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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Glass GV. Primary, secondary, and meta-analysis of research. Educ Res. 1976;5:3–8.
Salanti G, Sanderson S, Higgins JP. Obstacles and opportunities in meta-analysis of genetic association studies. Genet Med. 2005;7:13–20.
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.
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.
Smith GD. Mendelian randomization for strengthening causal inference in observational studies: application to gene x environment interactions. Perspect Psychol Sci. 2010;5:527–45.
Smith GD, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22.
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.
Gray R, Wheatley K. How to avoid bias when comparing bone marrow transplantation with chemotherapy. Bone Marrow Transplant. 1991;7 Suppl 3:9–12.
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.
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.
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.
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.
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.
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.
Spitz MR, Bondy ML. The evolving discipline of molecular epidemiology of cancer. Carcinogenesis. 2010;31:127–34.
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.
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.
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.
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.
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.
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.
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.
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.
Katan MB. Apolipoprotein E isoforms, serum cholesterol, and cancer. Lancet. 1986;1:507–8.
Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004;33:30–42.
VanderWeele TJ, Tchetgen Tchetgen EJ, Cornelis M, Kraft P. Methodological challenges in Mendelian randomization. Epidemiology. 2014;25:427–35.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflicts of interest
None
Rights and permissions
About this article
Cite this article
Niu, W., Gu, M. Adding Mendelian randomization to a meta-analysis—a burgeoning opportunity. Tumor Biol. 37, 1527–1529 (2016). https://doi.org/10.1007/s13277-015-4680-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-4680-8