Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma.
Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma.
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发表时间：
2003
期刊：
影响因子：
10.1
通讯作者：
A. Hishida;K. Matsuo;N. Hamajima;Hidemi Ito;M. Ogura;Y. Kagami;H. Taji;Y. Morishima;N. Emi;K. Tajima
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作者：
A. Hishida;K. Matsuo;N. Hamajima;Hidemi Ito;M. Ogura;Y. Kagami;H. Taji;Y. Morishima;N. Emi;K. Tajima
胸苷酸合成酶（TS）启动子区28-bp串联重复序列和胞质丝氨酸羟甲基转移酶（SHMT 1 C1420 T）的多态性已被报道可调节成人急性淋巴细胞白血病（ALL）的风险。我们研究了恶性淋巴瘤易感性与这些多态性之间的关系。设计与方法在爱知县癌症中心进行以医院为基础的流行病例对照研究。评估了108例组织学确诊的淋巴瘤患者和494例非癌症对照组。结果：在对每种基因型的风险评估中，携带至少一个TS 2重复（2 R）等位基因的人患恶性淋巴瘤的风险增加了1.6倍（OR=1.63; 95%CI，1.05-2.53，p=0.030）。对于SHMT 1 C1420 T多态性，那些携带至少一个T等位基因的人显示风险降低2.2倍（OR =0.46; 95%CI，0.23-0.93，p=0.031）。此外，TS和SHMT 1多态性的联合分析显示，SHMT 1 1420 CC和TS 2 R等位基因的患者患淋巴瘤的OR为2.88（95% CI，1.26-6.58，p=0.013），这可能是预期提供最高易感性的基础。解释和结论本研究提示叶酸代谢基因低多态性的遗传特征可能调节恶性淋巴瘤的风险。
BACKGROUND AND OBJECTIVES 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. DESIGN AND 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). INTERPRETATIONS AND CONCLUSIONS This study suggests that genetic traits involving low penetrance polymorphisms in folate-metabolizing genes may modulate the risk of malignant lymphoma.