title: Polymorphisms in methylenetetrahydrofolate reductase gene and risk of non-Hodgkin lymphoma in a multi-ethnic population.
abstract: An imbalance in folate metabolism can adversely affect DNA synthesis and methylation systems which can lead to susceptibility to non-Hodgkin lymphoma (NHL). Whether single nucleotide polymorphisms (SNPs) and their haplotypes in the methylenetetrahydrofolate reductase (MTHFR) are associated with NHL, remain inconclusive. We investigated the association between MTHFR C677T and A1298C SNPs and NHL risk in a population which is made up of Malay, Chinese and Indian ethnic subgroups. A total of 372 NHL patients and 722 controls were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects failed to demonstrate significant association between the MTHFR C677T and A1298C SNPs with NHL and its subtypes. The results were in agreement with the previous meta-analyses. In the Indian ethnic subgroup however, single locus analysis of MTHFR A1298C appears to confer risk to NHL (Odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.22-3.00, P=0.006). The risk is almost doubled in homozygous carrier of MTHFR 1298CC (OR 4.03, 95% CI 1.56-10.43, P=0.004). Haplotype analysis revealed higher frequency of CC in the Indian NHL patients compared with controls (OR 1.86, 95% CI 1.18-2.93, P=0.007). There is lack of evidence to suggest an association between MTHFR C677T and A1298C with the risk of NHL in the Malays and Chinese. In the Indians however, the MTHFR A1298C confers risk to NHL. This study suggests ethnicity modifies the relationship between polymorphisms in the folate-metabolizing gene and NHL.
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Suthandiram
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Gin Gin
authors.initials: GG
authors.lastname: Gan
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shamsul Mohd
authors.initials: SM
authors.lastname: Zain
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Batoul Sadat
authors.initials: BS
authors.lastname: Haerian
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ping Chong
authors.initials: PC
authors.lastname: Bee
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lay Hoong
authors.initials: LH
authors.lastname: Lian
authors.affiliation: Department of Hematology, Ampang Hospital, Selangor Darul Ehsan, Malaysia.
authors.forename: Kian Meng
authors.initials: KM
authors.lastname: Chang
authors.affiliation: Department of Hematology, Ampang Hospital, Selangor Darul Ehsan, Malaysia.
authors.forename: Tee Chuan
authors.initials: TC
authors.lastname: Ong
authors.affiliation: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)