Data from Multiple Genetic Variants in Telomere Pathway Genes and Breast Cancer Risk

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<div>Abstract<p><b>Purpose:</b> To explore the etiologic role of genetic variants in telomere pathway genes and breast cancer risk.</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> Seven single nucleotide polymorphisms (SNP) showed significant case-control differences at the level of <i>P</i> < 0.05. The top three statistically significant SNPs under a dominant model were <i>TERT-07</i> (rs2736109), <i>TERT-54</i> (rs3816659), and <i>POT1-03</i> (rs33964002). The odds ratios (OR) were 1.56 [95% confidence interval (95% CI), 1.22-1.99] for the <i>TERT-07 G</i>-allele, 1.27 (95% CI, 1.05-1.52) for the <i>TERT-54 T</i>-allele, and 0.79 (95% CI, 0.67-0.95) for the <i>POT1-03 A</i>-allele. <i>TERT-67</i> (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 <i>T</i>-allele. However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of <i>P</i> < 0.001 (0.05/52) except for <i>TERT-07</i>. When restricted to Caucasians (94% of the study subjects), a stronger association for the <i>TERT-07 G</i>-allele was observed with an OR of 1.60 (95% CI, 1.24-2.05; <i>P</i> = 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.</p><p><b>Conclusions:</b> Four SNPs in the <i>TERT</i> and <i>POT1</i> 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. Cancer Epidemiol Biomarkers Prev; 19(1); 219–28</p></div>