Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 2/2016

01-02-2016 | Review

Adding Mendelian randomization to a meta-analysis—a burgeoning opportunity

Authors: Wenquan Niu, Mingliang Gu

Published in: Tumor Biology | Issue 2/2016

Login to get access

Abstract

Current literature is teeming with tens of thousands of meta-analyses, but only a small fraction made seminal contributions to enriching our understanding of the mechanisms of carcinogenesis, possibly due to chance, bias, confounding, or reverse causality. The incorporation of Mendelian randomization (MR) with a meta-analysis has revolutionized traditional practice and is emerging as a viable technique to strengthen causal unconfounded inferences from observational data. We therefore highlight the importance of integrated MR meta-analysis in cancer epidemiology and provide an overview of three existing instrumental selection strategies in medical literature.
Literature
1.
Glass GV. Primary, secondary, and meta-analysis of research. Educ Res. 1976;5:3–8.CrossRef
2.
Salanti G, Sanderson S, Higgins JP. Obstacles and opportunities in meta-analysis of genetic association studies. Genet Med. 2005;7:13–20.CrossRefPubMed
3.
Thompson JR, Minelli C, Abrams KR, Tobin MD, Riley RD. Meta-analysis of genetic studies using Mendelian randomization—a multivariate approach. Stat Med. 2005;24:2241–54.CrossRefPubMed
4.
Proitsi P, Lupton MK, Velayudhan L, Newhouse S, Fogh I, Tsolaki M, et al. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis. PLoS Med. 2014;11:e1001713.CrossRefPubMedPubMedCentral
5.
Smith GD. Mendelian randomization for strengthening causal inference in observational studies: application to gene x environment interactions. Perspect Psychol Sci. 2010;5:527–45.CrossRefPubMed
6.
Smith GD, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22.CrossRefPubMed
7.
Minelli C, Thompson JR, Tobin MD, Abrams KR. An integrated approach to the meta-analysis of genetic association studies using Mendelian randomization. Am J Epidemiol. 2004;160:445–52.CrossRefPubMed
8.
Gray R, Wheatley K. How to avoid bias when comparing bone marrow transplantation with chemotherapy. Bone Marrow Transplant. 1991;7 Suppl 3:9–12.PubMed
9.
Kivimaki M, Lawlor DA, Eklund C, Smith GD, Hurme M, Lehtimaki T, et al. Mendelian randomization suggests no causal association between C-reactive protein and carotid intima-media thickness in the young Finns study. Arterioscler Thromb Vasc Biol. 2007;27:978–9.CrossRefPubMed
10.
Boccia S, Hashibe M, Galli P, De Feo E, Asakage T, Hashimoto T, et al. Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach. Cancer Epidemiol Biomarkers Prev. 2009;18:248–54.CrossRefPubMed
11.
Lewis SJ, Smith GD. Alcohol, ALDH2, and esophageal cancer: a meta-analysis which illustrates the potentials and limitations of a Mendelian randomization approach. Cancer Epidemiol Biomarkers Prev. 2005;14:1967–71.CrossRefPubMed
12.
Pei Y, Xu Y, Niu W. Causal relevance of circulating adiponectin with cancer: a meta-analysis implementing Mendelian randomization. Tumour Biol. 2014;36(2):585–94.CrossRefPubMed
13.
Allin KH, Nordestgaard BG, Zacho J, Tybjaerg-Hansen A, Bojesen SE. C-reactive protein and the risk of cancer: a Mendelian randomization study. J Natl Cancer Inst. 2010;102:202–6.CrossRefPubMed
14.
Wu X, Gu J, Grossman HB, Amos CI, Etzel C, Huang M, et al. Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet. 2006;78:464–79.CrossRefPubMedPubMedCentral
15.
Spitz MR, Bondy ML. The evolving discipline of molecular epidemiology of cancer. Carcinogenesis. 2010;31:127–34.CrossRefPubMed
16.
Meng QH, Xu E, Hildebrandt MA, Liang D, Lu K, Ye Y, et al. Genetic variants in the fibroblast growth factor pathway as potential markers of ovarian cancer risk, therapeutic response, and clinical outcome. Clin Chem. 2014;60:222–32.CrossRefPubMed
17.
Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, et al. Complement factor h polymorphism in age-related macular degeneration. Science. 2005;308:385–9.CrossRefPubMedPubMedCentral
18.
McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9:356–69.CrossRefPubMed
19.
Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet. 2012;380:572–80.CrossRefPubMedPubMedCentral
20.
Holmes MV, Asselbergs FW, Palmer TM, Drenos F, Lanktree MB, Nelson CP, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 2014.
21.
Bonilla C, Gilbert R, Kemp JP, Timpson NJ, Evans DM, Donovan JL, et al. Using genetic proxies for lifecourse sun exposure to assess the causal relationship of sun exposure with circulating vitamin d and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2013;22:597–606.CrossRefPubMedPubMedCentral
22.
Thrift AP, Shaheen NJ, Gammon MD, Bernstein L, Reid BJ, Onstad L, et al. Obesity and risk of esophageal adenocarcinoma and Barrett’s esophagus: a Mendelian randomization study. J Natl Cancer Inst. 2014;106.
23.
Conrad DF, Jakobsson M, Coop G, Wen X, Wall JD, Rosenberg NA, et al. A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nat Genet. 2006;38:1251–60.CrossRefPubMed
24.
25.
Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004;33:30–42.CrossRefPubMed
26.
Metadata
Title
Adding Mendelian randomization to a meta-analysis—a burgeoning opportunity
Authors
Wenquan Niu
Mingliang Gu
Publication date
01-02-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4680-8

Other articles of this Issue 2/2016

Tumor Biology 2/2016 Go to the issue

Original Article

Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival

Original Article

RETRACTED ARTICLE: Targeted DNA methylation analysis explores association of adenocarcinoma and neuroendocrine epitypes with lung cancer

Original Article

Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression

Original Article

Propensity score-based comparison of hepatic resection and transarterial chemoembolization for patients with advanced hepatocellular carcinoma

Original Article

Gambogic acid enhances the radiosensitivity of human esophageal cancer cells by inducing reactive oxygen species via targeting Akt/mTOR pathway

Original Article

Long non-coding RNA MALAT1 modulates radiosensitivity of HR-HPV+ cervical cancer via sponging miR-145
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits