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Previous studies suggested that alterations in the energy metabolism might be underlying cancer initiation and progression. Polymorphisms of genes involved in energy metabolism regulation, such as peroxisome proliferator-activated receptor gamma coactivator 1α (PPARGC1A), -β (PPARGC1B), and paraoxonase 1 (PON1), might confer susceptibility to esophageal squamous cell carcinoma (ESCC) and partially explain its pathogenesis. We investigated the effects of several single nucleotide polymorphisms (SNPs) in three metabolic-related genes (e.g., PPARGC1A, PPARGC1B, and PON1) on ESCC susceptibility. In total, 829 patients with sporadic ESCC and 1522 nontumor controls were enrolled in the study. SNPs were genotyped using PCR-ligase detection reaction. Our study revealed that the PPARGC1A rs3736265 G/A SNP significantly increased the risk for ESCC (GA vs. GG: adjusted odds ratio [OR] = 1.25, 95% confidence interval [95% CI] = 1.02–1.54, p = 0.034; GA+AA vs. GG: adjusted OR = 1.25, 95% CI = 1.03–1.52, p = 0.027]. In addition, a stratified analysis revealed that the PPARGC1A rs3736265 SNP was correlated with the development of ESCC in male and nondrinking subgroups. We also confirmed that the PPARGC1B rs17572019 G/A SNP promoted the risk of ESCC in subgroup with high alcohol intake. The PPARGC1A rs8192678 C/T polymorphism decreased the susceptibility of ESCC in men. These findings highlight that polymorphisms in PPARGC1A and PPARGC1B may contribute to ESCC susceptibility. In the future, further well-designed epidemiological studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

microRNAs' (miRNAs) loci may influence hepatocellular carcinoma (HCC) development. Many recent studies have assessed the relationship between miRNA-499, miRNA-146a, and miRNA-196a2 loci and HCC risk. However, the observed results are conflicting. A total of 584 HCC patients and 923 age- and sex-matched controls were recruited. The correlation of miRNA-499 rs3746444, miRNA-146a rs2910164, and miRNA-196a2 rs11614913 with HCC development was assessed. In the <53-year-old subgroup, a correlation of the rs2910164 locus with HCC risk was found (GG/CG vs. CC: adjusted p = 0.011, GG vs. CC: adjusted p = 0.021 and CG vs. CC: adjusted p = 0.027). The association between miRNA-146a rs2910164 and the risk of HCC was also found in the never smoking (GG/CG vs. CC: adjusted p = 0.011 and CG vs. CC: adjusted p = 0.018). Using false-positive report probability method and power value, we identified that miRNA-146a rs2910164 conferred a risk to HCC in the <53-year-old and never-smoking subgroups. In conclusion, this study indicates rs2910164 may be a risk factor for HCC, especially in the <53-year-old and never-smoking subgroups. [ABSTRACT FROM AUTHOR]

Tumor antigen-induced lymphocyte transformation (LT) represents the antitumor cellular immunity, which might correlate with the cancer treatment outcome. Currently, there is no LT assay (LTA) routinely used in clinic. To establish a sensitive and convenient procedure for LTA, the same samples were used to simultaneously perform three assays: 5-ethynyl-2′-deoxyuridine (EdU) assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and carboxyfluorescein succinimidyl ester (CFSE) assay, and then the three results were compared. Several conditions were optimized: the LT harvest time, sources of lymphocytes (blood, lymph nodes, or spleen), the added amount of stimulatory tumor antigen and in vivo immunization priming time for LTA. The results of side-by-side comparison showed that (1) the 72 h for coculture of lymphocytes with tumor antigens was optimal time to harvest cells for LTA; (2) 50 μg/mL of tumor antigens was the optimal concentration for activation LT from three sources; (3) EdU incorporation was the sensitive and convenient assay for LTA as compared with MTT and CFSE assays; (4) the day 21–28 after in vivo priming immunization was the testing time for LTA; and (5) peripheral blood LT could be a good representative of whole body's lymphocyte reaction and practically easy cell source for LTA. This comparison of the three LTA in mouse model suggests that the EdU incorporation assay might be useful to evaluate the antitumor immunity stimulated by specific tumor vaccine or different anticancer therapies. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a key negative immunoregulatory molecule with characteristics of gene polymorphisms. Genetically predisposed CTLA-4 alteration in humans was associated with gastric cancer (GC) development. To explore the association of CTLA-4 polymorphism with susceptibility of noncardiac GC (NCGC), 490 NCGC patients and 1476 control individuals were studied. Four CTLA-4 polymorphisms were genotyped with SNPscan genotyping assays and the haplotypes were constructed with SHESIS software. Frequencies of the CTLA-4 haplotypes were estimated using an expectation–maximization algorithm. The CTLA-4 polymorphism genotype distribution and allele frequencies were not significantly different between the NCGC patients and the control subjects. The CTLA-4 haplotypes did not exhibit a significantly increased risk for NCGC patients. Adjusting status of age, sex, smoking status, alcohol use, and body mass index could not moderate any of the relationships. Data suggested that CTLA-4 polymorphisms (rs3087243, rs16840252, rs733618, and rs231775) were not significantly associated with the risk of NCGC in this Chinese population studied. [ABSTRACT FROM AUTHOR]