Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma.
OBJECTIVE
Polymorphisms in thymidylate synthase (TS) 28-bp tandem repeats in the promoter region and in cytosolic serine hydroxymethyltransferase (SHMT1 C1420T) have been reported to modulate the risk of adult acute lymphocytic leukemia (ALL). We examined the associations between susceptibility to malignant lymphoma and these polymorphisms.


METHODS
A hospital-based prevalent case-control study was conducted in Aichi Cancer Center. One hundred and eight patients with histologically confirmed lymphoma and 494 control subjects without cancer were evaluated.


RESULTS
In a risk estimation of each genotype, those who harbored at least one TS 2 repeat (2R) allele had a 1.6-fold increase in the risk of malignant lymphoma (OR=1.63; 95%CI, 1.05-2.53, p=0.030) when using those without the TS 2R allele as a reference. For the SHMT1 C1420T polymorphism, those harboring at least one T allele showed a 2.2-fold decrease in risk (OR =0.46; 95% CI, 0.23-0.93, p=0.031). Moreover, combined analysis of TS and SHMT1 polymorphisms revealed that the OR for lymphoma in patients with SHMT1 1420 CC and the TS 2R allele, which might be expected to provide the basis for the highest susceptibility, was 2.88 (95% CI, 1.26-6.58, p=0.013).


CONCLUSIONS
This study suggests that genetic traits involving low penetrance polymorphisms in folate-metabolizing genes may modulate the risk of malignant lymphoma.
Hishida
Asahi
A
Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan. a-hishi@med.nagoya-u.ac.jp
Matsuo
Keitaro
K
Hamajima
Nobuyuki
N
Ito
Hidemi
H
Ogura
Michinori
M
Kagami
Yoshitoyo
Y
Taji
Hirofumi
H
Morishima
Yasuo
Y
Emi
Nobuhiko
N
Tajima
Kazuo
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D008223:Lymphoma / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013940:Thymidylate Synthase / Q000235:genetics*
D005492:Folic Acid; D013940:Thymidylate Synthase; D012696:Glycine Hydroxymethyltransferase