Low-frequency nonsynonymous variants in FKBPL and ARPC1B genes are associated with breast cancer risk in Chinese women

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• 作者：Wen Zhou ; Yue Jiang ; Meng Zhu ; Dong Hang ; Jiaping Chen ; Jing Zhou ; Juncheng Dai ; Hongxia Ma ; Zhibin Hu ; Guangfu Jin ; Jiahao Sha and Hongbing Shen
• 刊名：Molecular Carcinogenesis
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：56
• 期：2
• 页码：774-780
• 全文大小：517K
• ISSN：1098-2744

文摘

Genome-wide association studies have reported more than 100 independent common loci associated with breast cancer risk. The contribution of low-frequency or rare variants to breast cancer susceptibility has not been well explored. Thus, we applied exome chip to genotype >200 000 low-frequency and rare variants in 1064 breast cancer cases and 1125 cancer-free controls and subsequently validated promising associations in another 1040 breast cancer cases and 1240 controls. We identified two low-frequency nonsynonymous variants at FKBPL (rs200847762, OR = 0.34, 95% CI = 0.20–0.57, P = 4.31 × 10⁻⁵) and ARPC1B (rs1045012, OR = 0.56, 95% CI = 0.43–0.74, P = 4.30 × 10⁻⁵) associated with breast cancer risk. In stratification analyses, we found that the protective effect of rs200847762 was stronger in ER-positive breast cancer (OR = 0.18, 95% CI = 0.06–0.42) than that in ER-negative one (OR = 0.59, 95% CI = 0.31–1.05). Our findings indicate that low-frequency variants may also contribute to breast cancer susceptibility and genetic variants in 6p21.33 and 7q22.1 are important in breast carcinogenesis.