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15 March 2005

Volume 191, Number 6
The Journal of Infectious Diseases 2005;191:969–976
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19106-0020$15.00
DOI: 10.1086/427826
MAJOR ARTICLE

TNF‐α Promoter Polymorphisms and Susceptibility to Human Papillomavirus 16–Associated Cervical Cancer

Alina Deshpande,1

John P. Nolan,1,5

P. Scott White,1

Yolanda E. Valdez,1

William C. Hunt,2

Cheri L. Peyton,3 and

Cosette M. Wheeler3,4

1Bioscience Division, Los Alamos National Laboratory, Los Alamos, and 2Epidemiology and Cancer Prevention Program, and Departments of 3Molecular Genetics and Microbiology and 4Obstetrics and Gynecology, University of New Mexico Health Sciences Center, Albuquerque; 5La Jolla Bioengineering Institute, La Jolla, California

Background.Polymorphisms in the TNF‐α promoter region have recently been shown to be associated with susceptibility to cervical cancer. Some polymorphisms have been reported to influence transcription for this cytokine. Altered local levels in the cervix may influence an individual's immune response, thereby affecting persistence of human papillomavirus (HPV) 16 infection, a primary etiological factor for cervical cancer.

Methods and Results.The association of 11 TNF‐α single‐nucleotide polymorphisms (SNPs) with susceptibility to HPV16‐associated cervical cancer was investigated. Sequencing of the TNF‐α promoter region confirmed 10 SNPs, and 1 previously unreported SNP (161 bp upstream of the transcriptional start site) was discovered. Microsphere‐array flow cytometry–based genotyping was performed on 787 samples from Hispanic and non‐Hispanic white women (241 from randomly selected control subjects, 205 from HPV16‐positive control subjects, and 341 from HPV16‐positive subjects with cervical cancer). The genotype distribution of 3 SNPs (−572, −857, and −863) was significantly different between case subjects and control subjects. Analysis of haplotypes, which were computationally inferred from genotype data, also revealed statistically significant differences in haplotype distribution between case subjects and control subjects.

Conclusions.We report new associations between several TNF‐α SNPs and susceptibility to cervical cancer that support the involvement of the TNF‐α promoter region in development of cervical cancer.

Received 15 June 2004; accepted 28 September 2004; electronically published 8 February 2005.

Reprints or correspondence: Dr. John P. Nolan, La Jolla Bioengineering Institute, 505 Coast Blvd. South, La Jolla, CA 92037 ().

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  • Financial support: National Institutes of Health (grants RR01315, RR14101 [to J.P.N.], and RO1 AI/CA32917 [to C.M.W.]); United States Public Health Service (grant T32 AI07538).

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