SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancerReportar como inadecuado




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BMC Cancer

, 10:525

Genetics, genomics and epigenetics

Abstract

BackgroundAssociation between rectal or colon cancer risk and serine hydroxymethyltransferase 1 SHMT1 C1420T or methylenetetrahydrofolate reductase MTHFR C677T polymorphisms was assessed. The serum total homocysteine HCY, marker of folate metabolism was also investigated.

MethodsThe SHMT1 and MTHFR genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated.

ResultsThere was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for SHMT1 TT OR = 0.57, 95% confidence interval CI 0.36-0.89 and higher for MTHFR CT genotypes OR = 1.4, 95%CI 1.06-1.84. A gene-dosage effect was observed for SHMT1 with progressively decreasing risk with increasing number of T allele p = 0.014. The stratified analysis according to age and sex revealed that the association is mainly present in the younger < 60 years or male subgroup. As expected from genotype analysis, the SHMT1 T allele-MTHFR CC diplotype was associated with reduced rectal cancer risk OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together. The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by SHMT1 polymorphism, while in patients it was affected only by Dukes- stage. In patients with Dukes- stage C or D HCY can be considered as a tumor marker only in case of SHMT1 1420CC genotypes.

ConclusionsA protective effect of SHMT1 1420T allele or SHMT1 1420 T allele-MTHFR 677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of SHMT1 1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in SHMT1 1420 wild-type CC CRC patients in Dukes- stage C and D. Further studies need to clarify why SHMT1 and MTHFR polymorphisms are associated only with rectal and not colon cancer risk.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-525 contains supplementary material, which is available to authorized users.

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Autor: Viktor Komlósi - Erika Hitre - Éva Pap - Vilmos Adleff - Andrea Réti - Éva Székely - Anna Bíró - Péter Rudnai - Be

Fuente: https://link.springer.com/







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