Review of Mendelian Randomization Studies on Ovarian Cancer

Guo, Jian-Zeng; Xiao, Qiang; Gao, Song; Li, Xiuqin; Wu, Qi‐Jun; Gong, Ting-Ting

doi:10.3389/fonc.2021.681396

Cited by 22 publications

(18 citation statements)

References 131 publications

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“…[ 7 ] Nevertheless, observational studies can be biased by confounders and reverse causality when it comes to causal inferences. [ 8 ] The randomized controlled trial (RCT) also has its own limitations with respect to ethical concerns, time of observation, as well as resources and cost. [ 9 ] Therefore, whether there are causal associations between dietary habits and HCC risk is unclear.…”

Section: Introductionmentioning

confidence: 99%

“…[ 8 ] Most MR studies use genetic variants significantly associated with exposures as instrumental variables (IVs) to assess the associations between genetic‐predicted exposures and outcomes. [ 8 ] Owing to the fact that genetic variants are randomly inherited from parents to offspring at conception, they are less likely to be influenced by potential confounders and reverse causality. [ 8 ] A study design based on MR allows investigation of many exposures that cannot be studied RCTs.…”

Section: Introductionmentioning

confidence: 99%

“…[ 8 ] Owing to the fact that genetic variants are randomly inherited from parents to offspring at conception, they are less likely to be influenced by potential confounders and reverse causality. [ 8 ] A study design based on MR allows investigation of many exposures that cannot be studied RCTs. [ 9 ] However, to our knowledge, no MR studies have been conducted to explore the potential causal relationships between dietary habits and HCC risk.…”

Section: Introductionmentioning

confidence: 99%

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Associations between six dietary habits and risk of hepatocellular carcinoma: A Mendelian randomization study

2022

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Diet is reported to be associated with hepatocellular carcinoma (HCC), but whether there is a causal relationship remains unclear. This study aimed to explore the potential causal associations between dietary habits and HCC risk using Mendelian randomization in an East Asian population. From the BioBank Japan, we obtained summary‐level genome‐wide association studies data for the following six dietary habits: ever/never drinker (n = 165,084), alcohol consumption (n = 58,610), coffee consumption (n = 152,634), tea consumption (n = 152,653), milk consumption (n = 152,965), and yoghurt consumption (n = 152,097). We also obtained data on HCC (1866 cases and 195,745 controls). Single‐nucleotide polymorphisms (SNPs) that were associated with exposures ( p < 5 × 10 −8 ) were selected as instrumental variables (IVs). Five, two, and six SNPs were identified for ever/never drinkers, alcohol consumption, and coffee consumption. One SNP was used for consumption of tea, milk, and yoghurt. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by inverse variance weighted (for an IV with more than one SNP) or Wald ratio (for an IV with one SNP). Ever/never drinkers (OR, 1.11; 95% CI, 1.05–1.18; p < 0.001) and alcohol consumption (OR, 1.57; 95% CI, 1.32–1.86; p < 0.001) were positively associated with HCC risk. Conversely, coffee consumption was inversely related to HCC risk (OR, 0.69; 95% CI, 0.53–0.90; p = 0.007). Similar inverse associations were observed for consumption of tea, milk, and yoghurt, with ORs (95% CIs) of 0.11 (0.05–0.26), 0.18 (0.09–0.34), and 0.18 (0.09–0.34), respectively (all p < 0.001). Conclusion: There are potential causal associations between six dietary habits and HCC risk. Our findings inform clinical practice by providing evidence on the impact of dietary habits on HCC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Associations between six dietary habits and risk of hepatocellular carcinoma: A Mendelian randomization study

2022

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“…The Mendelian randomization can avoid bias from unmeasured confounding and avoid bias from reverse causation and offer some protection against biases that can be conceptualized as reverse causation ( 50 , 51 ). Our study tried to avoid some problems of confounding factors and reverse causality, but there were still some limitations.…”

Section: Discussionmentioning

confidence: 99%

The relationship between processed meat, red meat, and risk of types of cancer: A Mendelian randomization study

Liu²,

Shu³

et al. 2022

Front. Nutr.

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BackgroundObservational studies have suggested processed and red meat may increase the risk of cancer. However, the causal effects and direction between them were still unclear. We conducted two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of processed meat and red meat on the risk of nine common types of cancer, namely, lung, ovarian, endometrial, breast, kidney, gastric, prostate, skin, and oropharyngeal cancer.MethodsGenome-wide association studies (GWAS) for processed meat and red meat (pork, beef, and mutton) were obtained from the UK Biobank. GWAS of types of cancer in this study were extracted from the genetic consortia and the FinnGen consortium. The inverse variance weighted (IVW) was carried out as the main method for two-sample MR analysis. Sensitivity analyses were used to assess the robustness of the results.ResultsGenetically predicted processed meat intake was causally associated with increased risk of lung cancer (OR [odds ratio] = 1.923, 95% CI = 1.084–3.409, P = 0.025). There is no convincing evidence for the associations between genetically determined processed meat, red meat, and the risk of other cancers we studied.ConclusionOur results suggested that intake of processed meat may increase the risk of lung cancer. These findings provided no evidence to support that consumption of processed and red meat has a large effect on the risk of other cancers we studied. Further research is needed to clarify the results.

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“…The increasing use of MR (Sekula et al, 2016) has prompted both subject-specific (Pingault et al, 2016;Frayling and Stoneman, 2018;Goodarzi, 2018;Lor et al, 2019;Meng et al, 2019;Guo et al, 2021) and general reviews (Bochud and Rousson, 2010;Davies et al, 2013;Boef et al, 2015) of MR studies summarizing the state of practice of MR in the last decade. These suggest that the exclusion restriction criterion is not systematically assessed or discussed.…”

Section: Introductionmentioning

confidence: 99%

Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity

2022

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Pleiotropy assessment is critical for the validity of Mendelian randomization (MR) analyses, and its management remains a challenging task for researchers. This review examines how the authors of MR studies address bias due to pleiotropy in practice. We reviewed Pubmed, Medline, Embase and Web of Science for MR studies published before 21 May 2020 that used at least one single-nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene as instrumental variable (IV) for body mass index, irrespective of the outcome. We reviewed: 1) the approaches used to prevent pleiotropy, 2) the methods cited to detect or control the independence or the exclusion restriction assumption highlighting whether pleiotropy assessment was explicitly stated to justify the use of these methods, and 3) the discussion of findings related to pleiotropy. We included 128 studies, of which thirty-three reported one approach to prevent pleiotropy, such as the use of multiple (independent) SNPs combined in a genetic risk score as IVs. One hundred and twenty studies cited at least one method to detect or account for pleiotropy, including robust and other IV estimation methods (n = 70), methods for detection of heterogeneity between estimated causal effects across IVs (n = 72), methods to detect or account associations between IV and outcome outside thought the exposure (n = 85), and other methods (n = 5). Twenty-one studies suspected IV invalidity, of which 16 explicitly referred to pleiotropy, and six incriminating FTO SNPs. Most reviewed MR studies have cited methods to prevent or to detect or control bias due to pleiotropy. These methods are heterogeneous, their triangulation should increase the reliability of causal inference.

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Review of Mendelian Randomization Studies on Ovarian Cancer

Cited by 22 publications

References 131 publications

Associations between six dietary habits and risk of hepatocellular carcinoma: A Mendelian randomization study

Associations between six dietary habits and risk of hepatocellular carcinoma: A Mendelian randomization study

The relationship between processed meat, red meat, and risk of types of cancer: A Mendelian randomization study

Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity

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