先前与端粒长度相关的基因对黑色素瘤风险的影响。
The effect on melanoma risk of genes previously associated with telomere length.
作者信息
Iles Mark M, Bishop D Timothy, Taylor John C, Hayward Nicholas K, Brossard Myriam, Cust Anne E, Dunning Alison M, Lee Jeffrey E, Moses Eric K, Akslen Lars A, Andresen Per A, Avril Marie-Françoise, Azizi Esther, Scarrà Giovanna Bianchi, Brown Kevin M, Dębniak Tadeusz, Elder David E, Friedman Eitan, Ghiorzo Paola, Gillanders Elizabeth M, Goldstein Alisa M, Gruis Nelleke A, Hansson Johan, Harland Mark, Helsing Per, Hočevar Marko, Höiom Veronica, Ingvar Christian, Kanetsky Peter A, Landi Maria Teresa, Lang Julie, Lathrop G Mark, Lubiński Jan, Mackie Rona M, Martin Nicholas G, Molven Anders, Montgomery Grant W, Novaković Srdjan, Olsson Håkan, Puig Susana, Puig-Butille Joan Anton, Radford-Smith Graham L, Randerson-Moor Juliette, van der Stoep Nienke, van Doorn Remco, Whiteman David C, MacGregor Stuart, Pooley Karen A, Ward Sarah V, Mann Graham J, Amos Christopher I, Pharoah Paul D P, Demenais Florence, Law Matthew H, Newton Bishop Julia A, Barrett Jennifer H
机构信息
Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, Leeds Cancer Research UK Centre, University of Leeds, Leeds, UK (MMI, DTB, JCT, MHa, JRM, JANB, JHB); Oncogenomics (NKH), Genetic Epidemiology (NGM), Inflammatory Bowel Diseases Laboratory (GLRS), Cancer Control Group (DCW), Statistical Genetics (SM, MHL), and Molecular Epidemiology (GWM), QIMR Berghofer Medical Research Institute, Brisbane, Australia; INSERM, UMR-946, Genetic Variation and Human Diseases Unit, Paris, France (MB, FD); Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France (MB, FD); Cancer Epidemiology and Services Research, Sydney School of Public Health, University of Sydney, Australia (AEC); Department of Oncology, University of Cambridge, Cambridge, UK (AMD, PDPP); Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (JEL); Centre for Genetic Origins of Health and Disease, Faculty of Medicine, Dentistry and Health Sciences, University of Western Australia, Crawley, Australia (EKM, SVW); Centre for Cancer Biomarkers CCBIO (LAA) and Gade Laboratory for Pathology (AM), Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway (LAA); Department of Pathology, Molecular Pathology (PAA) and Department of Dermatology (PH), Oslo University Hospital, Rikshospitalet, Oslo, Norway; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Dermatologie, Université Paris Descartes, Paris, France (MFA); Department of Dermatology (EA) and Oncogenics Unit (EA, EF), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv, Israel (EA); Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy (GBS, EFPG); Laboratory of Genetics of Rare Hereditary Cancers, San Martino-IST Research Hospital, Genoa, Italy (GBS, EFPG); Division of Cancer Epidemiology and Gene
出版信息
J Natl Cancer Inst. 2014 Sep 17;106(10). doi: 10.1093/jnci/dju267. Print 2014 Oct.
Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.
端粒长度与多种癌症的风险相关，但结果并不一致。在来自欧洲、以色列、美国和澳大利亚的11108例病例患者和13933例对照患者中，对先前与平均白细胞端粒长度相关的7个单核苷酸多态性（SNP）进行了基因分型或精确推算，7个SNP中的4个达到了双侧P值小于0.05。由这7个SNP得出的预测端粒长度的遗传评分与黑色素瘤风险密切相关（双侧P = 8.92×10⁻⁹）。这表明，先前观察到的端粒长度较长与黑色素瘤风险增加之间的关联并非归因于共同环境影响（如紫外线暴露）导致的混杂或反向因果关系。我们首次证明，端粒长度的多个种系遗传决定因素会影响癌症风险。
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