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01.03.2008 | Epidemiology

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

verfasst von: Mia M. Gaudet, Marilie D. Gammon, Jeannette T. Bensen, Sharon K. Sagiv, Sumitra Shantakumar, Susan L. Teitelbaum, Sybil M. Eng, Alfred I. Neugut, Regina M. Santella

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2008

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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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Titel: Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York
verfasst von: Mia M. Gaudet
Marilie D. Gammon
Jeannette T. Bensen
Sharon K. Sagiv
Sumitra Shantakumar
Susan L. Teitelbaum
Sybil M. Eng
Alfred I. Neugut
Regina M. Santella
Publikationsdatum: 01.03.2008
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9573-0

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