Department of Biogenetics, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Clinical Laboratory, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.
J Cell Mol Med. 2018 Jul;22(7):3671-3678. doi: 10.1111/jcmm.13650. Epub 2018 Apr 24.
We tested the hypothesis that genetic variation in ATM and BMI-1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer-free controls of Han nationality. This was an observational, hospital-based, case-control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy-Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005, <.001 and .001, respectively). Two variants, rs1042059 and rs201024480, in BMI-1 gene were low penetrant, with no detectable significance. After adjustment, rs189037 and rs1801516 were significantly associated with breast cancer under the additive model (OR: 1.37 and 1.52, 95% CI: 1.10-1.71 and 1.14-2.04, P: .005 and .005, respectively). In haplotype analysis, haplotypes A-C-G-G (in order of rs189037, rs3092856, rs1801516 and rs373759) and A-C-A-A in ATM gene were significantly associated with 1.98-fold and 6.04-fold increased risk of breast cancer (95% CI: 1.36-2.90 and 1.65-22.08, respectively). Nomogram analysis estimated that the cumulative proportion of 3 significant variants in ATM gene was about 12.5%. Our findings collectively indicated that ATM gene was a candidate gene in susceptibility to breast cancer in Han Chinese.
我们通过对 524 例乳腺癌病例和 518 例无癌对照的汉族人群中 6 个变体进行基因分型，检验了 ATM 和 BMI-1 基因的遗传变异是否可以通过改变乳腺癌风险的假设。这是一项观察性、基于医院的病例对照关联研究。进行了单变体、连锁、单体型、相互作用和诺模图分析。风险表示为比值比（OR）和 95%置信区间（CI）。所有研究的变体均处于哈迪-温伯格平衡且不连锁。ATM 基因中的 rs1890637、rs3092856 和 rs1801516 突变等位基因频率在病例中明显高于对照组（P =.005、<.001 和.001）。BMI-1 基因中的两个变体 rs1042059 和 rs201024480 是低外显率的，没有检测到显著意义。调整后，rs189037 和 rs1801516 在加性模型下与乳腺癌显著相关（OR：1.37 和 1.52，95%CI：1.10-1.71 和 1.14-2.04，P：.005 和.005）。在单体型分析中，ATM 基因中的单体型 A-C-G-G（按 rs189037、rs3092856、rs1801516 和 rs373759 的顺序）和 A-C-A-A 与乳腺癌风险增加 1.98 倍和 6.04 倍显著相关（95%CI：1.36-2.90 和 1.65-22.08）。诺模图分析估计 ATM 基因中 3 个显著变体的累积比例约为 12.5%。我们的研究结果表明，ATM 基因是汉族人群乳腺癌易感性的候选基因。
