TNF-alpha promoter polymorphisms and susceptibility to human papillomavirus 16-associated cervical cancer.
BACKGROUND
Polymorphisms in the TNF-alpha 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.


RESULTS
The association of 11 TNF-alpha single-nucleotide polymorphisms (SNPs) with susceptibility to HPV16-associated cervical cancer was investigated. Sequencing of the TNF-alpha 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-alpha SNPs and susceptibility to cervical cancer that support the involvement of the TNF- alpha promoter region in development of cervical cancer.
Deshpande
Alina
A
Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
Nolan
John P
JP
White
P Scott
PS
Valdez
Yolanda E
YE
Hunt
William C
WC
Peyton
Cheri L
CL
Wheeler
Cosette M
CM
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006630:Hispanic or Latino; D006801:Humans; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000208:ethnology / Q000235:genetics / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D044465:White People
D014409:Tumor Necrosis Factor-alpha