Upper gastrointestinal cancer burden in Hebei Province, China: A population-based study.

AIM: To investigate the incidence and mortality rates of upper gastrointestinal cancer (UGIC) in Hebei Province, China, and to identify high-risk populations to improve UGIC prevention and control. METHODS: Data for UGIC patients were collected from 21 population-based cancer registries covering 15.25% of the population in Hebei Province. Mortality data were extracted from three national retrospective death surveys (1973-1975, 1990-1992 and 2004-2005). The data were stratified by 5-year age groups, gender and area (high-risk/non-high-risk areas) for analysis. The age-period-cohort and grey system model were used. RESULTS: The crude incidence rate of UGIC was 55.47/100000, and the adjusted rate (Segi's population) was 44.90/100000. Males in rural areas had the highest incidence rate (world age-standardized rate = 87.89/100000). The crude mortality rate of UGIC displayed a decreasing trend in Hebei Province from the 1970s to 2013, and the adjusted rate decreased by 43.81% from the 1970s (58.07/100000) to 2013 (32.63/100000). The mortality rate declined more significantly in the high-risk areas (57.26%) than in the non-high-risk areas (55.02%) from the 1970s to 2013. The median age at diagnosis of UGIC was 65.06 years in 2013. There was a notable delay in the median age at death from the 1970s (66.15 years) to 2013 (70.39 years), especially in the high-risk areas. In Cixian, the total trend of the cohort effect declined, and people aged 65-69 years were a population at relatively high risk for UGIC. We predicted that the crude mortality rates of UGIC in Cixian and Shexian would decrease to 98.80 and 133.99 per 100000 in 2018, respectively. CONCLUSION: UGIC was the major cause of cancer death in Hebei Province, and males in rural areas were a high-risk population. We should strengthen early detection and treatment of UGIC in this population.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Analysis of risk factors for upper gastrointestinal cancer in China: a multicentric population-based case-control study].

OBJECTIVE: To explore the major risk factors for upper gastrointestinal cancer in high occurrence areas of esophageal and gastric cancer in China. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

[A population-based matched case-control study on the risk factors of gastric cardia cancer].

OBJECTIVE: To find the major risk factors associated with gastric cardia cancer. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Natural history of esophageal and gastric cardia precursor by repetitive endoscope screening with 425 adults in a high-risk area in China.

OBJECTIVE: To observe the natural history and to determine appropriate screening interval for esophageal and gastric cardia precursors. METHODS: Repetitive endoscopic screenings were performed among 425 forty to sixty-nine-year-old subjects in a high-risk region in Northern China. RESULTS: We observed 8 subjects develop severe dysplasia (SD), another 8 develop carcinomas in situ (Cis), and 4 develop invasive cancer. The time and baseline diagnosis (BD) for the 8 SD subjects were: 13 months after normal epithelium in one case, 7 months after base cell hyperplasia (BCH) in another case, 3, 4, 4, and 10.5 months after mild dysplasia (mD) in four cases, and 12.5 and 43.4 months after moderate dysplasia (MD) in two cases. The time and BD for the 8 Cis cases were: 18 and 51.7 months after BCH in two cases, 48 months after mD in one case, 4 and 13 months after MD in two cases, and 3.5, 9, and 17.5 months after SD in the other three cases. The time and BD for the four invasive cancer cases were, 13 months after mD in one case, 50 months after MD in another case, and 14 and 19 months after SD in two cases. In addition to natural history observation, we also found sex, age (over 50 vs under 50), family history of upper gastrointestinal cancer, and the presence of multiple esophageal lugol-void lesions to be significant predicators for dysplastic progression; the corresponding OR (95% CI) and P-value were 1.98 (1.14-3.46) and 0.02; 2.32 (1.29-4.19) and 0.004; 1.81 (1.06-3.11) and 0.03; and 4.67 (2.70-8.06) and 0.000 respectively. CONCLUSIONS: A 5-year screening interval for BCH and mD, and a 3-year interval for MD, as suggested in China in 2005, may be too long for rapid developing precursors or individuals at high-risk for dysplastic progression. Therefore, shorter intervals should be considered.

