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Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

p53 participates in cell cycle control, programmed cell death/apoptosis, and DNA repair, all pathways involved in carcinogenesis. TP53 variants may influence p53 function.

Objectives

We evaluated whether three well-characterized TP53 variants—Ex4 + 119 C > G (rs#1042522, Arg72Pro), IVS6 + 62 A > G (rs#1625895), and an IVS3 16 bp insertion/ deletion (INDEL; rs#17878362)—were associated with breast cancer risk in a population-based case-control study.

Methods

Genotypes and haplotypes were determined using long-range PCR in a sample of 578 cases and 390 controls.

Results

For the Ex4 + 19 C > G SNP (rs1042522), women with the heterozygous genotype (G/C) had a 32% increase in breast cancer risk. Other variants were not associated with risk. We further examined whether these associations were modified by cigarette smoking status and detection of PAH–DNA adducts in circulating lymphocytes. Among current smokers, each copy of the minor alleles for the IVS6 + 62 A > G SNP (rs1625895) and the IVS3 INDEL polymorphism (rs17878362) was associated with lower breast cancer risk (OR = 0.49, 95% CI 0.27–0.90; OR = 0.42, 95% CI 0.22–0.78, respectively). However, among former smokers, the homozygous variant genotype for these 2 SNPs was observed among cases (4.1 and 3.2%, respectively) and not controls. Genotype associations were not modified by the presence or absence of DNA adducts in circulating lymphocytes. Three-loci haplotypes were not significantly associated with breast cancer risk.

Conclusions

These results should be confirmed in larger studies, but suggest that cigarette smoking may influence breast cancer risk through interaction with p53.

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Abbreviations

OR:

Odds ratio

CI:

Confidence interval

PAH:

Polycyclic aromatic hydrocarbons

INDEL:

Insertion/deletion

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Acknowledgements

For their valuable contributions, the authors thank: members of the Long Island Breast Cancer Network; the participating institutions; our NIH and NIEHS collaborators; members of the External Advisory Committee to the population-based case-control study. This work was supported by grants from NCI/NIEHS (UO1CA/ES66572) and NIEHS (P30ES10126 and P30ES09089), and resources from the NIOSH intramural program.

Author information

Author notes

  1. Sharon K. Sagiv

    Present address: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA

  2. Sumitra Shantakumar

    Present address: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA

Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA

    Mia M. Gaudet, Marilie D. Gammon, Jeannette T. Bensen, Sharon K. Sagiv & Sumitra Shantakumar

  2. Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY, USA

    Susan L. Teitelbaum

  3. Global Epidemiology, Pfizer, Inc., New York, NY, USA

    Sybil M. Eng

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

    Alfred I. Neugut

  5. Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Alfred I. Neugut

  6. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA

    Regina M. Santella

  7. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Bethesda, MD, 20852, USA

    Mia M. Gaudet

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  1. Mia M. Gaudet
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Corresponding author

Correspondence to Mia M. Gaudet.

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Gaudet, M.M., Gammon, M.D., Bensen, J.T. et al. Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York. Breast Cancer Res Treat 108, 93–99 (2008). https://doi.org/10.1007/s10549-007-9573-0

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  • DOI: https://doi.org/10.1007/s10549-007-9573-0

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