Variation in HLA Class I Antigen-Processing Genes and Susceptibility to Human Papillomavirus Type 16—Associated Cervical Cancer

• Published in: The Journal of infectious diseases Vol. 197; no. 3; pp. 371 - 381
• Main Authors: Deshpande, Alina, Wheeler, Cosette M., Hunt, William C., Peyton, Cheri L., White, P. Scott, Valdez, Yolanda E., Nolan, John P.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.02.2008; University of Chicago Press
• Subjects: Alleles; ATP-Binding Cassette Sub-Family B Member 2; ATP-Binding Cassette Transporters - chemistry; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette, Sub-Family B, Member 3; Biological and medical sciences; Case-Control Studies; Cervical cancer; Codons; Cysteine Endopeptidases - genetics; Exons; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetic Variation; Genotypes; Haplotypes; Hispanics; Histocompatibility Antigens Class I - genetics; HLA antigens; Human papillomavirus 16; Human papillomavirus 16 - genetics; Humans; Introns; Medical sciences; Membrane Transport Proteins - genetics; Microbiology; Miscellaneous; Multienzyme Complexes - genetics; Papillomavirus Infections - genetics; Polymerase chain reaction; Polymorphism, Single Nucleotide; Proteasome Endopeptidase Complex; Protein Conformation; Reference Values; Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - virology; Virology; Viruses; Papillomavirus; Virus; Human papillomavirus 16; Human papillomavirus; Papovaviridae; Malignant tumor; Uterine cervix diseases; Class I histocompatibility antigen; Cervical cancer; Cancer; Female genital diseases
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/524300

Background. Persistent infection with human papillomavirus type 16 (HPV16) is a primary etiological factor for the development of cervical cancer. Genes involved in antigen processing influence both the repertoire of antigens presented by HPV16-infected cells and the nature of HPV16-specific immune responses. Genetic variation in these genes may affect protein structure and function and, consequently, the ability of an individual to clear HPV infection. Methods. Thirty-five single-nucleotide polymorphisms (SNPs) in 5 genes (LMP2, TAP1, LMP7, TAP2, and Tapasin) were investigated for association with susceptibility to HPV16-associated cervical cancer. Sequencing of these genes resulted in the discovery of 15 previously unreported SNPs. Microsphere-array flow cytometry—based genotyping was conducted on 787 samples from Hispanic and non-Hispanic white women (241 randomly selected control subjects, 205 HPV16-positive control subjects, and 341 HPV16-positive case subjects with cervical cancer). Results. For 9 SNPs, 8 of which had not previously been reported in the context of cervical cancer, there were statistically significant differences between the genotype distribution in case subjects and that in control subjects. Haplotype analysis of 3 haplotype blocks revealed 3 haplotypes with significant differences in frequency in case-control comparisons. Both HPV16-specific and non—type-specific differences in genotype distribution were seen. Conclusions. Genes involved in antigen processing for HLA class I presentation may contribute to susceptibility to cervical cancer.