scholarly journals Interactions Between Folate Intake and Genetic Predictors of Gene Expression Levels Associated with Colorectal Cancer Risk

2021 ◽  
Author(s):  
Cameron B. Haas ◽  
Yu-Ru Su ◽  
Paneen Petersen ◽  
Xiaoliang Wang ◽  
Stephanie A Bien ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cancer Risk ◽  
Colorectal Cancer Risk ◽  
Cellular Damage ◽  
Folate Intake ◽  
European Ancestry ◽  
Specific Gene ◽  
Case Control Studies ◽  
Colon Tissue

Abstract Background Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (GxE) interactions and may provide information on the underlying biological pathway. Objective We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. Methods We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based GxE approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4,839 genes with available genetically predicted expression. We meta-analyzed results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. Results We found suggestive evidence of interaction with folate intake for genes including glutathione S-Transferase Alpha 1 (GSTA1; p=4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p=4.3E-4), and Aspartylglucosaminidase (AGA: p=4.5E-4). Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein. Conclusion We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk.

scholarly journals Association Between Blood Circulating Vitamin D and Colorectal Cancer Risk in Asian Countries: A Systematic Review and Dose-Response Meta-analysis

2019 ◽  
Author(s):  
Lin Zhang ◽  
Huachun Zou ◽  
Yang Zhao ◽  
Chunlei Hu ◽  
Adejare (Jay) Atanda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Risk ◽  
Dose Response ◽  
Meta Analysis ◽  
Asian Population ◽  
Colorectal Cancer Risk ◽  
Asian Countries ◽  
Case Control Studies ◽  
Vitamin D Levels

ABSTRACTObjectivesTo assess the association between blood circulating Vitamin D levels and colorectal cancer risk in the Asian population.DesignThis is a systematic review and dose-response meta-analysis of observational studies that investigated the relationship between blood circulating Vitamin D levels and colorectal cancer risk in the Asian population.Data SourcesRelevant studies were identified through a literature search in MEDLINE, EMBASE, and Web of Science from January 1980 to 31 January 2019. Eligibility criteria: original studies published in peer-reviewed journals investigating the association between blood circulating Vitamin D levels and the risk of colorectal cancer and/or adenoma in Asian countries.Data extraction and synthesisTwo authors independently extracted data and assessed the quality of included studies. Study-specific ORs were pooled using a random-effects model. A dose-response meta-analysis was performed with generalized least squares regression. We applied the Newcastle-Ottawa Scale quality assessment to evaluate the quality of the selected studies.ResultsThe eight included studies encompassed a total of 2,916 cases and 6,678 controls. The pooled ORs of colorectal cancer for the highest versus lowest categories of blood circulating Vitamin D levels was 0.75 [95% CI, 0.58-0.97] up to 36.5 ng/mL in the Asian population. There was heterogeneity among the studies (I2=53.9%, Pheterogeneity=0.034). The dose-response meta-analysis indicated a significant linear relationship (Pnon-linearity=0.11). An increment of 16 ng/mL in blood circulating Vitamin D level corresponded to an OR of 0.79 [95% CI, 0.64-0.97].ConclusionsThe results of this meta□analysis indicate that blood circulating Vitamin D level is associated with decreased risk of colorectal cancer in Asian countries. The dose-response meta-analysis shows that the strength of this association among the Asian population is similar to that among the Western population. Our study suggests that the Asian population should improve nutritional status and maintain a higher level of blood circulating Vitamin D.Strengths and limitations of this studyOur study seeks to extend previous work by including a number of new studies and by distinguishing the Asian population explicitly.The number of included studies is not sufficient to provide a robust estimate, so the results should be interpreted in the context of the limitations of the available data.Heterogeneous definitions of blood circulating Vitamin D categories were used across studies. The variability in definitions could limit comparability between studies.Our study included seven case-control studies; the study design implies that the measurement of blood circulating Vitamin D is measured in individuals already diagnosed with colorectal cancer. Results from case-control studies need to be interpreted cautiously because of the potential for reverse causation.Time of blood sampling in relation to outcome ascertainment also varied among studies. Such cross-sectional measurements may not accurately reflect an individual’s Vitamin D status across time.

