Variations in the MHC region confer risk to esophageal squamous cell carcinoma on the subjects from high-incidence area in northern China.

BACKGROUND: The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population. METHODS: Conditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues. RESULTS: Of the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (P = 6.07E-06, OR = 1.71, 95%CI = 1.36-2.17), rs3763338 (P = 1.62E-05, OR = 0.63, 95%CI = 0.50-0.78) and rs2844695 (P = 7.60E-05, OR = 0.74, 95%CI = 0.64-0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (P = 0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (P = 0.001) and family history (P<0.001). CONCLUSION: This study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.

Effect of elemental nano-selenium on semen quality, glutathione peroxidase activity, and testis ultrastructure in male Boer goats.

The objective of this experiment is to study the effects of novel elemental nano-selenium in the diet on testicular ultrastructure, semen quality and GSH-Px activity in male goats. Forty-two 2-month-old bucks were offered a total mixed ration which had been supplemented with nano-Se (0.3mg/kg Se) or unsupplemented (the control group only received 0.06mg/kg Se-background), for a period of 12 weeks (from weaning to sexual maturity). Results showed that the testicular Se level, semen glutathione peroxidase and ATPase activity increased significantly in the nano-Se supplementation group compared with control (P<0.05). The semen quality (volume, density, motility and pH) was not affected by added Se in diets, however, the sperm abnormality rate of control bucks was significantly higher than Se supplemented bucks (P<0.05). The testes of 5 goats in each group were examined by transmission electron microscopy (TEM), and showed that in Se-deficient bucks the membrane was damaged, and showed the occurrence of abnormalities in the mitochondria of the midpiece of spermatozoa. In conclusion, selenium deficiency resulted in abnormal spermatozoal mitochondria, and supplementation with nano-Se enhanced the testis Se content, testicular and semen GSH-Px activity, protected the membrane system integrity and the tight arrayment of the midpiece of the mitochondria. Further studies are required to research the novel elemental nano-Se with characterization of bioavailability and toxicity in small ruminants.