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Gene-Environment Interactions Between PPARG2 Variant and Lifestyle Factors in Relation to Cancer RIsk: A Systematic Review

ABSTRACT: Abstract Objectives A genetic variant in peroxisome proliferator-activated receptor-gamma (PPARG2 Pro12Ala; rs1801282) has been linked to both carcinogenesis and lifestyle factors such as energy balance and fat intake and identified as modifiers of risk in several different cancers. However, to date, no systematic review has been conducted. We conducted a systematic literature review to summarize the current evidence on whether associations between lifestyle factors and risk of cancer are modified by the PPARG2 Pro12Ala variant. Methods We conducted a systematic literature review of studies published before July 2019 using the PubMed database. We included observational studies that: 1) included diet, anthropometrics and physical activity as lifestyle factors; 2) had the risk of incident cancer in any site as an outcome; 3) included controls (participants free of cancer); and 4) reported a statistical significance of interaction effects between the PPARG2 variant and lifestyle factors. Results After applying the inclusion criteria to 3424 identified abstracts, 14 studies of cancers in colon/rectum (n = 6), breast (n = 3), prostate (n = 3), pancreas (n = 1) and endometrium (n = 1) were selected, which included a total of 22,267 participants with 9290 cancer cases. Alcohol consumption had a statistically significant interaction with the PPARG2 variant in all three studies of colorectal and breast cancers investigating this interaction. Dietary factors such as fried food intake, refined grain intake, dietary vitamin A intake, lutein intake and Prudent dietary pattern significantly interacted with the PPARG2 variant, whereas other dietary factors such as dietary fat and meat intakes did not. Body mass index, waist-to-hip ratio and physical activity level did not significantly interact with the PPARG2 variant in all six studies of colorectal, breast, prostate, pancreatic and endometrial cancers, except for one study on body mass index and prostate cancer. Conclusions Our systematic review shows statistically significant, although inconsistent, interactions between PPARG2 Pro12Ala variant and lifestyle factors on cancer risk. This suggests that lifestyle recommendations for cancer prevention may need to be tailored based on genetic factors such as PPARG2 Pro12Ala variant. Funding Sources This study was funded by the OHSU/OSU Cancer Prevention and Control Initiative.

SUBMITTER: Tran L

PROVIDER: S-EPMC7258078 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Project description:BackgroundAmong candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association Studies. We aimed to conduct a systematic review of the literature on the modification effect of TCF7L2 on the relation between glycemic parameters and lifestyle factors.MethodsA systematic literature search was done for relevant publications using electronic databases, including PubMed, EMBASE, Scopus, and Web of Science, from January 1, 2000, to November 2, 2021.ResultsThirty-eight studies (16 observational studies, six meal test trials, and 16 randomized controlled trials (RCTs)) were included. Most observational studies had been conducted on participants with non-diabetes showing that TCF7L2 modified the association between diet (fatty acids and fiber) and insulin resistance. In addition, findings from meal test trials showed that, compared to non-risk-allele carriers, consumption of meals with different percentages of total dietary fat in healthy risk-allele carriers increased glucose concentrations and impaired insulin sensitivity. However, ten RCTs, with intervention periods of less than ten weeks and more than one year, showed that TCF7L2 did not modify glycemic parameters in response to a dietary intervention involving different macronutrients. However, two weight loss dietary RCTs with more than 1-year duration showed that serum glucose and insulin levels decreased and insulin resistance improved in non-risk allele subjects with overweight/obesity. Regarding artichoke extract supplementation (ALE), two RCTs observed that ALE supplementation significantly decreased insulin concentration and improved insulin resistance in the TT genotype of the rs7903146 variant of TCF7L2. In addition, four studies suggested that physical activity levels and smoking status modified the association between TCF7L2 and glycemic parameters. However, three studies observed no effect of TCF7L2 on glycemic parameters in participants with different levels of physical activity and smoking status.ConclusionThe modification effects of TCF7L2 on the relation between the lifestyle factors (diet, physical activity, and smoking status) and glycemic parameters were contradictory.Prospero registration numberCRD42020196327.

