Skip to main content
Erschienen in: Tumor Biology 2/2016

22.12.2015 | Review

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

verfasst von: Wenquan Niu, Mingliang Gu

Erschienen in: Tumor Biology | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Glass GV. Primary, secondary, and meta-analysis of research. Educ Res. 1976;5:3–8.CrossRef Glass GV. Primary, secondary, and meta-analysis of research. Educ Res. 1976;5:3–8.CrossRef
2.
Zurück zum Zitat Salanti G, Sanderson S, Higgins JP. Obstacles and opportunities in meta-analysis of genetic association studies. Genet Med. 2005;7:13–20.CrossRefPubMed Salanti G, Sanderson S, Higgins JP. Obstacles and opportunities in meta-analysis of genetic association studies. Genet Med. 2005;7:13–20.CrossRefPubMed
3.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Smith GD, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22.CrossRefPubMed 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Spitz MR, Bondy ML. The evolving discipline of molecular epidemiology of cancer. Carcinogenesis. 2010;31:127–34.CrossRefPubMed Spitz MR, Bondy ML. The evolving discipline of molecular epidemiology of cancer. Carcinogenesis. 2010;31:127–34.CrossRefPubMed
16.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004;33:30–42.CrossRefPubMed Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004;33:30–42.CrossRefPubMed
26.
Metadaten
Titel
Adding Mendelian randomization to a meta-analysis—a burgeoning opportunity
verfasst von
Wenquan Niu
Mingliang Gu
Publikationsdatum
22.12.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4680-8

Weitere Artikel der Ausgabe 2/2016

Tumor Biology 2/2016 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.