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

Abstract

Background: Observational 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 methods: Forty-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.

Results: The 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.

Conclusion: The 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.

Keywords: Mendelian randomization; causal relationship; dried fruit intake; incidence risk; site-specific cancers.

FIGURE 1

Directed acyclic graph of Mendelian randomization (MR) framework showing the hypothesis of dried fruit intake on site-specific cancers, the dotted line indicates that there has pleiotropic or direct causal relationship between exposure and outcome.

FIGURE 2

Manhattan plot of 43 SNPs identified as instrumental variables (IVs) from exposure dataset. SNP, single nucleotide polymorphism.

FIGURE 3

Forest plot of two-sample Mendelian randomization (MR) estimation of the association between dried fruit intake and cancer risk. No. of SNPs, number of single nucleotide polymorphisms; CI, confidence interval.

FIGURE 4

Forest plots of multivariable Mendelian randomization (MR) in (A) lung cancer, (B) squamous cell lung cancer, and (C) breast cancer. Adjusted for fresh fruit intake, vitamin C, body mass index, years of education or fresh fruit intake, vitamin C, body mass index, and years of education.

FIGURE 5

Forest plot of two-sample Mendelian randomization (MR) estimation of the association between dried fruit intake and cancer risk in validation datasets. No. of SNPs, number of single nucleotide polymorphisms; CI, confidence interval.