Human Genetics

, Volume 121, Issue 3–4, pp 483–490

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

  • Mia M. Gaudet
  • Kathleen M. Egan
  • Jolanta Lissowska
  • Polly A. Newcomb
  • Louise A. Brinton
  • Linda Titus-Ernstoff
  • Meredith Yeager
  • Stephen Chanock
  • Robert Welch
  • Beata Peplonska
  • Amy Trentham-Dietz
  • Montserrat Garcia-Closas
Original Investigation

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.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Mia M. Gaudet
    • 1
    • 11
  • Kathleen M. Egan
    • 2
  • Jolanta Lissowska
    • 3
  • Polly A. Newcomb
    • 4
    • 5
  • Louise A. Brinton
    • 1
  • Linda Titus-Ernstoff
    • 6
    • 7
  • Meredith Yeager
    • 8
  • Stephen Chanock
    • 8
    • 9
  • Robert Welch
    • 8
  • Beata Peplonska
    • 10
  • Amy Trentham-Dietz
    • 5
  • Montserrat Garcia-Closas
    • 1
  1. 1.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human ServicesBethesdaUSA
  2. 2.Vanderbilt University Medical CenterNashvilleUSA
  3. 3.Cancer Center M. Sklodowska-Curie Institute of OncologyWarsawPoland
  4. 4.Fred Hutchinson Cancer Research CenterCancer Prevention Research GroupSeattleUSA
  5. 5.University of Wisconsin Comprehensive Cancer CenterMadisonUSA
  6. 6.Dartmouth Medical CenterLebanonUSA
  7. 7.Norris Cotton Cancer CenterLebanonUSA
  8. 8.Core Genotype Facility at the Advanced Technology CenterNational Cancer Institute, National Institutes of Health, Department of Health and Human ServicesGaithersburgUSA
  9. 9.Section on Genomic Variation, Pediatric Oncology Branch, Department of Health and Human Services, Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  10. 10.Nofer Institute of Occupational MedicineLodzPoland
  11. 11.National Cancer InstituteRockvilleUSA

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