Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia

被引：32

作者：

Gu, Fangyi ^{[1
,2
]}

Zhang, Han ^{[1
]}

Hyland, Paula L. ^{[1
]}

Berndt, Sonja ^{[1
]}

Gapstur, Susan M. ^{[3
]}

Wheeler, William ^{[4
]}

Amos, Christopher I. ^{[5
]}

Bezieau, Stephane ^{[6
]}

Bickeboller, Heike ^{[7
]}

Brenner, Hermann ^{[8
,9
,10
,11
]}

Brennan, Paul ^{[12
]}

Chang-Claude, Jenny ^{[13
]}

Conti, David V. ^{[14
]}

Doherty, Jennifer Anne ^{[15
]}

Gruber, Stephen B. ^{[14
]}

Harrison, Tabitha A. ^{[16
]}

Hayes, Richard B. ^{[17
]}

Hoffmeister, Michael ^{[8
]}

Houlston, Richard S. ^{[18
]}

Hung, Rayjean J. ^{[19
]}

Jenkins, Mark A. ^{[20
]}

Kraft, Peter ^{[21
]}

Lawrenson, Kate ^{[22
]}

Mckay, James ^{[12
]}

Markt, Sarah ^{[21
]}

Mucci, Lorelei ^{[21
]}

Phelan, Catherine M. ^{[23
]}

Qu, Conghui ^{[16
]}

Risch, Angela ^{[24
,25
,26
,27
,28
]}

Rossing, Mary Anne ^{[16
]}

Wichmann, H. -Erich ^{[29
,30
,31
]}

Shi, Jianxin ^{[1
]}

Schernhammer, Eva ^{[21
,32
,33
]}

Yu, Kai ^{[1
]}

Landi, Maria Teresa ^{[1
]}

Caporaso, Neil E. ^{[1
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[2] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[3] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[4] Informat Management Serv Inc, Rockville, MD USA

[5] Geisel Dartmouth Med Sch, Lebanon, NH USA

[6] CHU Nantes, Serv Gertet Med, Nantes, France

[7] Univ Med Ctr Gottingen, Dept Genet Epidemiol, Gottingen, Germany

[8] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[9] Natl Ctr Tumor Dis NCI, Div Prevent Oncol, Heidelberg, Germany

[10] German Canc Res Ctr, Heidelberg, Germany

[11] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[12] Int Agcy Res Canc, Lyon, France

[13] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[14] Univ South Calif, Keck Sch Med, Los Angeles, CA USA

[15] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA

[16] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[17] NYU, Sch Med, Dept Popubat Hlth, New York, NY USA

[18] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England

[19] Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[20] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Parkville, Vic, Australia

[21] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[22] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[23] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Dept Canc Epidemiol, Tampa, FL USA

[24] Univ Salzburg, Div Mol Biol, Salzburg, Austria

[25] Canc Cluster Sarzburg, Salzburg, Austria

[26] Translat Lung Res Ctr, Heidelberg, Germany

[27] German Ctr Lung Res DZL, Giessen, Germany

[28] DKFZ German Canc Res Ctr, Div Epigen & Canc Risk Factors, Leidelberg, Germany

[29] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Bavaria, Germany

[30] Helmholtz Ctr Munich, Inst Epidemiol 2, Neuherberg, Germany

[31] Tech Univ Munich, Inst Med Stat & Epidemiol, Munich, Germany

[32] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA

[33] Med Univ Vienna, Dept Epidemiol, Vienna, Austria

来源：

INTERNATIONAL JOURNAL OF CANCER | 2017年 / 141卷 / 09期

基金：

瑞典研究理事会; 美国国家卫生研究院; 英国医学研究理事会; 加拿大健康研究院;

关键词：

circadian rhythm; melatonin; prostate cancer; cancer; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; DNA-DAMAGE; SHIFT-WORK; CELL-PROLIFERATION; COLORECTAL-CANCER; LUNG-CANCER; NIGHT WORK; CLOCK; MELATONIN;

D O I：

10.1002/ijc.30883

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene-based and pathway-based analyses by applying the summary-based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction (rho(pathway) < 0.00625). The two most significant genes were NPAS2 (rho(gene) = 0.0062) and AANAT (rho(gene) = 0.00078); the latter being significant after Bonferroni correction. For colorectal cancer, we observed a suggestive association with the circadian rhythm pathway in GAME-ON (peat,way = 0.021); this association was not confirmed in GECCO (rho(pathway) = 0.76) or the combined data In (rho(pathway) = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms.

引用

页码：1794 / 1802

页数：9

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