Format

Send to

Choose Destination
Cancer Med. 2016 Jun;5(6):1125-36. doi: 10.1002/cam4.695. Epub 2016 Mar 19.

Blood lipids and prostate cancer: a Mendelian randomization analysis.

Author information

1
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
2
MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
3
Integrative Cancer Epidemiology Programme, University of Bristol, Bristol, United Kingdom.
4
IGFs and Metabolic Endocrinology Group, School of Clinical Sciences North Bristol, University of Bristol, Bristol, BS10 5NB, United Kingdom.
5
Department of Medicine, Division of Endocrinology, Epidemiology, Biostatistics and Occupational Health McGill University, Montreal, Quebec, Canada.
6
Department of Twin Research, King's College London, London, SE1 7EH, United Kingdom.
7
The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
8
The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, United Kingdom.
9
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge, United Kingdom.
10
Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom.
11
Institute of Population Health, University of Manchester, Manchester, M13 9PL, United Kingdom.
12
Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria, Australia.
13
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
14
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
15
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
16
Department of Medical Biochemistry and Genetics, University of Turku and Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, Turku, Finland.
17
Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.
18
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev, DK-2730, Denmark.
19
Cancer Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
20
Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke's Hospital, Box 279, Hills Road, Cambridge, United Kingdom.
21
Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
22
Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom.
23
Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR, United Kingdom.
24
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
25
Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
26
International Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville, 20850, Maryland.
27
Mayo Clinic, Rochester, Minnesota.
28
Department of Urology, University Hospital, Ulm, Germany.
29
Institute of Human Genetics University Hospital, Ulm, Germany.
30
Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street- ASB II-3, Boston, Massachusetts, 02115.
31
Washington University, St. Louis, Missouri.
32
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
33
Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
34
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
35
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
36
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
37
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, Magnolia Dr., Tampa, Florida, 12902.
38
Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.
39
Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
40
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
41
Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
42
The University of Surrey, Surrey, GU2 7XH, United Kingdom.
43
National Institute for Health Research, Bristol Nutrition Biomedical Research Unit, Bristol, United Kingdom.

Abstract

Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy.

KEYWORDS:

Cholesterol; Mendelian randomization; prostate cancer; statins

PMID:
26992435
PMCID:
PMC4924371
DOI:
10.1002/cam4.695
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center