Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.
Aged ; Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; Databases, Genetic ; Esophageal Squamous Cell Carcinoma ; genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Internet ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; User-Computer Interface

OBJECTIVETo investigate the association between the rs2274223 and rs3765524 polymorphism of phospholipase C epsilon 1 (PLCE1) gene and the susceptibility to develop esophageal squamous cell carcinoma (ESCC) in a pure Kazakh Chinese population.

METHODSMatrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was utilized to genotype the potentially functional single nucleotide polymorphism rs2274223 A>G and rs3765524 C>T of PLCE1 in an ongoing hospital-based and case-control study of 200 ESCC cases with 300 cancer-free age ( ± 5 years) and sex matched controls. Statistical analyses were performed with Statistical Products and Services Solutions software (version 13.0). Adjusted odds ratios (OR) and 95% confidence evaluation intervals (95%CI) measured by multivariate logistic regression analysis were adopted to study the correlation of the gene polymorphism with the susceptibility to ESCC.

RESULTSThe genotype frequencies observed for rs2274223 was consistent with Hardy-Weinberg equilibrium in controls. Univariate analysis revealed significant differences between cases and controls with respect to genotype distribution for rs2274223 (P = 0.006). The variants of rs2274223 were found to confer significantly increased risk of ESCC (GG vs AA: OR = 3.17, 95%CI = 1.45-6.93; AG/GG vs AA: OR = 1.55, 95%CI = 1.08-2.22) in the Kazakh Chinese population. Moreover, AG/GG genotype of rs2274223 was found to be significantly associated with poorly-differentiated ESCC (OR = 2.48, 95%CI = 1.10-5.60). When the ESCC patients were divided into two subgroups, stage I/II and stage III/IV according to the AJCC TNM classification, the GT/GG genotype of rs2274223 was significantly associated with stage III/IV ESCC (OR = 1.85, 95%CI = 1.05-3.25). No significant association was found between rs3765524 and Kazakh ESCC.

CONCLUSIONSThese results indicate that rs2274223 site polymorphism of the PLCE1 gene is strongly associated with risk of ESCC in a Kazakh Chinese population, especially the poorly-differentiated and stage III/IV ESCC.

Alleles ; Carcinoma, Squamous Cell ; ethnology ; genetics ; Case-Control Studies ; China ; epidemiology ; Confidence Intervals ; Esophageal Neoplasms ; ethnology ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Kazakhstan ; ethnology ; Male ; Middle Aged ; Odds Ratio ; Phosphoinositide Phospholipase C ; genetics ; Polymorphism, Single Nucleotide ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

BACKGROUNDIn China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.

METHODSThe percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.

RESULTSA positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P < 0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P < 0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P < 0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P < 0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age ≥ 50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.

CONCLUSIONSThe proportion of familial cancer in upper gastrointestinal carcinomas decreases by the primary site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

Adenocarcinoma ; genetics ; Age of Onset ; Carcinoma, Squamous Cell ; genetics ; Cardia ; China ; Esophageal Neoplasms ; genetics ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; epidemiology ; Risk Factors ; Stomach Neoplasms ; genetics

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.
Adenocarcinoma ; ethnology ; etiology ; genetics ; Alcohol Drinking ; adverse effects ; Asia ; epidemiology ; Asian Continental Ancestry Group ; genetics ; Carcinoma, Squamous Cell ; ethnology ; etiology ; genetics ; Esophageal Neoplasms ; ethnology ; etiology ; genetics ; European Continental Ancestry Group ; genetics ; Gastroesophageal Reflux ; complications ; Genetic Predisposition to Disease ; Humans ; Incidence ; Obesity ; complications ; Polymorphism, Single Nucleotide ; Risk Factors ; Smoking ; adverse effects ; United States ; epidemiology

