Copy number variant in the candidate tumor suppressor gene MTUS1 and familial breast cancer risk
Copy number variant in the candidate tumor suppressor gene MTUS1 and familial breast cancer risk
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DOI：
10.1093/carcin/bgm033
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发表时间：
2007-07-01
期刊：
影响因子：
4.7
通讯作者：
Burwinkel, Barbara
中科院分区：
文献类型：
--
作者：
Frank, Bernd;Bermejo, Justo Lorenzo;Burwinkel, Barbara
拷贝数变异（CNVs），插入，缺失和重复，大大有助于人类遗传变异和疾病的发展。最近的一项研究已经表征了100个CNV，包括缺少编码外显子4的线粒体肿瘤抑制基因I（MTUS 1）中的缺失。MTUS 1定位于染色体8 p，这是一个经常缺失的区域，与人类癌症（包括乳腺癌（BC））的疾病进展相关。为了研究MTUS 1 CNV对家族性BC风险的影响，我们使用病例对照研究设计分析了593例BC患者和732例对照个体。我们发现缺失变异与家族性和高风险家族性BC的风险降低显著相关（比值比（OR）= 0.58，95%置信区间（CI）= 0.37-0.90，P = 0.01和OR = 0.41，95% CI = 0.23-0.74，P = 0.003），支持其在人类癌症中的作用。据我们所知，本研究是第一个确定肿瘤抑制基因中CNV对癌症风险的影响。
Copy number variants (CNVs), insertions, deletions and duplications, contribute considerably to human genetic variation and disease development. A recent study has characterized 100 CNVs including a deletion in the mitochondrial tumor suppressor gene I (MTUS1) lacking the coding exon 4. MTUS1 maps to chromosome 8p, a region frequently deleted and associated with disease progression in human cancers, including breast cancer (BC). To investigate the effect of the MTUS1 CNV on familial BC risk, we analyzed 593 BC patients and 732 control individuals using a case-control study design. We found a significant association of the deletion variant with a decreased risk for both familial and high-risk familial BC (odds ratio (OR) = 0.58, 95% confidence interval (CI) = 0.37-0.90, P = 0.01 and OR = 0.41, 95% CI = 0.23-0.74, P = 0.003), supporting its role in human cancer. To our knowledge, the present study is the first to determine the impact of a CNV in a tumor suppressor gene on cancer risk.