Genetic variation in TP53 and risk of breast cancer in a population-based case-control study

Brian L. Sprague, Amy Trentham-Dietz, Montserrat Garcia-Closas, Polly A. Newcomb, Linda Titus-Ernstoff, John M. Hampton, Stephen J. Chanock, Jonathan L. Haines, Kathleen M. Egan

Research output: Contribution to journalArticle

Abstract

Whereas germ line missense mutations in the tumor suppressor gene TP53 are associated with a marked predisposition to breast cancer, single-nucleotide polymorphisms (SNPs) may play a more modest role in breast cancer susceptibility. We examined genetic variation in TP53 in relation to breast cancer risk among women aged 20-74 years in a population-based case-control study in Wisconsin, Massachusetts and New Hampshire. Analyses were conducted separately for in situ (176 cases/581 controls) and invasive (1490 cases/1291 controls) breast cancer. Oral mucosal DNA samples were genotyped for the codon 72 polymorphism in exon 4 (rs1042522), seven intronic SNPs and three SNPs residing in the 3′ untranslated region (UTR). Logistic regression was used to obtain age- and state-adjusted odds ratios for individual SNPs. Haplotypes were reconstructed using PHASE software, and the overall association with breast cancer risk was assessed using a global score test. None of the 11 individual SNPs or eight common haplotypes were significantly related to breast carcinoma in situ risk. Among all women, two linked SNPs (D′ = 0.99, r2 = 0.95) on intron 7 (rs12951053, rs12947788) were associated with modest increases in invasive breast cancer risk; however, associations were only significant for heterozygous carriers. The data suggested that additional variants in the 3′ UTR (rs9894946), and in two correlated SNPs (D′ = 0.94, r2 = 0.81) in introns 6 (rs1625895) and 4 (rs2909430), were associated with reduced invasive breast cancer risk among women aged 50 and younger only (Pinteraction

Original languageEnglish (US)
Pages (from-to)1680-1686
Number of pages7
JournalCarcinogenesis
Volume28
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

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Single Nucleotide Polymorphism
Case-Control Studies
Breast Neoplasms
Population
3' Untranslated Regions
Introns
Haplotypes
Germ-Line Mutation
Missense Mutation
Tumor Suppressor Genes
Codon
Exons
Software
Logistic Models
Odds Ratio
DNA

ASJC Scopus subject areas

  • Cancer Research

Cite this

Sprague, B. L., Trentham-Dietz, A., Garcia-Closas, M., Newcomb, P. A., Titus-Ernstoff, L., Hampton, J. M., ... Egan, K. M. (2007). Genetic variation in TP53 and risk of breast cancer in a population-based case-control study. Carcinogenesis, 28(8), 1680-1686. https://doi.org/10.1093/carcin/bgm097

Genetic variation in TP53 and risk of breast cancer in a population-based case-control study. / Sprague, Brian L.; Trentham-Dietz, Amy; Garcia-Closas, Montserrat; Newcomb, Polly A.; Titus-Ernstoff, Linda; Hampton, John M.; Chanock, Stephen J.; Haines, Jonathan L.; Egan, Kathleen M.

In: Carcinogenesis, Vol. 28, No. 8, 08.2007, p. 1680-1686.

Research output: Contribution to journalArticle

Sprague, BL, Trentham-Dietz, A, Garcia-Closas, M, Newcomb, PA, Titus-Ernstoff, L, Hampton, JM, Chanock, SJ, Haines, JL & Egan, KM 2007, 'Genetic variation in TP53 and risk of breast cancer in a population-based case-control study', Carcinogenesis, vol. 28, no. 8, pp. 1680-1686. https://doi.org/10.1093/carcin/bgm097
Sprague BL, Trentham-Dietz A, Garcia-Closas M, Newcomb PA, Titus-Ernstoff L, Hampton JM et al. Genetic variation in TP53 and risk of breast cancer in a population-based case-control study. Carcinogenesis. 2007 Aug;28(8):1680-1686. https://doi.org/10.1093/carcin/bgm097
Sprague, Brian L. ; Trentham-Dietz, Amy ; Garcia-Closas, Montserrat ; Newcomb, Polly A. ; Titus-Ernstoff, Linda ; Hampton, John M. ; Chanock, Stephen J. ; Haines, Jonathan L. ; Egan, Kathleen M. / Genetic variation in TP53 and risk of breast cancer in a population-based case-control study. In: Carcinogenesis. 2007 ; Vol. 28, No. 8. pp. 1680-1686.
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