Oncologists and scientists in the field of head and neck cancer exchanged their research findings and clinical experiences in the Sino-USA Symposium on Head and Neck Cancer, which was held January 6-7, 2012 in Guangzhou, China. The symposium was jointly organized by Sun Yat-sen University Cancer Center (SYSUCC) and the University of Texas MD Anderson Cancer Center (MDACC). The Guangdong Provincial Anti-Cancer Association and the Chinese Journal of Cancer also helped in organizing the conference. Speakers were from China (SYSUCC, the Chinese University of Hong Kong, Tianjin Medical University Cancer Institute and Hospital, and Fudan University Shanghai Cancer Center) and the United States (MDACC). The presentations covered most kinds of head and neck cancers and included both basic and clinical research progress. In particular, NPC was discussed in depth. The symposium explored the reality that cancer is complex and numerous questions remain to be answered, even though there has already been an enormous effort into research. International exchanges of experience and in-depth cooperation are definitely needed to improve our capability of caring for cancer patients. In this article, we provide highlights of the presentations.
Carcinoma, Squamous Cell ; genetics ; Combined Modality Therapy ; Drug Delivery Systems ; Head and Neck Neoplasms ; drug therapy ; etiology ; genetics ; pathology ; surgery ; Humans ; Nasopharyngeal Neoplasms ; genetics ; pathology ; therapy ; Thyroid Neoplasms ; epidemiology

OBJECTIVEThis study aimed to explore the roles of three common single nucleotide polymorphisms in the X-ray repair cross-complementing group-1 gene (XRCC1) and of life style factors and their possible interactions in the risk of esophageal squamous cell carcinoma (ESCC) in China.

METHODSA population-based case-control study of 432 cases and 915 controls was conducted in Yangzhong County, Jiangsu Province, China. Subjects were interviewed by trained interviewers using a structured questionnaire that included questions on demographics and life style. XRCC1 genotypes were analyzed using a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay. Unconditional logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations of ESCC with XRCC1 polymorphisms and lifestyle-related factors.

RESULTSBoth the drinking of river water and alcohol intake history were significantly associated [SW1]with an increased risk of ESCC among men with aORs of 4.20 (95% CI: 2.90-6.07) and 2.03 (95% CI: 1.43-2.89), respectively. For women, the corresponding odds ratios were 8.37 (95% CI: 5.09-13.75) for river water drinking and 12.78 (95% CI: 2.69-60.69) for long-term stored rice intake. After the XRCC1 G28152A polymorphism was adjusted for potential confounders, subjects with GA and AA genotypes had an increased risk for ESCC (aOR: 1.21, 95% CI: 0.93-1.56), compared with subjects with a GG genotype, and a positive multiplicative interaction between intake of long-term stored rice and the XRCC1 G28152A polymorphism was observed (P=0.009).

CONCLUSIONSOur findings suggest that both lifestyle-related factors, including drinking river water, long-term stored rice and alcohol intake, and the XRCC1 G28152A polymorphism were possible risk factors for ESCC, and that the XRCC1 G28152A polymorphism modified the effect of long-term stored rice intake on the risk of ESCC among Chinese people.

Aged ; Carcinoma, Squamous Cell ; epidemiology ; genetics ; Case-Control Studies ; DNA-Binding Proteins ; genetics ; Esophageal Neoplasms ; epidemiology ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Oryza ; Polymorphism, Genetic ; genetics ; X-ray Repair Cross Complementing Protein 1

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.
Adenocarcinoma ; pathology ; Biomarkers, Tumor ; analysis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; radiotherapy ; Carcinoma, Small Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Chromosome Deletion ; DNA Damage ; Genes, Tumor Suppressor ; Humans ; Incidence ; Lung Neoplasms ; diagnosis ; epidemiology ; etiology ; genetics ; Neoplasms, Multiple Primary ; diagnosis ; epidemiology ; etiology ; genetics ; Smoking ; adverse effects

