Assessing the variations in breast/ovarian cancer risk for Chinese BRCA1/2 carriers

• DOI: 10.1101/2020.07.20.20135202
• Publication Date: 2020-07-26T16:17:55Z
• Authors: Ang Li; Yi Zi; Jiaqi Luo; Xiaobin You; Zhaoji Lan; Tianliangwen Zhou; Yangming Wu; Qihuan Zhi; Huijun Su; Mei Zhu; Siwen Xu; Yun Gao; Zaixuan Zhong; Ling Xie; Yuanqin Wang; Qiuping Lin; Xiaoting Li; Jiamin Zhan; Hui Weng; Dan Li; Shulan Xu; Gang Sun; Yujian Shi
• Keywords: Penetrance

Abstract Background Cancer risks vary in different BRCA1/2 mutations. Previous studies based on Caucasian population have identified regions associated with elevated/reduced of breast/ovarian cancers. Since ethnic differences are known to affect mutation spectra, we interested defining Chinese-specific ovarian/breast cancer cluster (OCCR/BCCR) and comparing previously reported Caucasian-based regions. We also aim characterize the distribution estimate Chinese recurrent Methods 7,919 (3,641 unselected cancer-free women + 4,278 female patients) individuals were included study. Germline status detected amplicon-based next-generation sequencing. carriers defined as bearing likely pathogenic or calculated odds ratio (OR) breast OR ovarian cancer, their two ORs (ROR) for each region. ROR > 1 indicated elevated and/or decreasing cancer; < increasing odds. The frequency, penetrance six founder mutations respectively. Haplotype analysis age estimation performed most prevalent widely-spread BRCA1:c.5470_5477del. Results A total 729 subjects germline deleterious mutations, including 236 BRCA1 122 BRCA2 putative OCCR/BCCR partially overlapped shared structural-functional characteristics. greatly both penetrance. estimated convey low penetrance, while area-restricted seemed confer higher nearly complete BRCA1:c.5470_5477del accounting 9.5% - 18% is emerged ∼2,090 years ago (70 B.C.) during Han Dynasty, about 290 (∼14.5 generations) prior Three Kingdoms Period when a major migration occurred. Conclusion genotypes significantly risks. Hence ideally risk assessment should be mutation-specific, rather than concerning single figure. probably ancient may originated more 2,000 ago.