Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In 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.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>A 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.</p><p><b>CONCLUSIONS</b>The 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.</p>

A population-based matched case-control study on the risk factors of gastric cardia cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To find the major risk factors associated with gastric cardia cancer.</p><p><b>METHODS</b>We selected five high incidence areas of esophageal cancer and gastric cancer which have cancer registration system, i.e. Cixian and Shexian of Hebei Province, Linxian of Henan Province, Feicheng of Shandong Province and Zhuanghe of Liaoning Province. Fifty newly diagnosed cases of cardiac cancer after January 1, 2008 were selected from each cancer registration database. A uniform questionnaire, which was fully consulted by experts, was used. Population-based 1:3 case-control study was conducted in those areas. The study recruited 250 cases of cardiac cancer and 750 matched controls, which were investigated with the uniform questionnaire. The data were statistically analyzed by fitting-conditional Logistic analysis.</p><p><b>RESULTS</b>Smoking, passive smoking, alcohol drinking, irregular meal, improper dining posture, heavy taste, dried food, pickled food, fried food, hot food, gastrointestinal history, gastroesophageal reflux disease (GERD) can increase the risk of cardiac cancer. To eat more bean and high BMI are protective factors of the single factor logistic analysis. Gastrointestinal history (OR = 42.899), dried food (OR = 5.932), irregular meal (OR = 4.911), hot food (OR = 4.144), pickled food (OR = 3.287), passive smoking (OR = 2.355), and GERD (OR = 1.930) can increase the risk of cardiac cancer, eat more bean (OR = 0.254) and BMI ≥ 25 (OR = 0.492) are protective factors of the mixture factors logistic analysis.</p><p><b>CONCLUSIONS</b>Gastric cardia cancer is caused by environmental risk factors and genetic factors. Health education in high cardiac cancer incidence areas and primary prevention popularized into people's daily life will be beneficial to decreasing the incidence of gastric cardia cancer.</p>

Analysis of risk factors for upper gastrointestinal cancer in China: a multicentric population-based case-control study / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the major risk factors for upper gastrointestinal cancer in high occurrence areas of esophageal and gastric cancer in China.</p><p><b>METHODS</b>Four high occurrence areas of esophageal cancer, namely Cixian and Shexian from Hebei province, Linxian from Henan province, Feicheng from Shandong province, and Zhuanghe from Liaoning province, which is a high occurrence area of gastric cancer, were selected for the study. The newly-diagnosed cases whose date of onset were after January 1st, 2009 were selected from the Cancer Registration Database in each district, and 751 cases diagnosed as cancers in lower segment of esophagus, cardiac and other subsite of stomach were randomly recruited. 2253 matched controls were selected to pair the cases at the ratio of 3:1. The relative information of the study objects were collected from the face-to-face interviews with trained staff by designed questionnaires, and the data was input by EpiData software. Statistic software SPSS 13.0 was applied to conduct both univariate and multivariate logistic regression analysis to evaluate odd ratios (OR) and 95% confident interval (CI).</p><p><b>RESULTS</b>As univariate analysis shown, 66 objects in case group had irregular diet habit; while 90 in control group had (OR = 3.177; 95%CI: 2.127 - 4.745). A higher percentage in case group (83 objects) preferred fried food in comparison with only 214 in control group did (OR = 3.190; 95%CI: 2.061 - 4.927). 369 objects in case group, but only 119 in control group had history of gastrointestinal diseases (OR = 14.660; 95%CI: 11.342 - 18.948). 282 objects in case group had history of gastroesophageal reflux disease (GERD), which was much higher than the percentage in control group (432 objects), with OR = 3.137 (95%CI: 2.546 - 3.864). All the above factors could increase the risk for upper gastrointestinal cancer. 387 objects in case group and 1278 in control group reported they preferred fresh vegetables in daily diet, which was found to be a protective factor (OR = 0.609; 95%CI: 0.473 - 0.785). As multivariate analysis shown, history of gastrointestinal tract diseases (OR = 21.420; 95%CI: 15.484 - 29.632), irregular food diet (OR = 3.097; 95%CI: 1.740 - 5.514), pickled food (OR = 3.005; 95%CI: 1.873 - 4.819), and GERD (OR = 2.261; 95%CI: 1.673 - 3.057) were found to be risk factors for upper gastrointestinal cancer; while frequent fresh-vegetable diet was a protective factor (OR = 0.562; 95%CI: 0.396 - 0.800).</p><p><b>CONCLUSION</b>Irregular lifestyle and unhealthy diet habit could be the major risk factors for upper gastrointestinal cancers among the residents from high occurrence areas of esophageal cancer and gastric cancer in China.</p>