Project description:BackgroundThe abuse of psychogenic drugs can lead to multiple health-related problems. Genetic and environmental vulnerabilities are factors in the emergence of substance use disorders. Empirical evidence regarding the gene-environment interaction in substance use is mixed. Summaries of the latest findings from a candidate gene approach will be useful for revealing the significance of particular gene contributions. Thus, we aim to identify different gene-environment interactions in patterns of substance use and investigate whether any effects trend notably across different genders and races.MethodsWe reviewed published studies, until March 1, 2022, on substance use for candidate gene-environment interaction. Basic demographics of the included studies, target genes, environmental factors, main findings, patterns of gene-environment interaction, and other relevant information were collected and summarized.ResultsAmong a total of 44 studies, 38 demonstrated at least one significant interaction effect. About 61.5% of studies on the 5-HTTLPR gene, 100% on the MAOA gene, 42.9% on the DRD2 gene, 50% on the DRD4 gene, 50% on the DAT gene, 80% on the CRHR1 gene, 100% on the OPRM1 gene, 100% on the GABRA1 gene, and 50% on the CHRNA gene had a significant gene-environment interaction effect. The diathesis-stress model represents a dominant interaction pattern (89.5%) in the studies with a significant interaction effect; the remaining significant effect on substance use is found in the differential susceptibility model. The social push and swing model were not reported in the included studies.ConclusionThe gene-environment interaction research on substance use behavior is methodologically multidimensional, which causes difficulty in conducting pooled analysis, or stated differently-making it hard to identify single sources of significant influence over maladaptive patterns of drug taking. In decreasing the heterogeneity and facilitating future pooled analysis, researchers must (1) replicate the existing studies with consistent study designs and measures, (2) conduct power calculations to report gene-environment correlations, (3) control for covariates, and (4) generate theory-based hypotheses with factorial based experiments when designing future studies.

Project description:BackgroundModifications to lifestyle risk factors for stroke may help prevent stroke events. This systematic review aimed to identify and summarise the evidence of acupuncture interventions for those people with lifestyle risk factors for stroke, including alcohol-dependence, smoking-dependence, hypertension, and obesity.MethodsMEDLINE, CINAHL/EBSCO, SCOPUS, and Cochrane Database were searched from January 1996 to December 2016. Only randomised controlled trials (RCTs) with empirical research findings were included. PRISMA guidelines were followed and risk of bias was assessed via the Cochrane Collaboration risk of bias assessment tool. The systematic review reported in this paper has been registered on the PROSPERO (#CRD42017060490).ResultsA total of 59 RCTs (5,650 participants) examining the use of acupuncture in treating lifestyle risk factors for stroke met the inclusion criteria. The seven RCTs focusing on alcohol-dependence showed substantial heterogeneity regarding intervention details. No evidence from meta-analysis has been found regarding post-intervention or long-term effect on blood pressure control for acupuncture compared to sham intervention. Relative to sham acupuncture, individuals receiving auricular acupressure for smoking-dependence reported lower numbers of consumed cigarettes per day (two RCTs, mean difference (MD) = -2.75 cigarettes/day; 95% confidence interval (CI) = -5.33, -0.17; p = 0.04). Compared to sham acupuncture those receiving acupuncture for obesity reported lower waist circumference (five RCTs, MD = -2.79 cm; 95% CI: -4.13, -1.46; p<0.001). Overall, only few trials were considered of low risk of bias for smoking-dependence and obesity, and as such none of the significant effects in favour of acupuncture interventions were robust against potential selection, performance, and detection bias.ConclusionsThis review found no convincing evidence for effects of acupuncture interventions for improving lifestyle risk factors for stroke.

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Gene-Environment Interactions Between PPARG2 Variant and Lifestyle Factors in Relation to Cancer RIsk: A Systematic Review

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