Potentially functional polymorphisms in ATG10 are associated with risk of breast cancer in a Chinese population
Potentially functional polymorphisms in ATG10 are associated with risk of breast cancer in a Chinese population
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ATG10 的潜在功能多态性与中国人群患乳腺癌的风险相关
DOI：
10.1016/j.gene.2013.06.067
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发表时间：
2013-09-25
期刊：
影响因子：
3.5
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
--
作者：
Qin, Zhenzhen;Xue, Jialei;Shen, Hongbing
自噬是一种细胞过程，旨在对细胞蛋白质进行再循环以及清除细胞内的微生物，这对于在发育的关键时期以及应对营养应激时平衡能量来源非常重要。据报道，它是癌症发生和进展的一个关键过程。我们假设自噬关键基因的遗传变异可能参与乳腺癌的发生发展。因此，我们系统地筛选了六个自噬相关基因（ATG3、ATG5、ATG7、ATG10、ATG12和LC3，它们是自噬体形成的核心成分）中的14种潜在功能性多态性。我们进行了一项病例 - 对照研究，包括1064例乳腺癌病例和1073例无癌对照，以评估这些变异与乳腺癌风险的关联。我们发现ATG10中的rs1864182和rs10514231与乳腺癌风险降低显著相关[比值比（OR）= 0.77，95%置信区间（CI）：0.61 - 0.96，P = 0.023；OR = 0.75，95%CI：0.59 - 0.93，P = 0.010]。在按诊断/招募年龄、月经初潮和首次活产年龄以及绝经状态、雌激素受体（ER）和孕激素受体（PR）分层的亚组之间，观察到这两个位点具有相似的保护作用。这些结果表明，ATG10中的遗传变异可能与中国人群的乳腺癌易感性有关。需要进一步开展大规模的功能性研究来证实我们的发现。（C）2013爱思唯尔公司。保留所有权利。
Autophagy is a cellular process directed at recycling of cellular proteins and removal of intracellular microorganisms, which is important for balancing sources of energy at critical times in development and in response to nutrient stress. It has been reported to be a critical process in cancer initiation and progression. We hypothesized that genetic variants in critical genes of autophagy may be involve in the development of breast cancer. Thus, we systematically screened 14 potentially functional polymorphisms in six autophagy-related genes (ATG3, ATG5, ATG7, ATG10, and ATG12 and LC3) that are core components in autophagosome formation. We conducted a case-control study including 1064 breast cancer cases and 1073 cancer-free controls to evaluate the associations of these variants with breast cancer risk. We found that rs1864182 and rs10514231 in ATG10 were significantly associated with a decreased risk of breast cancer [odds ratios (OR) = 0.77, 95% confidence interval (Cl): 0.61-0.96, P = 0.023; and OR = 0.75, 95% CI: 0.59-0.93, P = 0.010, respectively]. Similar protective effects for both loci were observed between subgroups stratified by ages at diagnosis/recruitment, menarche and first live birth, and status of menopause, estrogen receptor (ER) and progesterone receptor (PR). These results suggest that genetic variants in ATG10 may implicate with breast cancer susceptibility in Chinese population. Further large and functional studies are needed to confirm our findings. (C) 2013 Elsevier B.V. All rights reserved.