Association of three single nucleotide polymorphisms of the E-cadherin gene with endometriosis in a Chinese population.

Endometriosis, one of the most frequent diseases in gynecology, is a benign but invasive and metastatic disease. The altered expression of E-cadherin may play an important role in developing endometriosis. In this paper, we discuss the association of three single nucleotide polymorphisms (SNPs) on the E-cadherin gene and risk of endometriosis. We examined the genotype frequency of three polymorphisms in 152 endometriosis patients and 189 control women. There was a significant difference in the frequency of the E-cadherin 3'-UTR C --> T genotypes between endometriosis and controls (P = 0.01). The frequency of the C allele in patients (71.1%) was significantly higher than in the controls (63.8%; P = 0.04). When compared with the T/T + T/C genotypes, the C/C genotype had a significantly increased susceptibility to endometriosis, with an adjusted odds ratio of 1.79 (95% confidence interval = 1.17-2.76). No significant difference was found between endometriosis and control women on two polymorphisms (-160 C --> A, -347 G --> GA) at the gene promoter region of E-cadherin. The -160 C --> A and -347 G --> GA polymorphisms displayed linkage disequilibrium (D' = 0.999). The -160 A/-347 GA haplotype was only detected in endometriosis patients (2%). These data show a relation between the E-cadherin 3'-UTR C --> T polymorphism, the -160 A/-347 GA haplotype of two promoter polymorphisms and risk of endometriosis, suggesting a potential role in endometriosis development, at least in North Chinese women.

Establishment of a diagnostic model of serum protein fingerprint pattern for esophageal cancer screening in high incidence area and its clinical value / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the alterations of serum proteomic pattern in esophageal squamous cell carcinoma (ESCC) by SELDI-TOF-MS, to establish a diagnostic model of ESCC screening in high incidence area and investigate its clinical value.</p><p><b>METHODS</b>SELDI-TOF-MS and CM10 proteinChip were used to detect the serum proteomic patterns of 36 cases of ESCC and 38 healthy control subjects in high incidence area. The data were analyzed and a diagnostic model was established by using support vector machine (SVM). The diagnostic model was evaluated by leave-one-out cross validation.</p><p><b>RESULTS</b>At the molecular weight range of 2000 to 20,000, 31 protein peaks were significantly different between ESCC and controls (P < 0.01). A diagnostic model consisting of 4 protein peaks could do the best in diagnosis of ESCC and controls. The accuracy was 85.1%, sensitivity was 86.1%, specificity was 84.2%, and positive value was 83.8%.</p><p><b>CONCLUSION</b>The diagnostic model formed by 4 protein peaks, established in this study, can well distinguish ESCC from healthy subjects. It provides a new approach for ESCC screening in high incidence area.</p>

