Savage S A, Chanock S J, Lissowska J, Brinton L A, Richesson D, Peplonska B, Bardin-Mikolajczak A, Zatonski W, Szeszenia-Dabrowska N, Garcia-Closas M
Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Br J Cancer. 2007 Sep 17;97(6):832-6. doi: 10.1038/sj.bjc.6603934. Epub 2007 Aug 14.
Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (-1381C>T, -244C>T, and Ex2-659G>A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53-1.00, 0.46-0.95 and 0.39-0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies.
端粒由TTAGGG核苷酸重复序列和位于染色体末端的蛋白质复合体组成，对维持染色体稳定性至关重要。端粒危机后的基因组不稳定可能促成乳腺癌的发病机制。许多在端粒生物学中起关键作用的基因具有有限的核苷酸多样性，因此，该途径中的单核苷酸多态性（SNP）可能会增加乳腺癌风险。在一项基于波兰1995例乳腺癌病例和2296例对照的人群研究中，对代表POT1、TEP1、TERF1、TERF2和TERT常见变异的24个SNP进行了基因分型。我们未发现个体SNP或单倍型与乳腺癌风险之间存在任何显著关联；然而，数据表明，TERT中的三个相关SNP（-1381C>T、-244C>T和Ex2-659G>A）可能与有乳腺癌家族史的个体患乳腺癌风险降低有关（优势比分别为0.73、0.66和0.57，95%置信区间分别为0.53-1.00、0.46-0.95和0.39-0.84）。总之，我们的数据不支持端粒途径基因中的SNP与乳腺癌风险之间存在实质性的总体关联。有乳腺癌家族史的女性中TERT变异的有趣关联值得在独立研究中进一步随访。
