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Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study.
Prostate. 2010 Nov 01; 70(15):1645-57.P

Abstract

BACKGROUND

We hypothesized that genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene are associated with prostate cancer risk.

METHODS

We genotyped three MTHFR polymorphisms (C677T, A1298C, and G1793A) and measured serum total homocysteine (tHcy), folate, and vitamin B12 levels in a case-control study of 174 cases and 348 normal healthy controls. The cancer-free controls were frequency matched to the cases by age (±2 years), educational level, occupational status, ethnicity, and smoking status.

RESULTS

We found that the MTHFR 677TT and 1298CC genotypes were associated with an about 40% reduction in risk of prostate cancer (adjusted OR = 0.59, 95% CI = 0.41-0.94, and adjusted OR = 0.58, 95% CI = 0.32-0.91, respectively) compared to the 677CC, and 1298AA genotypes. The combined variant genotypes of 1298AC + 677CC were associated with a 30% reduction in risk of prostate cancer (OR = 0.70; 95% CI = 0.53-0.79). In contrast, the variant genotypes of 1793GA + 677CT were associated with slightly increased risk for prostate cancer (OR = 1.64; 95% CI = 0.86-2.15). Regarding prostate cancer aggressiveness, the 677TT genotype was associated with more than 50% decreased risk of high-grade prostate cancer (Gleason score >7) compared with the 677CC and 677CT genotypes (OR = 0.35, 95% CI = 0.24-0.64; P = 0.001). There was no significant difference in plasma levels of tHcy, folate, and vitamin B12 between the two groups with any genotypes.

CONCLUSION

These data suggest that all three MTHFR polymorphisms may play a pivotal role in the developing prostate cancer. Larger studies in different ethnic populations and incorporating dietary folate intake are needed to replicate our findings.

Authors+Show Affiliations

Urology and Nephrology Research Center, Shahid Beheshti University (MC), Tehran, Iran. safarinejad@unrc.irNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20564317

Citation

Safarinejad, Mohammad Reza, et al. "Relationship Between Three Polymorphisms of Methylenetetrahydrofolate Reductase (MTHFR C677T, A1298C, and G1793A) Gene and Risk of Prostate Cancer: a Case-control Study." The Prostate, vol. 70, no. 15, 2010, pp. 1645-57.
Safarinejad MR, Shafiei N, Safarinejad S. Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. Prostate. 2010;70(15):1645-57.
Safarinejad, M. R., Shafiei, N., & Safarinejad, S. (2010). Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. The Prostate, 70(15), 1645-57. https://doi.org/10.1002/pros.21200
Safarinejad MR, Shafiei N, Safarinejad S. Relationship Between Three Polymorphisms of Methylenetetrahydrofolate Reductase (MTHFR C677T, A1298C, and G1793A) Gene and Risk of Prostate Cancer: a Case-control Study. Prostate. 2010 Nov 1;70(15):1645-57. PubMed PMID: 20564317.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. AU - Safarinejad,Mohammad Reza, AU - Shafiei,Nayyer, AU - Safarinejad,Shiva, PY - 2010/6/22/entrez PY - 2010/6/22/pubmed PY - 2010/10/26/medline SP - 1645 EP - 57 JF - The Prostate JO - Prostate VL - 70 IS - 15 N2 - BACKGROUND: We hypothesized that genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene are associated with prostate cancer risk. METHODS: We genotyped three MTHFR polymorphisms (C677T, A1298C, and G1793A) and measured serum total homocysteine (tHcy), folate, and vitamin B12 levels in a case-control study of 174 cases and 348 normal healthy controls. The cancer-free controls were frequency matched to the cases by age (±2 years), educational level, occupational status, ethnicity, and smoking status. RESULTS: We found that the MTHFR 677TT and 1298CC genotypes were associated with an about 40% reduction in risk of prostate cancer (adjusted OR = 0.59, 95% CI = 0.41-0.94, and adjusted OR = 0.58, 95% CI = 0.32-0.91, respectively) compared to the 677CC, and 1298AA genotypes. The combined variant genotypes of 1298AC + 677CC were associated with a 30% reduction in risk of prostate cancer (OR = 0.70; 95% CI = 0.53-0.79). In contrast, the variant genotypes of 1793GA + 677CT were associated with slightly increased risk for prostate cancer (OR = 1.64; 95% CI = 0.86-2.15). Regarding prostate cancer aggressiveness, the 677TT genotype was associated with more than 50% decreased risk of high-grade prostate cancer (Gleason score >7) compared with the 677CC and 677CT genotypes (OR = 0.35, 95% CI = 0.24-0.64; P = 0.001). There was no significant difference in plasma levels of tHcy, folate, and vitamin B12 between the two groups with any genotypes. CONCLUSION: These data suggest that all three MTHFR polymorphisms may play a pivotal role in the developing prostate cancer. Larger studies in different ethnic populations and incorporating dietary folate intake are needed to replicate our findings. SN - 1097-0045 UR - https://www.unboundmedicine.com/medline/citation/20564317/Relationship_between_three_polymorphisms_of_methylenetetrahydrofolate_reductase__MTHFR_C677T_A1298C_and_G1793A__gene_and_risk_of_prostate_cancer:_a_case_control_study_ L2 - https://doi.org/10.1002/pros.21200 DB - PRIME DP - Unbound Medicine ER -