Some genetic variants of the Methylenetetrahydrofolate Reductase (MTHFR) gene can lead to high levels of homocysteine and hinder the ability to process folate. Some genetic variants of this gene are related to susceptibility of many diseases such as cancer. Our aim has been to estimate the association between polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a Mediterranean population.
We have carried out an observational study at baseline and longitudinally in the PREDIMED-Valencia study including 398 men at high cardiovascular risk. We prospectively analyzed cancer incidence as a secondary outcome in this study. Lifestyle, clinical and biochemical variables were assessed by standardized methods. DNA was isolated from blood and the selected polymorphisms were determined.
We detected 21 new cases of prostate cancer from 2003 to 2014, representing 1.9% of all cancers and 5.3% of all cancer cases in men. The analysis of the risk of prostate cancer in the variants described was carried out grouping the carriers of the allele less frequent. The allelic frequency of the rs1476413 was 0.219 for not affected participants while it was 0.074 in the cases. The crude OR = 0.24 (95%CI 0.08-0.74) p = 0.013 and OR = 0.23 (95%CI 0.08-0.71) p = 0.010 after adjustment (by age, intervention group and smoking habit). For the rs1801131, the allelic frequency was 0.271 for not affected participants while it was 0,148 in the cases. The crude OR = 0.33 (95%CI 0.13-0.83) p = 0.019 and OR = 0.33 (95%CI 0.13-0.84) p = 0.020 after adjustment. For the rs4846052, the allelic frequency was 0.390 for not affected participants while it was 0.278 in the cases. The crude OR = 0.43 (95%CI 0.19-0.95) p = 0.038 and OR = 0.43 (95%CI 0.19-0.97) p = 0.043 after adjustment. For the rs6541003 was the allelic frequency was 0.380 for not affected participants while it was 0.259 in the cases. The crude OR = 0.39 (95%CI 0.17-0.87) p = 0.021 and OR 0.39 (95%CI 0.17-0.88) p = 0.023 after adjustment.
The rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene were protective against the development of prostate cancer in a high cardiovascular risk population.
Clinical trial identification
Legal entity responsible for the study
University of Valencia.
Instituto de Salud Carlos III.
All authors have declared no conflicts of interest.