Figueroa Jonine D, Han Summer S, Garcia-Closas Montserrat, Baris Dalsu, Jacobs Eric J, Kogevinas Manolis, Schwenn Molly, Malats Nuria, Johnson Alison, Purdue Mark P, Caporaso Neil, Landi Maria Teresa, Prokunina-Olsson Ludmila, Wang Zhaoming, Hutchinson Amy, Burdette Laurie, Wheeler William, Vineis Paolo, Siddiq Afshan, Cortessis Victoria K, Kooperberg Charles, Cussenot Olivier, Benhamou Simone, Prescott Jennifer, Porru Stefano, Bueno-de-Mesquita H Bas, Trichopoulos Dimitrios, Ljungberg Börje, Clavel-Chapelon Françoise, Weiderpass Elisabete, Krogh Vittorio, Dorronsoro Miren, Travis Ruth, Tjønneland Anne, Brenan Paul, Chang-Claude Jenny, Riboli Elio, Conti David, Gago-Dominguez Manuela, Stern Mariana C, Pike Malcolm C, Van Den Berg David, Yuan Jian-Min, Hohensee Chancellor, Rodabough Rebecca, Cancel-Tassin Geraldine, Roupret Morgan, Comperat Eva, Chen Constance, De Vivo Immaculata, Giovannucci Edward, Hunter David J, Kraft Peter, Lindstrom Sara, Carta Angela, Pavanello Sofia, Arici Cecilia, Mastrangelo Giuseppe, Karagas Margaret R, Schned Alan, Armenti Karla R, Hosain G M Monawar, Haiman Chris A, Fraumeni Joseph F, Chanock Stephen J, Chatterjee Nilanjan, Rothman Nathaniel, Silverman Debra T
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, Institute for Cancer Research, London, UK, Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, Municipal Institute of Medical Research, Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, National School of Public Health, Athens, Greece, Maine Cancer Registry, Augusta, ME, USA, Spanish National Cancer Research Centre (CNIO), Madrid, Spain, Vermont Cancer Registry, Burlington, VT, USA, Center for Genomics Research, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD, USA, Information Management Services, Inc., Rockville, MD, USA, Imperial College London, London, UK, Department of Preventive Medicine and Department of Obstetrics & Gynecology, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA, Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA, USA, Department of Urology, Assistance Publique-Hôpitaux de Paris, Tenon Hospital, Paris, France, Centre de Recherche sur les Pathologies Prostatiques, Paris, France, Institut national de la sante et de la recherche medicale, U946, Foundation Jean Dausset Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France, Centre National de la Receherche Scientifique, UMR8200, Institut Gustave-Roussy, Villejuif, France, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy, National Institute for Public Health and the Environment (RIVM), Biltho
Institute for Cancer Research, London, UK.
Carcinogenesis. 2014 Aug;35(8):1737-44. doi: 10.1093/carcin/bgu064. Epub 2014 Mar 24.
Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10(-) (5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 × 10(-) (7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 × 10(-) (7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
膀胱癌是一种具有已知环境和遗传风险因素的复杂疾病。我们基于美国国立癌症研究所膀胱癌全基因组关联研究（GWAS）中3002例病例和4411例对照的初筛数据，开展了一项关于吸烟与膀胱癌风险的全基因组相互作用研究（GWAS）。采用替代方法评估个体单核苷酸多态性（SNP）与吸烟暴露之间的加性和乘性相互作用。相互作用P值<5×10⁻⁵的SNP在一个包含2422例膀胱癌病例和5751例对照的独立数据集中进一步评估。我们鉴定出10个SNP，它们在初始数据集和合并数据集中均以一致的方式显示出关联性，为与烟草使用的相互作用提供了证据。此外，这些新SNP中的两个在烟草使用亚组中显示出与膀胱癌关联的强有力证据，接近全基因组显著性水平。具体而言，位于6p25.3的rs1711973（FOXF2）是从不吸烟者的易感性SNP [合并比值比（OR）=1.34，95%置信区间（CI）=1.20 - 1.50，P值=5.18×10⁻⁷]；位于6q25.3的rs12216499（RSPH3 - TAGAP - EZR）是曾经吸烟者的易感性SNP（合并OR = 0.75，95% CI = 0.67 - 0.84，P值=6.35×10⁻⁷）。在我们对吸烟与膀胱癌的分析中，乘性相互作用检验似乎更常识别出从不吸烟者中具有关联性的易感位点，而加性相互作用分析识别出吸烟者中更多具有关联性的位点——包括已知的吸烟与NAT2乙酰化相互作用。我们的研究结果为烟草与膀胱癌的基因 - 环境相互作用提供了更多证据。
