Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

被引：155

作者：

Lesseur, Corina ^{[1
]}

Diergaarde, Brenda ^{[2
,3
]}

Olshan, Andrew F. ^{[4
,5
]}

Wunsch-Filho, Victor ^{[6
]}

Ness, Andrew R. ^{[7
,8
,9
]}

Liu, Geoffrey ^{[10
]}

Lacko, Martin ^{[11
]}

Eluf-Neto, Jose ^{[12
]}

Franceschi, Silvia ^{[1
]}

Lagiou, Pagona ^{[13
]}

Macfarlane, Gary J. ^{[14
]}

Richiardi, Lorenzo ^{[15
]}

Boccia, Stefania ^{[16
]}

Polesel, Jerry ^{[17
]}

Kjaerheim, Kristina ^{[18
]}

Zaridze, David ^{[19
]}

Johanson, Mattias ^{[1
]}

Menezes, Ana M. ^{[20
]}

Curado, Maria Paula ^{[21
]}

Robinson, Max ^{[22
]}

Ahrens, Wolfgang ^{[23
]}

Canova, Cristina ^{[24
]}

Znaor, Ariana ^{[1
,25
]}

Castellsague, Xavier ^{[26
]}

Conway, David I. ^{[27
,28
]}

Holcatova, Ivana ^{[29
]}

Mates, Dana ^{[30
]}

Vidensky, Marta ^{[31
]}

Healy, Claire M. ^{[32
]}

Szeszenia-Dbrowska, Neonila ^{[33
]}

Fabianova, Eleonora ^{[34
]}

Lissowska, Jolanta ^{[35
,36
]}

Grandis, Jennifer R. ^{[37
,38
]}

Weissler, Mark C. ^{[39
]}

Tajara, Eloiza H. ^{[40
]}

Nunes, Fabio D. ^{[41
]}

de Carvalho, Marcos B. ^{[42
]}

Thomas, Steve ^{[9
]}

Hung, Rayjean J. ^{[43
]}

Peters, Wilbert H. M. ^{[44
]}

Herrero, Rolando ^{[1
]}

Cadoni, Gabriella ^{[45
]}

Bueno-de-Mesquita, H. Bas ^{[46
,47
,48
]}

Steffen, Annika ^{[49
]}

Agudo, Antonio ^{[50
]}

Shangina, Oxana ^{[19
]}

Xiao, Xiangjun ^{[51
]}

Gaborieau, Valerie ^{[1
]}

Chabrier, Amelie ^{[1
]}

Anantharaman, Devasena ^{[1
]}

机构：

[1] Int Agcy Res Canc IARC WHO, Lyon, France

[2] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA

[3] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA

[4] Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA

[5] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[6] Univ Sao Paulo, Fac Saude Publ, Sao Paulo, Brazil

[7] Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res NIHR Biomed Res Unit Nutr Diet, Bristol, Avon, England

[8] Univ Bristol, Bristol, Avon, England

[9] Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England

[10] Princess Margaret Canc Ctr, Toronto, ON, Canada

[11] Maastricht Univ, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Maastricht, Netherlands

[12] Univ Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo, Brazil

[13] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece

[14] Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen, Scotland

[15] Univ Turin, Dept Med Sci, Turin, Italy

[16] Univ Cattolica Sacro Cuore, Fdn Policlin Agostino Gemelli, Inst Publ Hlth, Sect Hyg, Rome, Italy

[17] CRO Aviano Natl Canc Inst, Canc Epidemiol Unit, Aviano, Italy

[18] Canc Registry Norway, Oslo, Norway

[19] Russian Minist Hlth, NN Blokhin Russian Canc Res Ctr, Inst Carcinogenesis, Dept Canc Epidemiol & Prevent, Moscow, Russia

[20] Univ Fed Pelotas UFPel, Programa Posgrad Epidemiol, Pelotas, Brazil

[21] AC Camargo Canc Ctr, Int Ctr Res CIPE, Epidemiol, Sao Paulo, Brazil

[22] Newcastle Univ, Ctr Oral Hlth Res, Newcastle, England

[23] BIPS, Leibniz Inst Prevent Res & Epidemiol, Bremen, Germany

[24] Univ Padua, Dept Mol Med, Padua, Italy

[25] Croatian Natl Inst Publ Hlth, Zagreb, Croatia

[26] CIBERESP, Inst Catala Oncol, IDIBELL, Barcelona, Spain

[27] Univ Glasgow, Sch Med Dent & Nursing, Glasgow, Lanark, Scotland

[28] NHS Natl Serv Scotland NSS, Edinburgh, Midlothian, Scotland

[29] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic

[30] Natl Inst Publ Hlth, Bucharest, Romania

[31] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina

[32] Trinity Coll Dublin, Sch Dent Sci, Dublin, Ireland

[33] Nofer Inst Occupat Med, Dept Environm Epidemiol, Lodz, Poland

[34] Reg Author Publ Hlth, Banska Bystrica, Slovakia

[35] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland

[36] Inst Oncol MCMCC, Warsaw, Poland

[37] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA

[38] Univ Calif San Francisco, Clin Translat Sci Inst, San Francisco, CA 94143 USA

[39] Univ North Carolina Chapel Hill, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC USA

[40] Sch Med Sao Jose Rio Preto, Dept Mol Biol, Sao Jose Do Rio Preto, Brazil

[41] Univ Sao Paulo, Sch Dent, Dept Stomatol, Sao Paulo, Brazil

[42] Heliopolis Hosp, Dept Head & Neck Surg, Sao Paulo, Brazil

[43] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[44] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol, Nijmegen, Netherlands

[45] Univ Cattolica Sacro Cuore, Fdn Policlin Agostino Gemelli, Inst Otorhinolaryngol, Rome, Italy

[46] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants & Chron Dis DCD, Bilthoven, Netherlands

[47] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[48] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia

[49] German Inst Human Nutr Potsdam Rehbruecke DIfE, Nuthetal, Germany

[50] IDIBELL, Inst Catala Oncol, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona, Spain

来源：

NATURE GENETICS | 2016年 / 48卷 / 12期

基金：

巴西圣保罗研究基金会; 美国国家卫生研究院;

关键词：

HUMAN-PAPILLOMAVIRUS; NASOPHARYNGEAL CARCINOMA; NECK-CANCER; METAANALYSIS; HEAD; VARIANTS; GENES; PREVALENCE;

D O I：

10.1038/ng.3685

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1544 / 1550

页数：7

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