Genome-wide association study of HPV seropositivity

Dan Chen, James D. McKay, Gary Clifford, Valérie Gaborieau, Amélie Chabrier, Tim Waterboer, David Zaridze, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Vladimir Bencko, Vladimir Janout, Lenka Foretova, Ioan Nicolae Mates, Neonila Szeszenia-Dabrowska, Maria Paula Curado, Sergio Koifman, Ana Menezes, Victor Wünsch-Filho, José Eluf-NetoLeticia Fernández Garrote, Elena Matos, Diana Zelenika, Anne Boland, Paolo Boffetta, Michael Pawlita, Mark Lathrop, Paul Brennan

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Abstract

High-risk α mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers,whereas b cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer. Although antibodies against the capsid protein L1 of HPV are considered asmarkers of cumulative exposure, not all infected persons seroconvert. To identify common genetic variants that influence HPV seroconversion,we performed a two-stage genome-wide association study. Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out using the Illumina HumanHap300 BeadChip in 4811 subjects froma central European case-control study of lung, head and neck and kidney cancer that had serology data available on 13 HPV types. Only one association met genome-wide significance criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.24-1.50 for theminor allele G; P = 1.2 × 10 -10], a common genetic variant (minor allele frequency = 0.33) located within the major histocompatibility complex (MHC) II region at 6p21.32. This association was subsequently replicated in an independent set of 2344 subjects from a Latin American case-control study of head and neck cancer (OR = 1.35, 95% CI = 1.18-1.56, P = 2.2 × 10 -5), yielding P = 1.3 × 10 -14 in the combined analysis (P-heterogeneity 5 0.87). No heterogeneity was noted by cancer status(controls/lung cancer cases/head and neck cancer cases/kidney cancer cases). This study provides a proof of principle that genetic variation plays a role in antibody reactivity to HPV infection.

Original languageEnglish
Article numberddr383
Pages (from-to)4714-4723
Number of pages10
JournalHuman molecular genetics
Volume20
Issue number23
DOIs
Publication statusPublished - Dec 1 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Chen, D., McKay, J. D., Clifford, G., Gaborieau, V., Chabrier, A., Waterboer, T., Zaridze, D., Lissowska, J., Rudnai, P., Fabianova, E., Bencko, V., Janout, V., Foretova, L., Mates, I. N., Szeszenia-Dabrowska, N., Curado, M. P., Koifman, S., Menezes, A., Wünsch-Filho, V., ... Brennan, P. (2011). Genome-wide association study of HPV seropositivity. Human molecular genetics, 20(23), 4714-4723. [ddr383]. https://doi.org/10.1093/hmg/ddr383