Publication details

Genome-wide association study of HPV seropositivity

Authors	CHEN D. MCKAY J. D. CLIFFORD Gary GABORIEAU Valerie CHABRIER Amelie WATERBOER Tim ZARIDZE David LISSOWSKA Jolanta RUDNAI Peter FABIANOVA Eleonora BENCKO Vladimir JANOUT Vladimir FORETOVÁ Lenka MATES Ioan Nicolae SZESZENIA-DABROWSKA Neonila CURADO Maria Paula KOIFMAN Sergio MENEZES Ana WUENSCH-FILHO Victor ELUF-NETO Jose GARROTE Leticia Fernandez MATOS Elena ZELENIKA Diana BOLAND Anne BOFFETTA Paolo PAWLITA Michael LATHROP Mark BRENNAN Paul
Year of publication	2011
Type	Article in Periodical
Magazine / Source	Human molecular genetics
MU Faculty or unit	Faculty of Medicine
Citation
Doi	http://dx.doi.org/10.1093/hmg/ddr383
Field	Biochemistry
Keywords	HUMAN-PAPILLOMAVIRUS TYPES; NONMELANOMA SKIN-CANCER; DISEASE ASSOCIATION; CERVICAL-CANCER; EPIDERMODYSPLASIA-VERRUCIFORMIS; UNIVERSITY-STUDENTS; HLA POLYMORPHISMS; IMMUNE-RESPONSES; HUMAN MHC; INFECTION
Description	High-risk alpha mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas beta 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 x 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 x 10(-5)), yielding P = 1.3 x 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.