scholarly journals Type 2 Diabetes, Antidiabetic Medications, and Colorectal Cancer Risk: Two Case–Control Studies from Italy and Spain

2016 ◽  
Vol 6 ◽  
Author(s):  
Valentina Rosato ◽  
Alessandra Tavani ◽  
Esther Gracia-Lavedan ◽  
Elisabet Guinó ◽  
Gemma Castaño-Vinyals ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Cancer Risk ◽  
Case Control ◽  
Colorectal Cancer Risk ◽  
Case Control Studies

scholarly journals SMAD7 polymorphisms and colorectal cancer risk: a meta-analysis of case-control studies

Oncotarget ◽  
2016 ◽  
Vol 7 (46) ◽  
pp. 75561-75570 ◽  
Author(s):  
Yongsheng Huang ◽  
Wenting Wu ◽  
Meng Nie ◽  
Chuang Li ◽  
Lin Wang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Case Control ◽  
Colorectal Cancer Risk ◽  
Case Control Studies

Association between XRCC1 and XRCC3 polymorphisms and colorectal cancer risk: a meta-analysis of 23 case–control studies

2012 ◽  
Vol 40 (6) ◽  
pp. 3943-3952 ◽  
Author(s):  
Li Liu ◽  
Lin Miao ◽  
Guozhong Ji ◽  
Fulin Qiang ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Case Control ◽  
Colorectal Cancer Risk ◽  
Case Control Studies

scholarly journals Garlic consumption and colorectal cancer risk in man: a systematic review and meta-analysis

2015 ◽  
Vol 19 (2) ◽  
pp. 308-317 ◽  
Author(s):  
Manuela Chiavarini ◽  
Liliana Minelli ◽  
Roberto Fabiani
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Pooled Analysis ◽  
Case Control ◽  
Dietary Factors ◽  
Colorectal Cancer Risk ◽  
Risk Estimate ◽  
Case Control Studies

AbstractObjectiveColorectal cancer shows large incidence variations worldwide that have been attributed to different dietary factors. We conducted a meta-analysis on the relationship between garlic consumption and colorectal cancer risk.DesignWe systematically reviewed publications obtained by searching ISI Web of Knowledge, MEDLINE and EMBASE literature databases. We extracted the risk estimate of the highest and the lowest reported categories of intake from each study and conducted meta-analysis using a random-effects model.ResultsThe pooled analysis of all fourteen studies, seven cohort and seven case–control, indicated that garlic consumption was not associated with colorectal cancer risk (OR=0·93; 95 % CI 0·82, 1·06, P=0·281; I2=83·6 %, P≤0·001). Separate analyses on the basis of cancer sites and sex also revealed no statistically significant effects on cancer risk. However, when separately analysed on the basis of study type, we found that garlic was associated with an approximately 37 % reduction in colorectal cancer risk in the case–control studies (combined risk estimate=0·63, 95 % CI 0·48, 0·82, P=0·001; I2=75·6 %, P≤0·001).ConclusionsOur results suggest that consumption of garlic is not associated with a reduced colorectal cancer risk. Further investigations are necessary to clarify the discrepancy between results obtained from different types of epidemiological studies.

scholarly journals Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study

2021 ◽  
Author(s):  
Xiaomeng Zhang ◽  
Evropi Theodoratou ◽  
Xue Li ◽  
Susan M. Farrington ◽  
Philip J. Law ◽  
...  
Keyword(s):  
Physical Activity ◽  
Colorectal Cancer ◽  
Cancer Risk ◽  
Body Fat ◽  
Instrumental Variables ◽  
Sedentary Time ◽  
Colorectal Cancer Risk ◽  
European Ancestry ◽  
Mendelian Randomisation ◽  
Mr Study

Abstract Background We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat. Methods Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs. Results We found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively. Conclusion These findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.

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