A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population.
A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population.
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DOI：
10.1186/1471-2407-9-245
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发表时间：
2009-07-20
期刊：
影响因子：
3.8
通讯作者：
Monne M
中科院分区：
文献类型：
--
作者：
Palomba G;Loi A;Uras A;Fancello P;Piras G;Gabbas A;Cossu A;Budroni M;Contu A;Tanda F;Farris A;Orrù S;Floris C;Pisano M;Lovicu M;Santona MC;Landriscina G;Crisponi L;Palmieri G;Monne M
近年来，许多研究评估了不同队列中BRCA 1和BRCA 2基因生殖系突变的患病率。我们在这里广泛调查了BRCA 1 -2突变在整个遗传同质撒丁岛人群中的患病率和地理分布。还评价了可能预测BRCA 1 -2生殖系突变存在的表型特征的发生。通过DHPLC分析和DNA测序，对348例浸润性乳腺癌或卵巢癌家族性复发且至少有两名家族成员受累的乳腺癌患者进行BRCA 1 -2突变筛查。通过Pearson卡方检验评估BRCA 1和BRCA 2突变状态与临床和病理参数的相关性。总体而言，在35/348（10%）个家族中检测到8个BRCA 1和5个BRCA 2有害突变;大多数（23/35;66%）突变在BRCA 2基因中发现。BRCA 1 -2突变的地理分布与撒丁岛的三个特定的大区域有关，反映了其古老的历史：a）北方地区，语言上不同于岛上的其他地区（其中具有奠基者效应的BRCA 2 c.8764_8765delAG突变是主要的）; B）中部地区，古代撒丁岛人口的土地（其中BRCA 2突变仍然比BRCA 1突变更常见）;以及c）西南部地区，有许多腓尼基和迦太基地区（BRCA 1突变普遍存在）。我们还发现，表型特征，如高肿瘤分级和缺乏雌激素/孕激素受体的表达，以及诊断时的年龄和家族中卵巢癌的存在，可能预示着BRCA 1 -2生殖系突变的存在。
In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.
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DOI：
10.1093/jnci/91.11.943
发表时间：
1999-06-02
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Peto, J;Collins, N;Stratton, MR
通讯作者：
Stratton, MR
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
HLA II 类单倍型的区域间分布表明撒丁岛人群适合复杂疾病的病例对照关联研究
影响因子：
3.5
作者：
Lampis, R;Morelli, L;Cucca, F
通讯作者：
Cucca, F
华蓥山乳腺癌-卵巢癌家族中 BRCA1 基因的创始人突变
影响因子：
9.8
作者：
Górski, B;Byrski, T;Lubinski, J
通讯作者：
Lubinski, J
影响因子：
3.8
作者：
Russo, Antonio;Calo, Valentina;Bazan, Viviana
通讯作者：
Bazan, Viviana