Genetic Associations of 115 Polymorphisms with Cancers of the Upper Aerodigestive Tract across 10 European Countries: The ARCAGE Project

被引：74

作者：

Canova, Cristina ^{[2
]}

Hashibe, Mia ^{[1
]}

Simonato, Lorenzo ^{[2
]}

Nelis, Mari ^{[3
]}

Metspalu, Andres ^{[3
,4
]}

Lagiou, Pagona ^{[5
,6
]}

Trichopoulos, Dimitrios ^{[5
,6
]}

Ahrens, Wolfgang ^{[7
]}

Pigeot, Iris ^{[7
]}

Merletti, Franco ^{[8
,9
]}

Richiardi, Lorenzo ^{[8
,9
]}

Talamini, Renato ^{[10
]}

Barzan, Luigi ^{[11
]}

Macfarlane, Gary J. ^{[12
]}

Macfarlane, Tatiana V. ^{[12
]}

Holcatova, Ivana ^{[13
]}

Bencko, Vladimir ^{[13
]}

Benhamou, Simone ^{[14
,15
]}

Bouchardy, Christine ^{[16
]}

Kjaerheim, Kristina ^{[17
]}

Lowry, Ray ^{[18
]}

Agudo, Antonio ^{[19
]}

Castellsague, Xavier ^{[19
]}

Conway, David I. ^{[20
,21
]}

McKinney, Patricia A. ^{[21
,22
]}

Znaor, Ariana ^{[23
]}

McCartan, Bernard E. ^{[24
]}

Healy, Claire M. ^{[24
]}

Marron, Manuela ^{[1
]}

Brennan, Paul ^{[1
]}

机构：

[1] Int Agcy Res Canc, F-69008 Lyon, France

[2] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy

[3] Univ Tartu, Inst Mol & Cell Biol, Estonian Bioctr, Tartu, Estonia

[4] Univ Tartu, Estonian Genome Project, Tartu, Estonia

[5] Univ Athens, Sch Med, GR-11527 Athens, Greece

[6] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

[7] Univ Bremen, Bremen Inst Prevent Res & Social Med, Bremen, Germany

[8] Univ Turin, Turin, Italy

[9] Ctr Expt Res & Med Studies, Unit Canc Epidemiol, Turin, Italy

[10] Aviano Canc Ctr, I-33081 Aviano, Italy

[11] Gen Hosp Pordenone, Pordenone, Italy

[12] Univ Aberdeen, Sch Med, Aberdeen AB9 2ZD, Scotland

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

[14] Inst Natl Sante & Rech Med, U794, Paris, France

[15] Inst Gustave Roussy, CNRS, FRE2939, Villejuif, France

[16] Canc Registry, Geneva, Switzerland

[17] Canc Registry Norway, Oslo, Norway

[18] Univ Newcastle, Newcastle Upon Tyne, Tyne & Wear, England

[19] Inst Catala Oncol, Barcelona, Spain

[20] Univ Glasgow, Sch Dent, Glasgow, Lanark, Scotland

[21] Natl Serv Scotland, Informat Serv Div, Natl Hlth Serv, Edinburgh, Midlothian, Scotland

[22] Univ Leeds, Leeds, W Yorkshire, England

[23] Croatian Natl Inst Publ Hlth, Croatian Natl Canc Registry, Zagreb, Croatia

[24] Univ Dublin Trinity Coll, Sch Dent Sci, Dublin 2, Ireland

来源：

CANCER RESEARCH | 2009年 / 69卷 / 07期

关键词：

SQUAMOUS-CELL CARCINOMA; TUMOR-NECROSIS-FACTOR; LUNG-CANCER; ESOPHAGEAL CANCER; XENOBIOTIC METABOLISM; HEAD; RISK; NECK; TOBACCO; CARCINOGENESIS;

D O I：

10.1158/0008-5472.CAN-08-2604

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend < 0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase 1 metabolism gene, was associated with reduced UADT cancer risk (P trend = 0.01). Three SNPs in the,MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend = 0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend = 0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways. [Cancer Res 2009;69(7):2956-65]

引用

页码：2956 / 2965

页数：10

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