Service de Médecine Génique, Département de Médecine, Centre Hospitalier de l'Université de Montréal, Montreal, Canada.
Breast Cancer Res Treat. 2012 Jan;131(1):333-40. doi: 10.1007/s10549-011-1796-4. Epub 2011 Sep 27.
Specific BRCA1 and BRCA2 mutations recur in French Canadian breast and/or ovarian cancer families because of common ancestors, facilitating carrier detection in this population. We recently reported a BRCA2 c.9004G>A variant of unknown clinical significance in two French Canadian breast cancer families. It confers a E3002K alteration in the conserved C-terminus domain of BRCA2, and has been reported in non-French Canadian cancer families. Seven variant positive French Canadian families have since been identified by mutation screening of referrals to hereditary cancer clinics. In this article, we describe the cancer phenotypes of these families and further assess the contribution of this variant in the French Canadian population. We screened index breast cancer cases from 58 cancer families with at least three confirmed cases of breast and/or ovarian cancer and 960 breast cancer cases (48 years mean age) not selected for family history of cancer that were previously found not to carry the most common BRCA1 and BRCA2 mutations reported in this population. The index variant-positive cases from each family had breast cancer between the ages of 35-55 years (43 years mean age); and reported close relatives with breast cancer diagnoses between the ages of 28-84 years (57 years mean age). Three families had ovarian or peritoneal cancers. BRCA2-associated cancers, such as bladder, esophagus, pancreas, prostate, and thyroid cancers also occurred in these families. One c.9004G>A carrier also harbored the PALB2 c.2323C>T (Q775X) mutation found to recur in French Canadian breast cancer cases. No new BRCA2 variant carriers were identified in mutation screens. The absence of BRCA2 c.9004G>A carriers in the breast cancer cases not selected for family history contrasts with familial cases, supporting a pathogenic status for this variant and addition to the existing common BRCA1 and BRCA2 mutation-screening panel for French Canadian breast and/or ovarian cancer families.
特定的 BRCA1 和 BRCA2 突变由于共同的祖先在法裔加拿大乳腺癌和/或卵巢癌家族中反复出现，这使得在该人群中进行携带者检测成为可能。我们最近报道了两个法裔加拿大乳腺癌家族中 BRCA2 c.9004G>A 变异的未知临床意义。它在 BRCA2 的保守 C 末端结构域中导致 E3002K 改变，并已在非法裔加拿大癌症家族中报道。通过对遗传性癌症诊所转诊患者的突变筛查，此后又确定了 7 个变体阳性的法裔加拿大家族。在本文中，我们描述了这些家族的癌症表型，并进一步评估了该变体在法裔加拿大人群中的贡献。我们对 58 个至少有 3 例经证实的乳腺癌和/或卵巢癌病例和 960 例乳腺癌病例（平均年龄 48 岁）的索引乳腺癌病例进行了筛选，这些病例未选择有癌症家族史的病例，这些病例以前未发现该人群中最常见的 BRCA1 和 BRCA2 突变。每个家族中索引变体阳性的病例的乳腺癌发病年龄在 35-55 岁之间（平均年龄 43 岁）；并报告了近亲的乳腺癌诊断年龄在 28-84 岁之间（平均年龄 57 岁）。有 3 个家族患有卵巢癌或腹膜癌。这些家族还发生了 BRCA2 相关的癌症，如膀胱癌、食管癌、胰腺癌、前列腺癌和甲状腺癌。一名 c.9004G>A 携带者还携带了在法裔加拿大乳腺癌病例中反复出现的 PALB2 c.2323C>T（Q775X）突变。在突变筛查中未发现新的 BRCA2 变体携带者。在未选择家族史的乳腺癌病例中未发现 BRCA2 c.9004G>A 携带者与家族病例形成对比，支持该变体的致病性，并将其添加到现有的用于法裔加拿大乳腺癌和/或卵巢癌家族的常见 BRCA1 和 BRCA2 突变筛查面板中。
