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

Viktor Komlósi, E. Hitre, Éva Pap, Vilmos Adleff, Andrea Réti, Éva Székely, Anna Bíró, P. Rudnai, B. Schoket, J. Müller, B. Tóth, Szabolcs Ottó, M. Kásler, Judit Kralovánszky, Barna Budai

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: 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.Methods: 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.Results: 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.Conclusions: 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.

Original languageEnglish
Article number525
JournalBMC Cancer
Volume10
DOIs
Publication statusPublished - Oct 4 2010

Fingerprint

Glycine Hydroxymethyltransferase
Methylenetetrahydrofolate Reductase (NADPH2)
Colonic Neoplasms
Homocysteine
Alleles
Genotype
Rectal Neoplasms
Confidence Intervals
Tumor Biomarkers
Gene Dosage
Folic Acid
Restriction Fragment Length Polymorphisms
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Komlósi, V., Hitre, E., Pap, É., Adleff, V., Réti, A., Székely, É., ... Budai, B. (2010). SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer. BMC Cancer, 10, [525]. https://doi.org/10.1186/1471-2407-10-525

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer. / Komlósi, Viktor; Hitre, E.; Pap, Éva; Adleff, Vilmos; Réti, Andrea; Székely, Éva; Bíró, Anna; Rudnai, P.; Schoket, B.; Müller, J.; Tóth, B.; Ottó, Szabolcs; Kásler, M.; Kralovánszky, Judit; Budai, Barna.

In: BMC Cancer, Vol. 10, 525, 04.10.2010.

Research output: Contribution to journalArticle

Komlósi, V, Hitre, E, Pap, É, Adleff, V, Réti, A, Székely, É, Bíró, A, Rudnai, P, Schoket, B, Müller, J, Tóth, B, Ottó, S, Kásler, M, Kralovánszky, J & Budai, B 2010, 'SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer', BMC Cancer, vol. 10, 525. https://doi.org/10.1186/1471-2407-10-525
Komlósi, Viktor ; Hitre, E. ; Pap, Éva ; Adleff, Vilmos ; Réti, Andrea ; Székely, Éva ; Bíró, Anna ; Rudnai, P. ; Schoket, B. ; Müller, J. ; Tóth, B. ; Ottó, Szabolcs ; Kásler, M. ; Kralovánszky, Judit ; Budai, Barna. / SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer. In: BMC Cancer. 2010 ; Vol. 10.
@article{1c42865b7ea444eb8818ead3f6002883,
title = "SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer",
abstract = "Background: 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.Methods: 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.Results: 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.Conclusions: 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.",
author = "Viktor Koml{\'o}si and E. Hitre and {\'E}va Pap and Vilmos Adleff and Andrea R{\'e}ti and {\'E}va Sz{\'e}kely and Anna B{\'i}r{\'o} and P. Rudnai and B. Schoket and J. M{\"u}ller and B. T{\'o}th and Szabolcs Ott{\'o} and M. K{\'a}sler and Judit Kralov{\'a}nszky and Barna Budai",
year = "2010",
month = "10",
day = "4",
doi = "10.1186/1471-2407-10-525",
language = "English",
volume = "10",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",

}

TY - JOUR

T1 - SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer

AU - Komlósi, Viktor

AU - Hitre, E.

AU - Pap, Éva

AU - Adleff, Vilmos

AU - Réti, Andrea

AU - Székely, Éva

AU - Bíró, Anna

AU - Rudnai, P.

AU - Schoket, B.

AU - Müller, J.

AU - Tóth, B.

AU - Ottó, Szabolcs

AU - Kásler, M.

AU - Kralovánszky, Judit

AU - Budai, Barna

PY - 2010/10/4

Y1 - 2010/10/4

N2 - Background: 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.Methods: 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.Results: 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.Conclusions: 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.

AB - Background: 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.Methods: 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.Results: 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.Conclusions: 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.

UR - http://www.scopus.com/inward/record.url?scp=77957286796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957286796&partnerID=8YFLogxK

U2 - 10.1186/1471-2407-10-525

DO - 10.1186/1471-2407-10-525

M3 - Article

C2 - 20920350

AN - SCOPUS:77957286796

VL - 10

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

M1 - 525

ER -