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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)483-490
Number of pages8
JournalHuman Genetics
Volume121
Issue number3-4
DOIs
StatePublished - May 2007
Externally publishedYes

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Lymphotoxin-alpha
Single Nucleotide Polymorphism
Tumor Necrosis Factor-alpha
Breast Neoplasms
Genetic Promoter Regions
Alleles
Case-Control Studies
Linkage Disequilibrium
Poland
Haplotypes
Population
Communicable Diseases
Genotype
Cytokines
Inflammation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Gaudet, M. M., Egan, K. M., Lissowska, J., Newcomb, P. A., Brinton, L. A., Titus-Ernstoff, L., ... Garcia-Closas, M. (2007). Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and breast cancer risk. Human Genetics, 121(3-4), 483-490. https://doi.org/10.1007/s00439-006-0315-x

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

In: Human Genetics, Vol. 121, No. 3-4, 05.2007, p. 483-490.

Research output: Contribution to journalArticle

Gaudet, MM, Egan, KM, Lissowska, J, Newcomb, PA, Brinton, LA, Titus-Ernstoff, L, Yeager, M, Chanock, S, Welch, R, Peplonska, B, Trentham-Dietz, A & Garcia-Closas, M 2007, 'Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and breast cancer risk', Human Genetics, vol. 121, no. 3-4, pp. 483-490. https://doi.org/10.1007/s00439-006-0315-x
Gaudet MM, Egan KM, Lissowska J, Newcomb PA, Brinton LA, Titus-Ernstoff L et al. Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and breast cancer risk. Human Genetics. 2007 May;121(3-4):483-490. https://doi.org/10.1007/s00439-006-0315-x
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. / Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and breast cancer risk. In: Human Genetics. 2007 ; Vol. 121, No. 3-4. pp. 483-490.
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