Open Access Research article

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer

Viktor Komlósi1, Erika Hitre2, Éva Pap2, Vilmos Adleff2, Andrea Réti2, Éva Székely3, Anna Bíró4, Péter Rudnai5, Bernadette Schoket6, Judit Müller7, Béla Tóth8, Szabolcs Ottó2, Miklós Kásler2, Judit Kralovánszky2* and Barna Budai2

Author Affiliations

1 School of PhD studies, Pathological Sciences, Semmelweis University, Budapest, Hungary

2 Department of Clinical Research, National Institute of Oncology, Budapest, Hungary

3 Medical Department, "Szent István és Szent László" Hospital, Budapest, Hungary

4 Department of Cytogenetics and Immunology, National Institute of Chemical Safety, Budapest, Hungary

5 Department of Environmental Epidemiology, National Institute of Environmental Health, Budapest, Hungary

6 Department of Molecular Environmental Epidemiology, National Institute of Environmental Health, Budapest, Hungary

7 Second Department of Pediatrics, Semmelweis University, Budapest, Hungary

8 Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Budapest, Hungary

For all author emails, please log on.

BMC Cancer 2010, 10:525  doi:10.1186/1471-2407-10-525

Published: 4 October 2010



Association 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.


The 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.


There 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.


A 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.