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

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

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

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,

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 (1,490 cases/1,291 controls) breast cancer. Oral mucosal DNA samples were genotyped for the codon 72 polymorphism in exon 4 (rs1,042,522), 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, r(2) = 0.95) on intron 7 (rs12,951,053, rs12,947,788) 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 (rs9,894,946), and in two correlated SNPs (D' = 0.94, r(2) = 0.81) in introns 6 (rs1,625,895) and 4 (rs2,909,430), were associated with reduced invasive breast cancer risk among women aged 50 and younger only (P(interaction) < 0.03). These results indicate that common variation in the TP53 gene could modify the risk of invasive breast cancer.

Genetic variation in TP53 and risk of breast cancer in a population-based case control study. Publishing Authors By Initials

BL Sprague,A Trentham-Dietz,M Garcia-Closas,PA Newcomb,L Titus-Ernstoff,JM Hampton,SJ Chanock,JL Haines,KM Egan,

For similar genetic phenomena: variation (genetics) research abstracts see: genetic phenomena: variation (genetics) research

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

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Carcinogenesis

VOLUME: 28

Page Numbers: 1680-6

Journal Abbreviation: Carcinogenesis

ISSN: 0143-3334

DAY: 21

MONTH: 04

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 8008055

Genetic variation in TP53 and risk of breast cancer in a population-based case control study. Keywords Mesh Terms:

KEYWORDS: Variation (Genetics)

MESH TERMS: genetics

Chemical & Substance for Abstract: Genetic variation in TP53 and risk of breast cancer in a population-based case control study. Information

Substance Name: Tumor Suppressor Protein p53

Registry Number: 0

Grant and Affiliation Information for Genetic variation in TP53 and risk of breast cancer in a population-based case control study.

AFFILIATION: Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI 53726, USA.

Country: England

AGENCY: United States NCI

GRANT: CA69664

ACRONYM: CA

MEDLINETA: Carcinogenesis

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