Association of thymidylate synthase polymorphism with esophageal squamous-cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the influence of 5'UTR tandem repeat and 3'UTR 6 bp deletion polymorphism of thymidylate synthase (TS) gene on the development and lymphatic metastases of esophageal squamous-cell carcinoma (ESCC).</p><p><b>METHODS</b>Peripheral leucocyte DNA was extracted from 232 ESCC patients and 348 age- and sex-matched healthy controls. TS 5'UTR and 3'UTR genotyping in all study subjects was performed by PCR fragment analysis and PCR-RFLP analysis, respectively.</p><p><b>RESULTS</b>The distribution of TS 5'UTR and 3'UTR variants in ESCC patients was not significantly different from that in healthy controls. However, individuals with 6 bp+/6 bp+ and 3R/3R genotypes significantly reduced the risk to ESCC development compared to those with other genotype combinations (adjusted OR = 0.32, 95% CI = 0.08-0.92). In addition, the frequency of 2R/3R genotype in ESCC patients with lymphatic metastases (40%) was significantly higher than that in lymph node negative cases (14.7%) (chi(2) = 10.11, P = 0.001). Compared to 3R/3R genotype, the 2R/3R genotype significantly increased the risk of lymphatic metastases in ESCC (adjusted OR = 3.68, 95% CI = 1.54-8.93).</p><p><b>CONCLUSION</b>The genotyping of TS 5'UTR and 3'UTR polymorphisms might be used as a stratification maker for predicting susceptibility to ESCC. The TS 5'UTR 2R/3R genotype might be a candidate molecular marker to predict the potential of lymphatic metastases in ESCC.</p>

The NAD(P)H: quinone oxidoreductase 1 C609T polymorphism and susceptibility to esophageal cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a northern Chinese population.</p><p><b>METHODS</b>The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis in 193 patients with ESCC and 141 unrelated healthy controls.</p><p><b>RESULTS</b>The frequency of the T allele (null) among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.86, P=0.028). The NQO1 C/C and C/T genotype distribution among ESCC patients was not significantly different from that among healthy controls (Chi-square= 2.27 and 0.127; P=0.132 and 0.721, respectively). However, the T/T genotype frequency among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.39, P=0.036). The NQO1 T/T genotype significantly increased the risk for developing ESCC, compared to the combination of C/C and C/T genotypes, with the adjusted odds ratio (OR) of 1.81 (95%CI: 1.04-3.15). This increased susceptibility exhibited pronouncedly in patients with family history of upper gastrointestinal cancers (adjusted OR=2.22, 95%CI 1.18-4.17).</p><p><b>CONCLUSION</b>Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate high-risk individuals for ESCC.</p>

p53 gene polymorphism with susceptibility to esophageal cancer and lung cancer in Chinese population / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association of p53 codon 72 polymorphism with susceptibility to esophageal cancer and lung cancer in the northern Chinese population.</p><p><b>METHODS</b>p53 codon 72 genotyping was performed by amplifying DNA fragments with sequence specific primers among 173 patients with esophageal squamous cell carcinoma, 98 with non-small cell lung carcinoma as well as 136 healthy controls.</p><p><b>RESULTS</b>No significant difference of p53 allelotype and genotype distribution was observed between esophageal cancer and lung cancer patients. The Pro allele frequency was significantly higher among esophageal cancer and lung cancer patients than among healthy controls (P value was 0.024 and 0.027 respectively). There were no significant differences in Pro/Arg and Arg/Arg genotype frequency among cancer patients and healthy controls (P > 0.05). However, the Pro/Pro genotype frequency was significantly higher among esophageal cancer and lung cancer patients than among healthy controls (P value was 0.041 and 0.026 respectively). The risk of Pro homozygotes for both esophageal cancer and lung cancer was about 2 times against Arg homozygotes with adjusted odds ratio of 2.12 (95% CI = 1.13 - 4.01) and 2.30 (95% CI = 1.13 - 4.93), respectively. There was no interaction between p53 Pro/Pro genotype and smoking status to the risk for esophageal cancer and lung cancer.</p><p><b>CONCLUSION</b>In the northern Chinese population, p53 Pro/Pro genotype is an independent risk factor for both esophageal cancer and lung cancer. The possible common genetic basis of the development of these two cancers is suggested by this study.</p>