title: Genome-wide association study of HPV seropositivity.
abstract: 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.
authors: International Agency for Research on Cancer, Lyon, France.
authors: Dan
authors: D
authors: Chen
authors: James D
authors: JD
authors: McKay
authors: Gary
authors: G
authors: Clifford
authors: Valérie
authors: V
authors: Gaborieau
authors: Amélie
authors: A
authors: Chabrier
authors: Tim
authors: T
authors: Waterboer
authors: David
authors: D
authors: Zaridze
authors: Jolanta
authors: J
authors: Lissowska
authors: Peter
authors: P
authors: Rudnai
authors: Eleonora
authors: E
authors: Fabianova
authors: Vladimir
authors: V
authors: Bencko
authors: Vladimir
authors: V
authors: Janout
authors: Lenka
authors: L
authors: Foretova
authors: Ioan Nicolae
authors: IN
authors: Mates
authors: Neonila
authors: N
authors: Szeszenia-Dabrowska
authors: Maria Paula
authors: MP
authors: Curado
authors: Sergio
authors: S
authors: Koifman
authors: Ana
authors: A
authors: Menezes
authors: Victor
authors: V
authors: Wünsch-Filho
authors: José
authors: J
authors: Eluf-Neto
authors: Leticia
authors: L
authors: Fernández Garrote
authors: Elena
authors: E
authors: Matos
authors: Diana
authors: D
authors: Zelenika
authors: Anne
authors: A
authors: Boland
authors: Paolo
authors: P
authors: Boffetta
authors: Michael
authors: M
authors: Pawlita
authors: Mark
authors: M
authors: Lathrop
authors: Paul
authors: P
authors: Brennan
mesh_terms: D055106:Genome-Wide Association Study; D015483:HIV Antibodies / Q000276:immunology; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D044465:White People / Q000235:genetics
chemical_list: D015483:HIV Antibodies