A significantly stronger association between betaine and the risk of total cancer was found for younger participants (age < 65y), females, those with low folate (< 7.19 ng/mL), MTHFR rs1801133 (CT), current alcohol consumption, high total cholesterol (≥ 5.54 mmol/L), low triglycerides (< 1.69 mmol/L), and high high-density lipoprotein cholesterol (≥ 1.04 mmol/L). Here, MTHFR is linked to cancer.