BRAF polymorphisms and risk of melanocytic neoplasia
BRAF polymorphisms and risk of melanocytic neoplasia
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DOI：
10.1111/j.0022-202x.2005.23937.x
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发表时间：
2005-12-01
影响因子：
6.5
通讯作者：
Duffy, DL
中科院分区：
文献类型：
--
作者：
James, MR;Roth, RB;Duffy, DL
BRAF基因的体细胞突变在黑色素瘤和痣中很常见，但该基因多态性对黑色素瘤或痣易感性的贡献仍不清楚。对澳大利亚黑色素瘤病例对照样本进行BRAF基因内16个单核苷酸多态性（SNP）和3个相邻基因中5个SNP的分型。样本包括来自740个家族的755例黑色素瘤病例，根据黑色素瘤家族史分层，对照来自635个双胞胎家族（2239人）。记录病例组和对照组的面部特征，并对双胞胎进行皮肤检查，以评估全身痣计数、雀斑程度和色素沉着表型。通过引物延伸进行基因分型，然后进行基质辅助激光解吸电离-飞行时间质谱。BRAF基因中的SNP被发现与黑色素瘤状态弱相关，但与痣或雀斑的发展无关。BRAF变异导致的黑色素瘤归因风险的估计比例为1.6%。这项研究表明，BRAF多态性易患黑色素瘤，但因果变异尚未确定。与该变异相关的疾病负担大于与主要黑色素瘤易感性位点CDKN 2A相关的疾病负担，CDKN 2A的估计归因风险为0.2%。
Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6%. This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2%.