Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 630 West 168th Street, P&S 19-418, New York, NY 10032, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):219-28. doi: 10.1158/1055-9965.EPI-09-0771.
To explore the etiologic role of genetic variants in telomere pathway genes and breast cancer risk.
A population-based case-control study, the Long Island Breast Cancer Study Project, was conducted, and 1,067 cases and 1,110 controls were included in the present study. Fifty-two genetic variants of nine telomere-related genes were genotyped.
Seven single nucleotide polymorphisms (SNP) showed significant case-control differences at the level of P < 0.05. The top three statistically significant SNPs under a dominant model were TERT-07 (rs2736109), TERT-54 (rs3816659), and POT1-03 (rs33964002). The odds ratios (OR) were 1.56 [95% confidence interval (95% CI), 1.22-1.99] for the TERT-07 G-allele, 1.27 (95% CI, 1.05-1.52) for the TERT-54 T-allele, and 0.79 (95% CI, 0.67-0.95) for the POT1-03 A-allele. TERT-67 (rs2853669) was statistically significant under a recessive model; the OR of the CC genotype was 0.69 (95% CI, 0.69-0.93) compared with the T-allele. However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P < 0.001 (0.05/52) except for TERT-07. When restricted to Caucasians (94% of the study subjects), a stronger association for the TERT-07 G-allele was observed with an OR of 1.60 (95% CI, 1.24-2.05; P = 0.0002). No effect modifications were found for variant alleles and menopausal status, telomere length, cigarette smoking, body mass index status, and family history of breast cancer risk.
Four SNPs in the TERT and POT1 genes were significantly related with overall breast cancer risk. This initial analysis provides valuable clues for further exploration of the biological role of telomere pathway genes in breast cancer.
探讨端粒通路基因遗传变异与乳腺癌风险的病因学作用。
进行了一项基于人群的病例对照研究——长岛乳腺癌研究项目，共纳入 1067 例病例和 1110 例对照进行本研究。对 9 个端粒相关基因中的 52 个遗传变异进行了基因分型。
在 P<0.05 的水平上，有 7 个单核苷酸多态性（SNP）显示出显著的病例对照差异。在显性模型下，三个统计学意义上显著的 SNP 是 TERT-07（rs2736109）、TERT-54（rs3816659）和 POT1-03（rs33964002）。TERT-07 G 等位基因的比值比（OR）为 1.56（95%置信区间[95%CI]，1.22-1.99），TERT-54 T 等位基因的 OR 为 1.27（95%CI，1.05-1.52），POT1-03 A 等位基因的 OR 为 0.79（95%CI，0.67-0.95）。在隐性模型下，TERT-67（rs2853669）具有统计学意义；与 T 等位基因相比，CC 基因型的 OR 为 0.69（95%CI，0.69-0.93）。然而，在进行多重检验的 Bonferroni 校正后（P<0.001，0.05/52），除了 TERT-07 之外，没有其他 SNP 仍然具有统计学意义。当限制为白种人（研究对象的 94%）时，TERT-07 G 等位基因与更高的乳腺癌风险相关，OR 为 1.60（95%CI，1.24-2.05；P=0.0002）。未发现变异等位基因与绝经状态、端粒长度、吸烟、体重指数状态和乳腺癌风险的家族史之间存在交互作用。
TERT 和 POT1 基因中的 4 个 SNP 与总体乳腺癌风险显著相关。这项初步分析为进一步探索端粒通路基因在乳腺癌中的生物学作用提供了有价值的线索。
