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Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival.

ABSTRACT: The impact of genetic variants in telomere pathway genes on telomere length and breast cancer survival remains unclear. We hypothesized that telomere length and genetic variants of telomere pathway genes are associated with survival among breast cancer patients. A population-based cohort study of 1,026 women diagnosed with a first primary breast cancer was conducted to examine telomere length and 52 genetic variants of 9 telomere pathway genes. Adjusted Cox regression analysis was employed to examine associations between telomere length, genetic variants and all-cause and breast cancer-specific mortality. Longer telomere length was significantly correlated with all-cause mortality in the subgroup with HER-2/neu negative tumors (HR=1.90, 95% CI: 1.12-3.22). Carrying the PINX1-33 (rs2277130) G-allele was significantly associated with increased all-cause mortality (HR=1.45, 95% CI: 1.06-1.98). Three SNPs (TERF2-03 rs35439397, TERT-14 rs2853677, and TERT-67 rs2853669) were significantly associated with reduced all-cause mortality. A similar reduced trend for breast cancer-specific mortality was observed for carrying the TERT-14 (rs2853677) T-allele (HR=0.57, 95% CI: 0.39-0.84), while carrying the POT1-18 (rs1034794) T-allele significantly increased breast cancer-specific mortality (HR=1.48, 95% CI: 1.00-2.19). However, none of the associations remained significant after correction for multiple tests. A significant dose-response effect was observed with increased number of unfavorable alleles/genotypes (PINX1-33 G-allele, POT1-18 T-allele, TERF2-03 GG, TERT-14 CC, and TERT-67 TT genotypes) and decreased survival. These data suggest that unfavorable genetic variants in telomere pathway genes may help to predict breast cancer survival.

SUBMITTER: Shen J

PROVIDER: S-EPMC3579614 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival.

Shen Jing J Gammon Marilie D MD Terry Mary Beth MB Bradshaw Patrick T PT Wang Qiao Q Teitelbaum Susan L SL Neugut Alfred I AI Santella Regina M RM

Breast cancer research and treatment 20120412 1

The impact of genetic variants in telomere pathway genes on telomere length and breast cancer survival remains unclear. We hypothesized that telomere length and genetic variants of telomere pathway genes are associated with survival among breast cancer patients. A population-based cohort study of 1,026 women diagnosed with a first primary breast cancer was conducted to examine telomere length and 52 genetic variants of 9 telomere pathway genes. Adjusted Cox regression analysis was employed to ex ...[more]

PMID: 22527105

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Project description:BackgroundTelomeres at the ends of eukaryotic chromosomes play a critical role in maintaining the integrity and stability of the genome and participate in the initiation of DNA damage/repair responses.MethodsWe performed a case-control study to evaluate the role of three SNPs (TERT-07, TERT-54 and POT1-03) in telomere maintenance genes previously found to be significantly associated with breast cancer risk. We used sister-sets obtained from the New York site of the Breast Cancer Family Registry (BCFR). Among the 313 sister-sets, there were 333 breast cancer cases and 409 unaffected sisters who were evaluated in the current study. We separately applied conditional logistic regression and generalized estimating equations (GEE) models to evaluate associations between the three SNPs and breast cancer risk within sister-sets. We examined the associations between genotype, covariates and telomere length among unaffected sisters using a GEE model.ResultsWe found no significant associations between the three SNPs in telomere maintenance genes and breast cancer risk by both conditional logistic regression and GEE models, nor were these SNPs significantly related to telomere length. Among unaffected sisters, shortened telomeres were statistically significantly correlated with never hormone replacement therapy (HRT) use. Increased duration of HRT use was significantly associated with reduced telomere length. The means of telomere length were 0.77 (SD = 0.35) for never HRT use, 0.67 (SD = 0.29) for HRT use < 5 yrs and 0.59 (SD = 0.24) for HRT use ≥ 5 yrs after adjusting for age of blood donation and race and ethnicity.ConclusionsWe found that exogenous hormonal exposure was inversely associated with telomere length. No significant associations between genetic variants and telomere length or breast cancer risk were observed. These findings provide initial evidence to understand hormonal exposure in the regulation of telomere length and breast cancer risk but need replication in prospective studies.

Dataset Information

Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival.

Publications

Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival.

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