Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies.

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.

Prevalence of human papillomavirus infection in esophageal and cervical cancers in the high incidence area for the two diseases from 2007 to 2009 in Linzhou of Henan Province, Northern China.

The etiological role of human papillomavirus (HPV) in cervical cancer has been well established. However, it is inconclusive whether HPV plays the same role in esophageal carcinogenesis. In this study, we detected HPV infection in 145 frozen esophageal tissues, including 30 normal epithelium (ENOR), 37 dysplasia (DYS) and 78 invasive squamous cell carcinoma (ESCC), and in 143 frozen cervical tissues composed of 30 normal epithelium (CNOR), 38 intraepithelial neoplasia (CIN) and 75 invasive squamous cell carcinoma (CSCC). The patients and symptom-free subjects enrolled in this study were from a high-incidence area for both ESCC and CSCC, Linzhou City, Northern China, from 2007 to 2009. The HPV infection analysis was conducted by using an HPV GenoArray Test Kit. We found that the high-risk HPV types accounted for more than 90 % of the HPV-positive lesions of esophagus and cervix tissues. The prevalence of high-risk HPV types increased significantly during the progression of both esophageal and cervical carcinogenesis (positive rate in esophageal tissues: 33 % ENOR, 70 % in DYS and 69 % in ESCC; positive rate in cervical tissues: 27 % in CNOR, 82 % in CIN and 88 % in CSCC; P < 0.001, respectively). Infection with the high-risk HPV types increased the risk for both DYS and ESCC by 4-fold (DYS vs. ENOR: OR = 4.73, 95 %CI = 1.68-13.32; ESCC vs. ENOR: OR = 4.50, 95 %CI = 1.83-11.05) and increased the risk for both CIN and CSCC by 12-fold and 20-fold (CIN vs. CNOR: OR = 12.18, 95 %CI = 3.85-38.55; CSCC vs. CNOR: OR = 20.17, 95 %CI = 6.93-58.65), respectively. The prevalence of high-risk types in ESCC patients was lower than that in CSCC patients (P = 0.005) and was significantly associated with the degree of ESCC tumor infiltration (P = 0.001). HPV 16 was the most prevalent subtype in both esophageal and cervical tissues. Single HPV infection increased significantly along with the progression of ESCC and maintained a high level in cervical tissues, regardless of whether they were CNOR or CSCC tissues. Our results showed that infection with HPV, especially the high-risk types, was positively associated with both esophageal and cervical cancers, suggesting that HPV also plays a role in the etiology of ESCC in the high-incidence area.

Increasing CCL5/CCR5 on CD4+ T cells in peripheral blood of oral lichen planus.

Oral lichen planus (OLP) is a T cell-mediated autoimmune disease of oral mucosa, in which T helper 1 (Th1) cells are greatly involved. Chemokine CCL5 is required for T cells infiltration and activation. CCR5, one of its receptors, specifically expressed on Th1 cells among CD4(+) T cells, can be up-regulated by Th1 cytokines like interleukin2 (IL-2) and interferon-gamma (IFN-γ), and down-regulated by Th2 cytokines like IL-4. The present study aimed to determine whether CCL5 and CCR5 had effects on the immune response of OLP. We analyzed the proportion of CCR5(+)CD4(+) T cells in CD4(+) T cells using flow cytometry and the serum levels of CCL5, IL-2, IFN-γ, and IL-4 with ELISA. MicroRNA-125a (miR-125a), a blocker of CCL5, was examined with RT-PCR. The results showed both the serum CCL5 and the percentage of CCR5(+)CD4(+) T cells elevated in OLP patients. Serum IL-2 and IFN-γ increased in OLP patients, but IL-4 decreased. MiR-125a was down-regulated in OLP patients, and there was a negative correlation between miR-125a content and the OLP severity which was measured with a RAE (reticular, atrophic and erosive lesion) scoring system. In conclusion, increasing CCl5/CCR5 might participate in the immune response of OLP. Th1-type cytokines environment presented in OLP probably performed as a magnifier for the CCR5. Moreover, miR-125a might be a candidate biomarker to estimate the severity of OLP.

[Oral candida species distribution in patients receiving radiotherapy for head and neck cancer].

PURPOSE: To investigate the distribution of oral candida species in head and neck cancer (HNC) patients treated with radiation therapy, and provide the basis for planning of clinical preventive measures. METHODS: Saliva was sampled from 60 HNC patients before, during and after radiation. Concomitantly, 60 healthy individuals whose age and sex matched that of the patient group were selected as control group. Oral candida carriages were quantitatively detected and the different candida species were identified by multiple measures such as CHROMagar candida culture medium and API 20C AUX yeast identification system. Then the differences between the two groups in terms of the candida detection rate and the distribution of each species of candida were analyzed with SPSS 17.0 software package. RESULTS: Xerostomia and dysphagia was found in 54 HNC patients during radiotherapy, radiation-induced oral mucotitis(RIOM) was found in 50 HNC patients,and oral candidiasis was found in 18 HNC patients; In radiation group, the detection rate of candida colonization during radiation was 56.7%, 63.3% postradiation, which showed significant differences compared with pre-radiation (X² =18.320,P<0.001 ); Among the 54 identified clinical isolates, candida albicans (n=42) was the most frequent, followed by candida parapsilosis (n=6), candida tropicalis (n=4) and candida glabrata (n=2). In radiation group, the oral candida pathogens detection rate was 30%, and candida colonization was 46.7%. CONCLUSIONS: The oral candida colonization rate was significantly higher in HNC patients after radiotherapy, which indicated that the candida infection may be closely related to RIOM.

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.