Journal Article

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-Neto, Leticia Fernández Garrote, Elena Matos, Diana Zelenika, Anne Boland, Paolo Boffetta, Michael Pawlita, Mark Lathrop and Paul Brennan

in Human Molecular Genetics

Volume 20, issue 23, pages 4714-4723
Published in print December 2011 | ISSN: 0964-6906
Published online September 2011 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr383
Genome-wide association study of HPV seropositivity

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High-risk α mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas β 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 as markers 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 from a 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 the minor 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=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.

Journal Article.  5575 words.  Illustrated.

Subjects: Genetics and Genomics

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