Homocysteine levels and cancer risk in hypertensive adults across MTHFR C677T genotypes

Metabolic factors, such as homocysteine (Hcy) metabolism, are believed to influence cancer risk. The MTHFR C677T polymorphism, which raises Hcy levels by affecting folate metabolism, has been associated with varying cancer risks. However, previous studies have not fully explored the interaction between Hcy levels and MTHFR C677T genotypes in relation to cancer risk. This nested case-control study within the China H-Type Hypertension Registry Study (CHHRS) included 1,219 cancer patients and 1,219 matched controls. Serum Hcy and MTHFR C677T genotypes were assessed, and odds ratios (ORs) with 95% confidence intervals (CIs) for cancer risk were calculated using conditional logistic regression. In univariate analyses, each standard deviation increase in Hcy was linked to a 10% higher cancer risk (OR = 1.10, 95% CI: 1.01–1.20). In tertile analyses, the highest tertile was associated with a significantly higher cancer risk in the TT genotype subgroup (OR = 1.82, 95% CI: 1.17–2.84). For site-specific cancers, in the TT genotype subgroup, each SD increase in Hcy was associated with higher risks of non-digestive cancers (OR 1.74, 95% CI 1.19–2.54) and non-digestive cancers excluding lung (OR 2.69, 95% CI 1.47–4.91). In tertile analyses (T3 vs. T1), risks were elevated for lung (OR 2.34, 95% CI 1.82–5.12), digestive (OR 1.81, 95% CI 1.02–3.17), non-digestive (OR 2.05, 95% CI 1.14–3.69), and non-digestive excluding lung cancers (OR 2.32, 95% CI 1.04–5.21). Elevated Hcy levels are associated with an increased cancer risk, especially among individuals with the MTHFR C677T TT genotype. Further studies are needed to confirm these findings and explore the underlying mechanisms.