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

  • Epidemiology
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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.

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Abbreviations

95 % CI:

95 % Confidence interval

BMI:

Body mass index

ER:

Estrogen receptor

HR:

Hazard ratio

ICD:

International Classification of Diseases

LIBCSP:

Long Island Breast Cancer Study Project

PINX1 :

PIN2-interacting protein 1

POT1 :

Protection of telomeres

PR:

Progesterone receptor

Q-PCR:

Quantitative PCR

SNP:

Single nucleotide polymorphism

TERF2 :

Telomeric repeat binding factor 2

TERT :

Telomerase reverse transcriptase

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Acknowledgments

The authors acknowledge the grant support from National Cancer Institute and National Institute of Environmental Health Sciences Grants R03CA125768, U01CA/ES66572, P30ES009089, and P30ES10126; and awards from the Breast Cancer Research Foundation, and Women At Risk (WAR).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 650 West 168th Street, Black Building 1608, New York, NY, 10032, USA

    Jing Shen, Qiao Wang & Regina M. Santella

  2. Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27599, USA

    Marilie D. Gammon & Patrick T. Bradshaw

  3. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA

    Mary Beth Terry & Alfred I. Neugut

  4. Department of Community and Preventive Medicine, Mt. Sinai School of Medicine, New York, NY, 10029, USA

    Susan L. Teitelbaum

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  1. Jing Shen
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Correspondence to Jing Shen.

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Shen, J., Gammon, M.D., Terry, M.B. et al. Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival. Breast Cancer Res Treat 134, 393–400 (2012). https://doi.org/10.1007/s10549-012-2058-9

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