The GSTP1 and NQO1 have been reported to be associated with an increased risk for smoking related head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to determine the effect of these metabolic gene polymorphisms on the risk of HNSCC. The study population included 294 histologically confirmed HNSCC cases and 333 controls without cancer. Genotyping analysis of the GSTP1 Ile105Val and NQO1 Trp139Arg genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. The Mantel-Haenszel chi-square test was used for statistical analysis. The allele frequencies of the GSTP1 and NQO1 polymorphisms were not statistically significant between cases and controls. In analyzing the association between smoking amounts and genetic polymorphisms, GSTP1 and NQO1 polymorphisms were associated with cigarette smoking amounts in cases. G allele containing genotypes in GSTP1 and T allele containing genotypes in NQO1 were associated with a tobacco dose-dependent increase in risk of HNSCC and these genotype distributions were statistically significant (p<0.05). We found that the GSTP1 105Val allele and NQO1 139Arg allele were associated with tobacco dose-dependent increase in risk of HNSCC. GSTP1 and NQO1 genotype polymorphisms may play an important role in the development of smoking related HNSCC.
Smoking/*epidemiology ; Risk Factors ; Risk Assessment/methods ; Prevalence ; Polymorphism, Single Nucleotide/genetics ; NAD(P)H Dehydrogenase (Quinone)/*genetics ; Middle Aged ; Male ; Korea/epidemiology ; Humans ; Head and Neck Neoplasms/*epidemiology/*genetics ; Glutathione S-Transferase pi/*genetics ; Genetic Predisposition to Disease/genetics ; DNA Mutational Analysis ; Carcinoma, Squamous Cell/*epidemiology/*genetics ; Aged, 80 and over ; Aged ; Adult

OBJECTIVETo investigate 30 bp deletion of latent membrane protein (LMP)-1 gene in lymphoepithelial carcinoma (LEC) of the salivary glands and to determine the frequency of this deletion.

METHODSForty-six cases of salivary gland LEC were investigated by PCR to explore the site specific, 30 bp deletion in the 3' terminal region of LMP-1 gene. To guarantee amplifiable DNA extracted from paraffin-embedded tissue sections, PCR amplification of a house-keeping gene (beta-actin) was performed simultaneously. In addition, DNA sequencing of the PCR product was performed in representative cases.

RESULTSAlthough amplifiable DNA was obtained in 42 of the 46 specimens, as indicated by beta-actin gene amplification, successful amplification of LMP-1 gene was achieved in 35/42 (83.3%) cases. Two types of PCR products of LMP-1 gene were observed and confirmed by DNA sequencing. A wild-type PCR product (316 bp) was present in 31 cases (88.6%) and only 4 cases (11.4%) showed an aberrant 286 bp PCR product, corresponding to the 3' terminal 30 bp deletion of the gene.

CONCLUSIONSite-specific 30 bp deletion of LMP-1 gene is not a common feature of salivary gland LEC.

Base Sequence ; Carcinoma ; genetics ; pathology ; virology ; Carcinoma, Squamous Cell ; genetics ; pathology ; virology ; Epstein-Barr Virus Infections ; epidemiology ; virology ; Gene Deletion ; Herpesvirus 4, Human ; genetics ; Humans ; Molecular Sequence Data ; Oncogene Proteins, Viral ; genetics ; Salivary Gland Neoplasms ; genetics ; pathology ; virology ; Sequence Deletion ; Viral Matrix Proteins ; genetics

OBJECTIVETo characterize the profiles of chromosome imbalance in esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA) from the high incidence area in Henan.

METHODSChromosomal aberrations of 37 samples of SCC and 30 GCA were analyzed by comparative genomic hybridization comparative genomic hybridization (CGH).

RESULTSIt was found that the most frequently detected gains were on chromosome arm 8q (78%), and followed by 3q, 5p, 6q and 7p. The most frequent loss was found on 3p (57%), and followed by 8p, 9q and 11q in SCC. For GCA, the most frequent gain was found on chromosome arm 20q (43%), and followed by 6q, 8q and 6p. The most frequent loss was on the chromosome 17p (57%), and followed by 19p, 1p and 4p.

CONCLUSIONThe present findings demonstrate that gains of 8q, 3q and 5p, and losses of 3p, 8p, and 9q are characteristic profile of chromosome imbalance in SCC, and the gains of 20q, 6q and losses of 17p, 19p and 1p are characteristic profile of chromosome imbalance in GCA, which provide important theoretic information for identifying and cloning novel SCC/GCA-related genes.

Adenocarcinoma ; genetics ; Carcinoma, Squamous Cell ; epidemiology ; genetics ; Cardia ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 20 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 8 ; DNA, Neoplasm ; genetics ; Esophageal Neoplasms ; epidemiology ; genetics ; Gene Amplification ; Gene Deletion ; Humans ; Nucleic Acid Hybridization ; methods ; Stomach Neoplasms ; epidemiology ; genetics