Belaiba Fadoua, Medimegh Imene, Bidet Yannick, Boussetta Sami, Baroudi Olfa, Mezlini Amel, Bignon Yves Jean, Benammar El gaaied Amel
Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, Université de Tunis El Manar, Campus universitaire1060 El Manar I Tunis, Tunisia. Email:
Asian Pac J Cancer Prev. 2018 Oct 26;19(10):2963-2972. doi: 10.22034/APJCP.2018.19.10.2963.
The aim of this study is to investigate the involvement of consanguinity on BRCA1/2 mutation incidence in Southern Mediterranean populations and to confirm their low penetrance by comparison of their recurrence in sporadic and familial breast cancer in a context of ancient consanguinity practice. Our study comprises of two parts: First, a comparison of the consanguinity rates of the South Mediterranean countries in a relationship with the frequency of BRCA1 deleterious mutations in breast cancer families and the recurrence of these mutations. Second, we investigated 23patients with a family history of breast cancer, 51 patients without a family history of breast cancer using next-generation sequencing of BRCA2 and then confirmed by Sanger sequencing for the novel mutation. As results, we clearly show a strong relationship between the frequency of BRCA1 deleterious mutations in breast cancer families and rate of consanguinity, since they are significantly inversely correlated. Four deleterious mutations were found in BRCA2 gene including a novel frame-shift mutationc.9382_9383dup in a patient with familial breast cancer and three other frame-shift mutations c.6591_6592del, c.1310_1313del and c.7654dup in patients with sporadic breast cancer.These results are discussed in a context of selective pressure of ancient consanguinity practice. In conclusion, the study of BRCA1/2 gene in Southern Mediterranean countries revealed low penetrance recurrent mutations in sporadic and familial breast cancer. These mutations have been selected in a context of ancient consanguinity practice along with protective genetic and environmental factors.
本研究的目的是调查近亲结婚对南地中海人群中BRCA1/2基因突变发生率的影响，并通过比较散发性和家族性乳腺癌中这些突变的复发情况，在古代近亲结婚习俗的背景下确认其低外显率。我们的研究包括两个部分：第一，比较南地中海国家的近亲结婚率与乳腺癌家族中BRCA1有害突变的频率以及这些突变的复发情况。第二，我们使用BRCA2的二代测序技术对23例有乳腺癌家族史的患者和51例无乳腺癌家族史的患者进行了研究，然后通过桑格测序法对新发现的突变进行了确认。结果显示，我们清楚地表明乳腺癌家族中BRCA1有害突变的频率与近亲结婚率之间存在密切关系，因为它们呈显著负相关。在BRCA2基因中发现了四个有害突变，包括在一名家族性乳腺癌患者中发现一个新的移码突变c.9382_9383dup，以及在散发性乳腺癌患者中发现的其他三个移码突变c.6591_6592del、c.1310_1313del和c.7654dup。这些结果在古代近亲结婚习俗的选择压力背景下进行了讨论。总之，对南地中海国家BRCA1/2基因的研究揭示了散发性和家族性乳腺癌中低外显率的复发性突变。这些突变是在古代近亲结婚习俗的背景下，与保护性遗传和环境因素一起被选择出来的。
