Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 141, Issue 9, Pages 1794-1802Publisher
WILEY
DOI: 10.1002/ijc.30883
Keywords
circadian rhythm; melatonin; prostate cancer; cancer
Categories
Funding
- National Institute of Health [U19 CA148127-01, 1U19CA148127-02, U19 CA148065, U19 CA148107, R01 CA81488, P30 CA014089]
- Canadian Cancer Society Research institute [020214]
- GAME-ON U19 initiative for prostate cancer [U19 CA148537]
- National Cancer Institute, National Institutes of Health, US Department of Health and Human Services [U01 CA137088, R01 CA059045]
- Regional Council of Pays de la Loire
- Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC)
- Association Anne de Bretagne Genetique
- Liguc Regionale Centre le Cancer [(LRCC)
- ASTERISK: a Hospital Clinical Research Program (PHRC)]
- German Research Council [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]
- German Federal Ministry of Education and Research [01KH0404, 01ER0814]
- Ontario Research Fund
- Canadian Institutes of Health Research
- Ontario Institute for Cancer Research through Ontario Ministry of Research and Innovation
- National Cancer Institute [NIH, Division of Cancer Prevention, DHHS (PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics)]
- National Institutes of Health (NIH)
- Genes, Environment, and Health Initiative [GEI (Lung Cancer and Smoking study)] [Z01 CP 010200, NIH U01 HG004446, NIH GEI U01 HG 004438]
- GENEVA Coordinating Center
- Johns Hopkins University Center for Inherited Disease Research conducted genotyping (For the lung study)
- National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, FIHSN268201100002C, HESN268201100003C, HHSN268201100004C, HHSN271201100004C]
- Swedish Cancer Foundation [09-0677, 11-484, 12-823]
- Cancer Risk Prediction Center (CRisP)
- Linneus Centre [70867902]
- Swedish Research Council [K2010-70X-20430-04-3, 2014-2269]
- Canadian Institutes of Health Research (European Commission's Seventh Framework Programme grant agreement
- CRUK GWAS) [223175 (HEALTH-F2-2009-223175)]
- Cancer Research UK [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135]
- National Institute of Health (NIH
- Cancer Post-Cancer GWAS initiative grant) [1 U19 CA 148537-01]
- Institute of Cancer Research and The Everyman Campaign
- Prostate Cancer Research Foundation
- Prostate Action
- Orchid Cancer Appeal
- National Cancer Research Network UK
- National Cancer Research Institute (NCRI) UK
- NIHR (NIHR Biomedical Research Centre at The Institute of Cancer Research)
- NIHR (Royal Marsden NHS Foundation Trust)
- National Health and Medical Research Council, Australia (The Prostate Cancer Program of Cancer Council Victoria) [126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394, 614296]
- VicHealth
- Cancer Council Victoria
- Prostate Cancer Foundation of Australia
- Whitten Foundation
- PricewaterhouseCoopers
- Tattersall's
- National Human Genome Research Institute
- The National Institute of Health [U19 CA148112-01, R01-CA149429, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, P50 CA 127003, R01 CA137178, P01 CA 087969, R01 CA151993, R01 CA042182, U01 CA074783, R01 CA076366, K05 CA154337]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available