to have an impact on adipogenic differentiation (adipogenesis), lipolysis, and glucose uptake by fat cells [69] and contributes to the formation of MetS [70] and CAD [71]. Further large studies may be needed to elucidate the possible mechanisms of betel quid chewing on the risk of MetS. There are some limitations in this study. First, our data was based on community-dwelling men participating in a free health screening. Although the screening was open to the general male population, some selection bias may have existed. Other large population-based studies may be needed to confirm our preliminary results. Second, this is a cross-sectional study that can only evaluate the possible associations among those factors, MetS and its individual components. However, we can not evaluate the real causal-relationships. Further prospective studies are needed toLow Estradiol and Metabolic Syndromeelucidate the possible effects of those factors on the risk of MetS and its individual components. Third, we did not evaluate the effect of total and free testosterone levels which may play important roles in the risk of MetS and circulating E2 levels via aromatization.large studies are needed to confirm our preliminary results and elucidate the possible mechanism.AcknowledgmentsThe authors thank Ms. Chao-Shih Chen for her help to hold health screening and perform data collection.ConclusionsIn addition to get [DTrp6]-LH-RH adiponectin and leptin, E2 and 1,25(OH)2D3 were significantly associated with the risk of MetS and its individual components in middle-aged males. With increasing numbers of MetS components, there were a linear-shaped decline in 1,25(OH)2D3 and a ladder-shaped decline in E2 levels. FurtherAuthor ContributionsConceived and designed the experiments: KHC SPH CCL. Performed the experiments: KHC SPH CNH YCL CSC WTL CCL. Analyzed the data: KHC SPH CCL. Contributed reagents/materials/analysis tools: KHC SPH CFC CCL. Wrote the paper: KHC.
common male cancer and the sixth leading cause of cancer death in Taiwan [1]. The development of OSCC is a multistep process requiring the accumulation of multiple genetic alterations, affected by a patient’s genetic predisposition and by environmental influences, including 
alcohol and tobacco consumption, betel-quid chewing, chronic inflammation, and viral infection [1?]. Expression of a gene may be affected by a single-nucleotide polymorphism (SNP) located within the promoter or other regulatory regions of the gene, and the production or activity of its translated protein isfurther modulated. SNPs, which are the most common type of DNA sequence variation, occur when a HDAC-IN-3 web single nucleotide in the shared sequence of a gene differs between members of a species or paired chromosomes in an individual, and are thought to be associated with the development of certain diseases [7]. Genotyping-related SNPs might be a simple and valuable method to predict the risk for and prognosis of cancer. To elucidate the complex process of carcinogenesis and improve the scientific basis for preventive interventions, identifying major genes related to the susceptibility for OSCC should be a priority and effecti.Ults. In addition to smoking and alcohol 1516647 drinking, our study also found that subjects with MetS had significantly higher prevalence of betel quid chewing than those without MetS. Arecoline, a major alkaloid in betel nuts, has been reported to have an impact on adipogenic differentiation (adipogenesis), lipolysis, and glucose uptake by fat cells [69] and contributes to the formation of MetS [70] and CAD [71]. Further large studies may be needed to elucidate the possible mechanisms of betel quid chewing on the risk of MetS. There are some limitations in this study. First, our data was based on community-dwelling men participating in a free health screening. Although the screening was open to the general male population, some selection bias may have existed. Other large population-based studies may be needed to confirm our preliminary results. Second, this is a cross-sectional study that can only evaluate the possible associations among those factors, MetS and its individual components. However, we can not evaluate the real causal-relationships. Further prospective studies are needed toLow Estradiol and Metabolic Syndromeelucidate the possible effects of those factors on the risk of MetS and its individual components. Third, we did not evaluate the effect of total and free testosterone levels which may play important roles in the risk of MetS and circulating E2 levels via aromatization.large studies are needed to confirm our 
preliminary results and elucidate the possible mechanism.AcknowledgmentsThe authors thank Ms. Chao-Shih Chen for her help to hold health screening and perform data collection.ConclusionsIn addition to adiponectin and leptin, E2 and 1,25(OH)2D3 were significantly associated with the risk of MetS and its individual components in middle-aged males. With increasing numbers of MetS components, there were a linear-shaped decline in 1,25(OH)2D3 and a ladder-shaped decline in E2 levels. FurtherAuthor ContributionsConceived and designed the experiments: KHC SPH CCL. Performed the experiments: KHC SPH CNH YCL CSC WTL CCL. Analyzed the data: KHC SPH CCL. Contributed reagents/materials/analysis tools: KHC SPH CFC CCL. Wrote the paper: KHC.