Jin Chen, Li Rui, Deng Tuo, Lin Zixia, Li Haoqi, Yang Yan, Su Qing, Wang Jingxian, Yang Yi, Wang Juejin, Chen Gang, Wang Yi
Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Front Nutr. 2022 Jul 18;9:899137. doi: 10.3389/fnut.2022.899137. eCollection 2022.
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.
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 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.
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 ( = 0.0131), 67.01% decrease of lung cancer incidence risk ( = 0.0011), 77% decrease of squamous cell lung cancer incidence risk ( = 0.0026), 53.07% decrease of breast cancer incidence risk ( = 4.62 × 10), 39.72% decrease of ovarian cancer incidence risk ( = 0.0183), 97.26% decrease of pancreatic cancer incidence risk ( = 0.0280), 0.53% decrease of cervical cancer incidence risk ( = 0.0482); however, there was no significant effect on lung adenocarcinoma ( = 0.4343), endometrial cancer ( = 0.8742), thyroid cancer ( = 0.6352), prostate cancer ( = 0.5354), bladder cancer ( = 0.8996), and brain cancer ( = 0.8164). In the validation part of the study results, the causal relationship between dried fruit intake and lung cancer ( = 0.0043), squamous cell lung cancer ( = 0.0136), and breast cancer ( = 0.0192) was determined. After adjusting for the potential impact of confounders, the causal relationship between dried fruit intake and lung cancer ( = 0.0034), squamous cell lung cancer ( = 0.046), and breast cancer ( = 0.0001) remained. The sensitivity analysis showed that our results were stable and reliable.
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.
观察性研究表明，食用果干可能与癌症发病率有关；然而，混杂因素使结果容易受到干扰。因此，我们进行了一项两样本孟德尔随机化（MR）研究，以探讨食用果干与11种特定部位癌症之间的因果关系。
本研究使用了43个单核苷酸多态性（SNP）作为工具变量（IV），这些SNP具有可靠的全基因组关联研究（GWAS）证据，且与果干摄入量密切相关。特定部位癌症的汇总水平遗传数据集来自口腔和口咽癌联盟的Oncoarray、国际肺癌联盟、乳腺癌协会联盟（BCAC）、卵巢癌协会联盟、PanScan1以及其他学者的GWAS。我们使用逆方差加权（IVW）和加权中位数（WM）方法分析了食用果干与11种特定部位癌症之间的因果关系。对于MR分析的结果，使用Cochran's Q检验检查异质性，并使用乘性随机效应进一步评估异质性。使用MR-Egger回归和MR-PRESSO方法检验基因多效性。此外，本研究的主要结果通过使用来自芬兰基因库（FinnGen）和英国生物银行（UK Biobank）数据库的汇总统计数据进行了验证，并通过多变量MR分析调整了体重指数（BMI）、受教育年限、新鲜水果摄入量和维生素C，以确保研究结果的稳定性。
IVW分析的证据表明，果干摄入量每增加一个标准差，口腔/咽癌发病风险降低82.68%（P = 0.0131），肺癌发病风险降低67.01%（P = 0.0011），肺鳞状细胞癌发病风险降低77%（P = 0.0026），乳腺癌发病风险降低53.07%（P = 4.62×10⁻⁴），卵巢癌发病风险降低39.72%（P = 0.0183），胰腺癌发病风险降低97.26%（P = 0.0280），宫颈癌发病风险降低0.53%（P = 0.0482）；然而，对肺腺癌（P = 0.4343）、子宫内膜癌（P = 0.8742）、甲状腺癌（P = 0.6352）、前列腺癌（P = 0.5354）、膀胱癌（P = 0.8996）和脑癌（P = 0.8164）没有显著影响。在研究结果的验证部分，确定了果干摄入量与肺癌（P = 0.0043）、肺鳞状细胞癌（P = 0.0136）和乳腺癌（P = 0.0192）之间的因果关系。在调整混杂因素的潜在影响后，果干摄入量与肺癌（P = 0.0034）、肺鳞状细胞癌（P = 0.046）和乳腺癌（P = 0.0001）之间的因果关系仍然存在。敏感性分析表明，我们的结果稳定可靠。
食用果干可能对某些特定部位的癌症具有保护作用。因此，健康教育和合理调整饮食比例可能有助于癌症的一级预防。
