Polymorphism of cytosolic serine hydroxymethyltransferase and breast cancer risk: evidence from a meta-analysis.

One-carbon metabolism has been presumed to influence cancer pathogenesis. Cytosolic serine hydroxymethyltransferase (cSHMT) is a critical enzyme in one-carbon metabolism pathway. Until now, many studies have investigated the association between cSHMT (also named SHMT1) C1420T polymorphism and breast cancer risk. However, the results remained conflicting rather than conclusive. Literature search was conducted using PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases until December 2013 to identify studies investigating the association of SHMT1 C1420T polymorphism with breast cancer risk. The strength of the association was assessed by the summary odd ratios (ORs) and their corresponding 95 % confidence interval (CI). Seven studies with a total of 5,534 cases and 6,581 controls were included. Overall, no association was detected between SHMT1 C1420T polymorphism and breast cancer risk (T vs. C, OR = 0.97, 95 % CI = 0.92-1.03). In the subgroup analysis based on ethnicity, SHMT1 C1420T polymorphism has shown a protective effect on breast cancer in Asians (T vs. C, OR = 0.78, 95 % CI = 0.66-0.93) but not in Caucasian (T/T vs. C/C, OR = 0.98, 95 % CI = 0.86-1.12). Significant heterogeneity across studies could be observed in some genetic comparison models in the overall estimation (C/T vs. C/C, P het = 0.004; T/T+C/T vs. C/C, P het = 0.006) but turned to be mild in all comparison models when stratified by ethnicity. Our meta-analysis failed to detect association between SHMT1 C1420T polymorphism and breast cancer risk. However, we found evidence for association of SHMT1 C1420T polymorphism with significantly reduced risk of breast cancer in Asians. Further well-designed studies with larger sample size and better selected controls are warranted.