作者
Corina Lesseur,Brenda Diergaarde,Andrew F. Olshan,Victor Wünsch-Filho,Andy R Ness,Geoffrey Liu,Martin Lacko,José Eluf-Neto,Silvia Franceschi,Παγώνα Λάγιου,Gary J. Macfarlane,Lorenzo Richiardi,Stefania Boccia,Jerry Polesel,Kristina Kjærheim,Давид Заридзе,Mattias Johansson,Ana Menezes,María Paula Curado,Max Robinson,Wolfgang Ahrens,Cristina Canova,Ariana Znaor,Xavier Castellsagué,David I. Conway,Ivana Holcátová,Dana Mateş,Marta Vilensky,Claire M. Healy,Neonila Szeszenia-Dąbrowska,Eleonóra Fabiánovà,Jolanta Lissowska,Jennifer R. Grandis,Mark C. Weissler,Eloíza H. Tajara,Fábio Daumas Nunes,Marcos Brasilino de Carvalho,Steve Thomas,Rayjean J. Hung,Wilbert H. M. Peters,Rolando Herrero,Gabriella Cadoni,H. Bas Bueno-de-Mesquita,Annika Steffen,Antonio Agudo,Oxana Shangina,Xiangjun Xiao,Valérie Gaborieau,Amélie Chabrier,Devasena Anantharaman,Paolo Boffetta,Christopher I. Amos,James D. McKay
摘要
Paul Brennan and colleagues perform genome-wide association analysis for oral cavity and pharyngeal cancer in trans-ancestry populations. They find seven new loci across different cancer subtypes, including a protective association in the HLA region that has a stronger effect in patients with human papillomavirus–positive cancers. 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 × 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 × 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 × 10−6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.