Association between dried fruit intake and pan-cancers incidence risk: A two-sample Mendelian randomization study

Abstract

BackgroundObservational studies have revealed that dried fruit intake may be associated with cancer incidence; however, confounding factors make the results prone to be disturbed. Therefore, we conducted a two-sample Mendelian randomization (MR) study to explore the causal relationship between dried fruit intake and 11 site-specific cancers.Materials and methodsForty-three single nucleoside polymers (SNPs) with robust genome-wide association study (GWAS) evidence, strongly correlated with dried fruit intake, were used as instrumental variables (IVs) in this study. The summary-level genetic datasets of site-specific cancers were obtained from the Oncoarray oral cavity and oropharyngeal cancer consortium, International Lung Cancer Consortium, Breast Cancer Association Consortium (BCAC), Ovarian Cancer Association Consortium, PanScan1, and GWAS of other scholars. We analyzed the causality between dried fruit intake and 11 site-specific cancers using the inverse-variance-weighted (IVW) and weighted median (WM) methods. For the results of the MR analysis, Cochran’s Q test was used to check for heterogeneity, and multiplicative random effects were used to evaluate the heterogeneity further. Gene pleiotropy was tested using MR-Egger regression and MR-PRESSO methods. In addition, the main results of this study were validated by using the summary statistical data from the FinnGen and UK Biobank databases, and adjusted body mass index (BMI), years of education, fresh fruit intake, and vitamin C using multivariable MR analysis to ensure the stability of the research results.ResultsThe evidence from IVW analyses showed that each increase of dried fruit intake by one standard deviation was statistically significantly associated with 82.68% decrease of oral cavity/pharyngeal cancer incidence risk (P = 0.0131), 67.01% decrease of lung cancer incidence risk (P = 0.0011), 77% decrease of squamous cell lung cancer incidence risk (P = 0.0026), 53.07% decrease of breast cancer incidence risk (P = 4.62 × 10–5), 39.72% decrease of ovarian cancer incidence risk (P = 0.0183), 97.26% decrease of pancreatic cancer incidence risk (P = 0.0280), 0.53% decrease of cervical cancer incidence risk (P = 0.0482); however, there was no significant effect on lung adenocarcinoma (P = 0.4343), endometrial cancer (P = 0.8742), thyroid cancer (P = 0.6352), prostate cancer (P = 0.5354), bladder cancer (P = 0.8996), and brain cancer (P = 0.8164). In the validation part of the study results, the causal relationship between dried fruit intake and lung cancer (P = 0.0043), squamous cell lung cancer (P = 0.0136), and breast cancer (P = 0.0192) was determined. After adjusting for the potential impact of confounders, the causal relationship between dried fruit intake and lung cancer (P = 0.0034), squamous cell lung cancer (P = 0.046), and breast cancer (P = 0.0001) remained. The sensitivity analysis showed that our results were stable and reliable.ConclusionThe intake of dried fruits may have a protective effect against some site-specific cancers. Therefore, health education and a reasonable adjustment of dietary proportions may help in the primary prevention of cancer.

The causal relationship between abdominal obesity and lower bone mineral density: A two-sample mendelian randomization study

“…To further exclude bias due to weak instrumental variables, we used F -statistics to assess the presence of weak instrumental variables. F -statistics ( F -statistics = β 2 /se 2 )is an index to evaluate the weakness of IVs, since IVW could be easily affected by weak IVs, so we removed weak IVs, namely, SNPs by F -statistics ≤ 10 based on previous studies ( Zhou et al, 2019 ; Nazarzadeh et al, 2020 ; Jin et al, 2022 ).…”

“…In traditional IVW regression, the intercept term in linear regression is forced to be zero, whereas the MR Egger regression estimates the intercept term in the regression equation. A statistically significant non-zero intercept term indicates the presence of directional bias in the selected genetic variants (assuming that pleiotropic effects change the effect in one direction) ( Figure 2A ) ( Jin et al, 2022 ; Xu et al, 2022 ). In most cases, IVW was used to assess causal effects.…”

“…In most cases, IVW was used to assess causal effects. Generally speaking, according to previous studies, when there was absence of heterogeneity and pleiotropy, IVW was the most suitable method for MR analysis, while MR-Egger was recommended when there was the absence of heterogeneity and presence of pleiotropy ( Nazarzadeh et al, 2020 ; Jin et al, 2022 ).…”

Dried Fruits, Nuts, and Cancer Risk and Survival: A Review of the Evidence and Future Research Directions

“…A two-sample Mendelian randomization study utilized ~500,000 samples from the UK Biobank database to investigate dried fruit intake and cancer risk [ 62 ]. In this data set, for one standard deviation increase in genetically predicted dried fruit intake, a reduced risk was observed for oral cavity/pharyngeal cancer, lung cancer, squamous cell lung cancer, breast cancer, pancreatic cancer, and cervical cancer [ 62 ].…”

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

“…Studies have shown that the consumption of dried fruit may have a protective effect against cancer. It is suggested that health education and reasonable adjustment of dietary ratios may contribute to the primary prevention of cancer ( 26 ). There is also a high-quality MR study on the association between processed meat and the risk of cancer.…”