Table 1.
Summary of studies examining the relationship between dietary factors and DNA methylation in cancer patients.
| First Author and Year of Publication | Country | Study Design | Study Population | Dietary Factors | DNA Methylation Markers | Sample Type | DNA Methylation Method | Main Findings |
|---|---|---|---|---|---|---|---|---|
| van Engeland et al. 2003 [33] | The Netherlands | Cross-sectional | 122 patients with colorectal cancer | Alcohol and folate | APC, p14, p16, MLH1, MGMT, and RASSF1A | Tumor biopsy | Methylation Specific PCR | For each gene, prevalence of promoter hypermethylation was higher in patients with low folate intake and high alcohol consumption. The number of patients with at least one gene methylated was higher in the low folate intake/high alcohol intake group than their counterparts |
| Nan et al. 2004 [34] | Korea | Case Control | 110 patients with gastric cancer and 220 age- and sex-matched controls |
Foods, calories, nutrients, vitamins, and minerals | MLH1 | Tumor biopsy | Methylation Specific PCR | Alcohol consumption was associated with higher odds of MLH1 hypermethylation. High consumption of vegetables and low consumption of potato were associated with higher odds of MLH1 hypermethylation |
| Yuasa et al. 2005 [35] | Japan | Cross-sectional | 73 patients with gastric cancer | Foods and nutrients | CDX2, p16 and MLH1 | Tumor biopsy | Methylation Specific PCR | Among men, consumption of green tea and cruciferous vegetables was negatively correlated with CDX2 methylation |
| Kraunz et al. 2006 [36] | USA | Cross-sectional | 242 patients with head and neck squamous cell carcinoma | Folate | p16 | Tumor biopsy | Methylation Specific PCR | Low intake of folate was associated with higher odds of p16 methylation |
| Slattery et al. 2006 [37] | USA | Case Control | 1154 patients with colon cancer and 1256 controls | Cruciferous vegetables, alcohol, folate, vitamins B6 and B12, methionine, and fiber |
CIMP | Tumor biopsy | Methylation Specific PCR | Alcohol consumption was associated with higher odds of CIMP-low. The intake of fiber was associated with CIMP status |
| Mas et al. 2007 [38] | Spain | Case Control | 120 patients with colorectal cancer and 296 controls | Nutrients | p16, p14 and MLH1 | Tumor biopsy | Methylation Specific PCR | Patients with low intake of folate, vitamin A, vitamin B1, potassium and iron showed lower p16 methylation than controls. Patients with low vitamin A intake showed lower p14 and MLH1 methylation |
| De Vogel et al. 2008 [39] | The Netherlands | Cross-sectional | 648 patients with colorectal cancer | Folate, vitamin B2 and vitamin B6, methionine and alcohol | MLH1 | Tumor biopsy | Methylation Specific PCR | Intakes of folate, vitamin B2, methionine and alcohol were not associated with MLH1 hypermethylation. Among men, intake of vitamin B6 was associated with MLH1 hypermethylation |
| Schernhammer et al. 2009 [40] | USA | Cross-sectional | 609 patients with colon cancer | Alcohol, folate and B vitamins | LINE-1 | Tumor biopsy | Pyrosequencing | Participants with higher folate intake were less likely to exhibit LINE-1 hypomethylation. Alcohol consumption was positively associated with LINE-1 hypomethylation |
| Curtin et al. 2011 [41] | USA | Case Control | 951 patients with rectal cancer and 1205 controls | Folate, riboflavin, vitamins B6 andB12, and methionine | CIMP | Tumor biopsy | Methylation Specific PCR | Women with higher folate intake had lower odds of CIMP+ phenotype. Men with higher folate intake had higher odds of CIMP+ tumor |
| Tao et al. 2011 [42] | USA | Cross-sectional | 1170 women with breast cancer | One-carbon-related micronutrients and compounds | E-cadherin, p16, and RAR-β | Tumor biopsy | Methylation Specific PCR | Dietary intake of folate, vitamins B2, B6, B12, and methionine was not associated with methylation of E- cadherin, p16, and RAR-β |
| Xu et al. 2011 [43] | USA | Cross-sectional | 851 women with breast cancer | One-carbon-related micronutrients and compounds | 13 breast cancer-related genes | Tumor biopsy | Methylation Specific PCR and Methyight assay | Intake of B2 and B6 correlated with promoter methylation status in 3 out of the 13 breast cancer genes evaluated. Both positive (hypermethylation) and inverse (hypomethylation) associations were observed |
| Piyathilake et al. 2012 [19] | USA | Cross-sectional | 319 women with abnormal cervical cytology | Dietary patterns | LINE-1 | Blood | Pyrosequencing | Women with healthy dietary pattern were more likely to have higher LINE-1 methylation than those who adhered to an unhealthy dietary pattern |
| Zhang et al. 2013 [44] | South Korea | Cross-sectional | 184 patients with gastric cancer | Calories, foods, nutrients, vitamins and minerals | RUNX3 | Tumor biopsy | Methylation Specific PCR | High consumption of eggs was associated with higher odds of RUNX3 methylation. High consumption of nuts was associated with higher odds of RUNX3 methylation in patients with Helicobacter pylori infection. High consumption of fruits and high intake of carbohydrate, vitamin B1, and vitamin E was associated with lower odds of RUNX3 methylation |
| Chen et al. 2014 [45] | China | Case Control | 90 patients with esophageal squamous cell carcinoma and 60 healthy adults | Roast meat | p16 | Esophageal mucosa tissue | Pyrosequencing | Consumption of roast meat was positively associated with p16 methylation among cases. No association was evident among healthy subjects |
| Nishihara et al. 2014 [46] | USA | Cross-sectional | 993 patients with colorectal cancer from the Nurses’ Health Study and the Health Professionals’ Follow-up Study | Alcohol, vitamin B6, vitamin B12, folate, and methionine | IGF2 | Tumor biopsy | Pyrosequencing | Consumption of >15 g alcohol/d was associated with higher risk of colorectal cancer with lower IGF2 methylation levels. The association of vitamin B-6, vitamin B-12, and folate intakes with cancer risk did not significantly differ according to IGF2 methylation level |
| Pirouzpanah et al. 2015 [47] | Iran | Cross-sectional | 149 women with breast cancer | Folate, vitamins B2, B6, B12, and methionine | RAR-β, BRCA1 and RASSF1A | Tumor biopsy | Methylation Specific PCR | Intake of folate and vitamin B12 was negatively associated with RAR-β and BRCA1 methylation. Intake of riboflavin and pyridoxine was positively associated with RAR-β methylation |
| Mehta et al. 2017 [48] | USA | Cross-sectional | 1285 patients with colorectal cancer from the Health Professionals’ Follow-up Study and the Nurses’ Health Study | Dietary patterns | CIMP | Tumor biopsy | Pyrosequencing | Adherence to the western dietary pattern, characterized by red and processed meats, high-fat dairy products, refined grains, and desserts, was associated with CIMP-low phenotype |
| Ferrari et al. 2019 [49] | Brazil | Cross-sectional | 189 patients with colon or rectal adenocarcinoma | Alcohol, folate, vitamins B2, B6, and B12, choline, betaine, methionine, energy, carbohydrate, protein, and lipid | Global DNA methylation | Tumor biopsy and blood | Enzyme-linked immunosorbent assay | No association between dietary intakes and global DNA methylation was evident |