Abstract
A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420T polymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a more precise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 available studies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significant association between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer, gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associated with decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838, 95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysis was performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverse association was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for the PB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association was only found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggest that SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decrease cancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis.
Highlights
Cancer is a major public health problem all over the world
Stratifying by geographic area (America, Asia and Europe), significant inverse association was only found in Asia subgroup (CT vs. CC: odds ratios (ORs)= 0.674, 95% confidence intervals (95% CIs) = 0.522-0.870)
Stratifying by geographic area, significant inverse association was only found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870)
Summary
In the United States, one in four deaths is due to cancer (Siegel et al, 2013). It has been suggested that susceptibility genes combining with environmental factors may be important in the development of cancer (Lichtenstein et al, 2000). Epidemiologic studies indicate that folate metabolism imbalance can lead to reduced S-adenosylmethionine (SAM) production and modification of DNA methylation profile promoting stimulation of protooncogene and inactivation of tumor growth suppressor genes. Serine hydroxymethyltransferase (SHMT) is a key enzyme controlling folate metabolism. It catalyzes the reversible conversion of serine and tetrahydrofolate (THF) to glycine and methylene THF to provide one-carbon units for the synthesis of SAM, purine, and thymidine. SHMT1 is one of SHMT isoenzymes, which plays a crucial role in generating one-carbon units for purine, thymidylate, and methionine synthesis in the cytoplasm (Girgis et al, 1997).
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