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Genetic variation in tumor necrosis factor and lymphotoxin-alpha ( TNF–LTA) and breast cancer risk.

Authors :
Gaudet, Mia M.
Egan, Kathleen M.
Lissowska, Jolanta
Newcomb, Polly A.
Brinton, Louise A.
Titus-Ernstoff, Linda
Yeager, Meredith
Chanock, Stephen
Welch, Robert
Peplonska, Beata
Trentham-Dietz, Amy
Garcia-Closas, Montserrat
Source :
Human Genetics; Apr2007, Vol. 121 Issue 3/4, p483-490, 8p, 4 Charts
Publication Year :
2007

Abstract

Tumor necrosis factor (TNF) is critical to regulation of inflammation. Genetic variation in the promoter region of TNF has been associated with expression differences, and a range of auto-immune, infectious, and oncologic diseases. We analyzed eight common single nucleotide polymorphisms (SNPs) (rs746868, rs909253, rs1799964, rs1800630, rs1800750, rs1800629, rs361525, and rs1800610) to capture most of the genetic variation in TNF in addition to SNPs in lymphotoxin-alpha ( LTA), a pro-inflammatory cytokine in linkage disequilibrium with the TNF promoter region. SNPs were genotyped in a USA population-based case-control study (3,318 cases, 2,841 controls). Promising results were followed-up in an independent population-based case-control study in Poland (2,228 cases, 2,378 controls). In both studies, women carrying the variant allele of rs361525 were at elevated breast cancer risk compared to the GG genotype (per allele OR = 1.18, 95% CI 1.04–1.35; P for trend = 0.008). Other SNPs were not significantly associated with breast cancer risk. Haplotype analyses did not reveal any additional associations between TNF and breast cancer risk. Data from 5,269 cases and 4,982 controls suggested that the rs361525 A allele, located in the TNF promoter region, was associated with a modest increase in breast cancer risk. Additional studies are required to replicate these findings and to determine whether rs361525 is a causative SNP or is a marker of a causative SNP. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03406717
Volume :
121
Issue :
3/4
Database :
Complementary Index
Journal :
Human Genetics
Publication Type :
Academic Journal
Accession number :
24602894
Full Text :
https://doi.org/10.1007/s00439-006-0315-x