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Background: Cancers from lung and esophagus are the leading causes of cancer-related deaths in China and share many similarities in terms of histological type, risk factors and genetic variants. Recent genome-wide association studies (GWAS) in Chinese esophageal cancer patients have demonstrated six high-risk candidate single nucleotide polymorphisms (SNPs). Thus, the present study aimed to determine the risk of these SNPs predisposing to lung cancer in Chinese population. Methods: A total of 1170 lung cancer patients and 1530 normal subjects were enrolled in this study from high-incidence areas for esophageal cancer in Henan, northern China. Five milliliters of blood were collected from all subjects for genotyping. Genotyping of 20 high-risk SNP loci identified from genome-wide association studies (GWAS) on esophageal, lung and gastric cancers was performed using TaqMan allelic discrimination assays. Polymorphisms were examined for deviation from Hardy-Weinberg equilibrium (HWE) using Х2 test. Bonferroni correction was performed to correct the statistical significance of 20 SNPs with the risk of lung cancer. The Pearson’s Х2 test was used to compare the distributions of gender, TNM stage, histopathological type, smoking and family history by lung susceptibility genotypes. Kaplan-Meier and Cox regression analyses were carried out to evaluate the associations between genetic variants and overall survival. Results: Four of the 20 SNPs identified as high-risk SNPs in Chinese esophageal cancer showed increased risk for Chinese lung cancer, which included rs3769823 (OR = 1.26; 95% CI = 1.107–1.509; P = 0.02), rs10931936 (OR = 1.283; 95% CI = 1.100–1.495; P = 0.04), rs2244438 (OR = 1.294; 95% CI = 1.098–1.525; P = 0.04) and rs13016963 (OR = 1.268; 95% CI = 1.089–1.447; P = 0.04). All these SNPs were located at 2q33 region harboringgenes of CASP8, ALS2CR12 and TRAK2. However, none of these susceptibility SNPs was observed to be significantly associated with gender, TNM stage, histopathological type, smoking, family history and overall survival. Conclusions: The present study identified four high-risk SNPs at 2q33 locus for Chinese lung cancer and demonstrated the shared susceptibility loci at 2q33 region for Chinese lung and esophageal cancers. [ABSTRACT FROM AUTHOR]

Background: Our previous genome-wide association study (GWAS) identified three independent single nucleotide polymorphisms (SNPs) in human major histocompatibility complex (MHC) region showing association with esophageal squamous cell carcinoma (ESCC). In this study, we increased GWAS sample size on MHC region and performed validation in an independent ESCC cases and normal controls with aim to find additional loci at MHC region showing association with an increased risk to ESCC. Methods: The 1,077 ESCC cases and 1,733 controls were genotyped using Illumina Human 610-Quad Bead Chip, and 451 cases and 374 controls were genotyped using Illumina Human 660W-Quad Bead Chip. After quality control, the selected SNPs were replicated by TaqMan genotyping assay on another 2,026 ESCC cases and 2,384 normal controls. Results: By excluding low quality SNPs in primary GWAS screening, we selected 2,533 SNPs in MHC region for association analysis, and identified 5 SNPs with p <10−4. Further validation analysis in an independent case-control cohort confirmed one of the 5 SNPs (rs911178) that showed significant association with ESCC. rs911178 (PGWAS = 6.125E-04, OR = 0.644 and Preplication = 1.406E-22, OR = 0.489) was located at upstream of SCAND3. Conclusion: The rs911178 (SCAND3 gene) in MHC region is significantly associated with high risk of ESCC. This study not only reveal the potential role of MHC region for the pathogenesis of ESCC, but also provides important clues for the establishment of tools and methods for screening high risk population of ESCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the most important factors affecting the prognosis of the patients with squamous cell carcinoma (SCC) of the larynx. Methods: Based on the clinical and follow-up data, 205 patients with SCC of the larynx receiving total laryngectomy, partial laryngectomy, or CO2 laser surgery in GuangDong General Hospital were retrospectively analyzed. A survival analysis was performed by the Kaplan-Meier method and a multivariable analysis of prognostic factors was carried out using the Cox proportional hazard model. Results: Subtypes of carcinoma included 69.8% glottic and 30.2% supraglottic. Most patients were in N0 stage (77.6%), and 22.4% patients were in N1∼N3 stage. Over half of the patients were in T1∼T2 stage (55.1%), 20.0% in T3, and 24.9% in T4. Mean follow-up duration was 49.2 months. The survival rates 1, 2, and 3 years after the surgery were 99.0%, 91.7%, and 81.5%, respectively. The survival rate for those patients with clinical stage IV was significantly lower than for those with clinical stage I and II (p<0.001 and p = 0.013, respectively). The disease-free progression rates 1, 2, and 3 years after the surgery were 83.9%, 74.6%, and 71.2%, respectively. Futhermore, those patients with a Charlson score of 1 to 2 and ≥3 had higher risk of mortality than those with a Charlson score of 0 (hazard ratios of 1.8 and 2.41 p = 0.042 and p = 0.008). Multivariable analysis revealed that clinical stage, surgical margin, and comorbidity were significantly associated with both mortality and disease-free progression. Conclusion: The surgical resection margin, clinical stage, and comorbidity were independent factors affecting the laryngeal cancer prognosis. The survival rates were lower for patients with advanced laryngeal cancer, positive surgical margins, or severe comorbidity, suggesting the importance of early diagnosis, early treatment, negative surgical margins, and conditions of comorbidity. [ABSTRACT FROM AUTHOR]