Association of Methylenetetrahydrofolate Reductase Gene rs1801133 Polymorphism and Controlling Nutritional Status (CONUT) Score with Colorectal Cancer Susceptibility

Background: Susceptibility to some cancers is linked to methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the Controlling Nutritional Status (CONUT) score in some populations. However, their relationship with susceptibility to colorectal cancer (CRC) susceptibility in the Hakka Chinese population remains unclear.

Methods: In total, 620 CRC patients and 734 controls were enrolled. MTHFR rs1801133 was genotyped, medical records (age, sex, smoking history, alcohol consumption, hypertension, diabetes mellitus, and family history of cancer, and blood cell parameters) were collected, and the relationship between this information and CRC susceptibility was analyzed.

Results: There were significant differences in the distribution of CONUT classification (p=0.002), and proportions of history of smoking (p<0.001), hypertension (p<0.001), diabetes mellitus (p<0.001), and family history of cancer (p=0.002) between patients and controls. There were statistically significant differences in MTHFR rs1801133 genotypes distribution (58.7% C/C, 35.5% C/T, and 5.8% T/T in patients vs 65.5%, 31.2%, and 3.3% in controls, p=0.010) and allele distribution (76.5% C, and 23.5% T allele in patients vs 81.1%, and 18.9% in controls, p=0.003) between patients and controls. Logistic regression analysis indicated that non-normal CONUT range (non-normal vs normal, odds ratio (OR): 1.451, 95% confidence interval (CI): 1.119-1.882, p=0.005), and MTHFR rs1801133 variant (C/T + T/T vs C/C, OR: 1.373, 95% CI: 1.091-1.728, p=0.007), older age (≥65 vs <65 years, OR: 1.298, 95% CI: 1.023-1.646, p=0.032), male sex (OR: 1.354, 95% CI: 1.067-1.718, p=0.013), and history of alcohol drinking (OR: 2.232, 95% CI: 1.164-4.282, p=0.016) were independently associated with CRC risk.

Conclusion: Individuals carried MTHFR rs1801133 variant and with non-normal CONUT range, advanced age, history of alcohol consumption may be at increased CRC risk in the Hakka population.