SNP-A分析及TP53、MDM2、VEGF、VEGFR1、HIF1A、BRCA1风险等位基因对男性乳腺癌易感性的影响

Sarika Sharma, V. Sambyal, K. Guleria, R. Kapahi, N. Singh, M. Manjari
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引用次数: 0

摘要

男性乳腺癌(MBC)具有家族性成分,因此鉴定候选基因的多态性风险等位基因和/或细胞遗传学异常可能有助于预测MBC患者后代的风险。传统的中期细胞遗传学可以发现热点位点,而单核苷酸多态性阵列(SNP-A)分析可以发现可能在癌症病因中起作用的染色体缺陷。由于调节c-MYC、HIF1A、TP53和BRCA1信号通路的候选基因的每个等位基因的累积基因型风险可能是促进癌症发展的一个因素。通过中期细胞遗传学、SNP-A和6个基因TP53、MDM2、VEGF、VEGFR1、HIF1A和BRCA1的25个多态性分析,对一名60岁有癌症家族史的MBC患者的35岁健康儿子进行了癌症风险评估。细胞遗传学分析显示MDM2 309T > G和VEGF-417C/T多态性以及染色体不稳定性的风险基因型GG-TT, SNP-A,罕见的新生重复Yp, 7q中心点周围区域缺失表明,MBC患者的健康儿子患癌症的风险增加。
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Cancer Susceptibility for Male Breast Cancer Assessed by SNP-A Analysis and Risk Alleles of TP53, MDM2, VEGF, VEGFR1, HIF1A and BRCA1
Male Breast Cancer (MBC) has a familial component thus identification of polymorphic risk alleles of candidate genes and/or cytogenetic anomalies may help to predict the risk for the offspring of MBC patients. The conventional metaphase cytogenetics can indicate loci that are hotspots while analysis by single nucleotide polymorphism arrays (SNP-A) can identify chromosomal defects which may play a role in the etiology of cancer. A cumulative genotype risk due to each allele of candidate genes of the signaling pathways regulating c-MYC, HIF1A, TP53 and BRCA1 may be a factor facilitating cancer development. Cancer risk was assessed in a 35-year-old healthy son of a 60-year-old MBC patient with a family history of cancer by metaphase cytogenetics, SNP-A and analysis of 25 polymorphisms in six genes TP53, MDM2, VEGF, VEGFR1, HIF1A, and BRCA1. The risk genotype GG-TT of MDM2 309T > G and VEGF-417C/T polymorphisms along with chromosomal instability shown by cytogenetic analysis and SNP-A, rare de novo duplication Yp, deletion in 7q pericentromeric region indicate an increased risk of cancer in the healthy son of an MBC patient.
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