃癌的发病率在BRCA 2基因突变携带者中显著增加。我们通过直接测序分析了来自29个家族的29名乳腺癌患者的BRCA 2基因，其中至少有一名女性在50岁之前被诊断为乳腺癌，一名男性在55岁之前被诊断为胃癌。在所有这些家庭中，除了一个家庭之外，至少还有一个亲属也受到恶性肿瘤的影响。我们在6名无关患者中发现了3个移码突变和3个序列变异-潜在的错义突变，占所调查家族的20.7%（6/29）。我们的研究结果证实，BRCA 2基因突变也与乳腺癌和胃癌的家族聚集性有关。与研究人群中预期的癌症数量相比，与一般人群相比，几种癌症的代表性过高，置信区间显著，表明相关性是真实的，而不是选择性假象。英国癌症杂志（2002）87，888-891。www.bjcancer.com © 2002英国癌症研究中心
Stomach cancer ranks second to lung cancer in the global cancer burden. It is estimated that 25% of families meeting the criteria for hereditary diffuse gastric carcinoma (HDCG) will have germline mutations in the E-cadherin gene. Evidence suggests that stomach cancer might also be a malignant manifestation of other inherited predispositions to disease. Recently, it has been reported that the incidence of stomach cancer is significantly increased in BRCA2 gene mutation carriers. We analysed by direct sequencing the BRCA2 gene in 29 breast cancer patients derived from 29 families with an aggregation of at least one female breast cancer diagnosed before the age of 50 years and one male stomach cancer diagnosed before the age of 55 years. In all but one of these families at least one additional relative was also affected by a malignant tumour. We identified three frameshift mutations and three sequence variants – potentially missense mutations, in six unrelated patients representing 20.7% (six out of 29) of the families investigated. Our results confirm that BRCA2 gene mutations are also associated with familial aggregations of not only breast but also of stomach cancer. In comparison to the number of cancers expected in the study population compared to the general population there is an over-representation of several cancers with significant confidence intervals to suggest that the associations are real and not a selection artefact. British Journal of Cancer (2002) 87, 888–891. doi:10.1038/sj.bjc.6600562 www.bjcancer.com © 2002 Cancer Research UK