Journal
NATURE GENETICS
Volume 48, Issue 12, Pages 1544-1550Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3685
Keywords
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Categories
Funding
- US National Institute of Dental and Craniofacial Research (NIDCR) [1X01HG007780-0]
- International Agency for Research on Cancer
- US National Institutes of Health [P50CA097190, P30CA047904]
- National Cancer Institute [R01CA90731, U19CA148127]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [04/12054-9, 10/51168-0]
- National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme [RP-PG-0707-10034]
- Canadian Cancer Society Research Institute [020214]
- Cancer Care Ontario Research Chair
- European Commission's fifth framework programme [QLK1-2001-00182]
- Italian Association for Cancer Research
- Compagnia di San Paolo/FIRMS
- Region Piemonte
- Padova University [CPDA057222]
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 2011 10491, IG 2013 14220]
- Fondazione Veronesi
- European Commission INCO-DC programme [IC18-CT97-0222]
- Fondo para la Investigacion Cientifica y Tecnologica (Argentina)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [01/01768-2]
- European Commission's INCO-COPERNICUS Program [IC15-CT98-0332]
- US NIH/National Cancer Institute [CA92039]
- World Cancer Research Foundation [WCRF 99A28]
- Europe against Cancer [S06 96 202489 05F02]
- Fondo de Investigaciones Sanitarias, Spain [FIS 97/0024, FIS 97/0662, BAE 01/5013]
- UICC Yamagiwa-Yoshida Memorial International Cancer Study
- National Cancer Institute of Canada
- Associazione Italians per la Ricerca sul Cancro
- Pan-American Health Organization
- European Commission (DG SANCO)
- [X01HG007492-0]
- National Institute for Health Research [RP-PG-0707-10034, NF-SI-0513-10083] Funding Source: researchfish
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We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 x 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 x 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 x 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
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