[Establishment of a diagnostic model of serum protein fingerprint pattern for esophageal cancer screening in high incidence area and its clinical value].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

[Correlation of 53BP1 and p53 polymorphisms to susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

BACKGROUND & OBJECTIVE: 53BP1 is one of p53-binding proteins, which can enhance the transcriptional activation of p53 and plays a key role in tumor suppression. A single nucleotide polymorphism (SNP) T885G has been found in the promoter of 53BP1. This study was to investigate the correlation of 53BP1 and p53 SNPs to susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a high incidence area of Hebei Province in China. METHODS: Genotypes of 53BP1 T885G and p53 Arg72Pro in 349 ESCC patients, 275 GCA patients, and 635 healthy subjects were detected by primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR). RESULTS: The overall distribution of 53BP1 T885G was not significantly different between ESCC patients, GCA patients and healthy subjects (P>0.05). When stratified by smoking status and family history of upper gastrointestinal cancer (UGIC), the distribution of 53BP1 T885G was not significantly different between ESCC patients, GCA patients and healthy subjects. Compared with p53 Arg72Pro Arg/Arg genotype, Pro/Pro genotype decreased the susceptibility to GCA [the age, sex, smoking status, and family history adjusted odds ratio (OR)=0.79, 95% confidence interval (CI)=0.64-0.98]. Stratification analysis showed that Pro/Pro genotype decreased the susceptibility to GCA among non-smokers (adjusted OR=0.72, 95% CI=0.54-0.97), but p53 Arg72Pro had no influence on the susceptibility to ESCC. Stratified by p53 Arg72Pro genotype, 53BP1 T885G G/G genotype reduced the susceptibility to GCA among the individuals with Pro allele (Arg/Pro and Pro/Pro genotypes) (adjusted OR=0.74, 95% CI=0.57-0.95). CONCLUSION: 53BP1 T885G may not be correlated to the susceptibility to ESCC and GCA in the high incidence area of Hebei Province in China; p53 Arg72Pro Pro/Pro genotype could decrease the susceptibility to GCA; 53BP1 T885G G/G genotype could reduce the susceptibility to GCA among the individuals with p53 Pro allele.

[Correlations between serine hydroxymethyltransferase1 C1420T polymorphisms and susceptibilities to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

BACKGROUND & OBJECTIVE: Serine hydroxymethyltransferase (SHMT), a key enzyme in the folate metabolism, affects gene methylation and DNA synthesis through providing one-carbon units for purine, thymidylate, and methionine. It is closely related to the development and progression of tumors. This study was to investigate the correlations between SHMT1 C1420T single nucleotide polymorphisms (SNP) and susceptibilities to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). METHODS: SHMT1 C1420T SNP was genotyped by polymerase chain reaction-confronting two-pair primers (PCR-CTPP) analysis in 584 ESCC patients, 467 GCA patients, and 540 healthy controls. The correlations between SHMT1 C1420T SNP polymorphisms and susceptibilities to ESCC and GCA were analyzed with Logistic regression model. RESULTS: Family history of upper gastrointestinal cancer (UGIC) significantly enhanced the risk of developing ESCC and GCA [the age, gender, smoking status, and family history of UGIC adjusted odds ratio (OR)=2.89, 95% confident interval (CI)=2.23-3.73; OR =1.68, 95% CI=1.28-2.23]. The frequency of 1420C/T genotype was significantly lower in ESCC and GCA patients than in healthy controls (12.0% vs. 16.5%, P<0.05; 10.9% vs. 16.5%, P<0.01). Compared with C/C genotype, C/T genotype significantly reduced susceptibilities to ESCC and GCA, with adjusted OR of 0.70 (95% CI=0.50-0.98) for ESCC and 0.55 (95% CI=0.38-0.81) for GCA. Stratification analysis showed that C/T genotype significantly reduced susceptibilities to ESCC and GCA among non-smokers, with adjusted OR of 0.54 (95% CI=0.33-0.90) for ESCC and 0.56 (95% CI=0.33-0.95) for GCA. In addition, C/T genotype significantly reduced susceptibility to GCA among individuals with or without UGIC history, with adjusted OR of 0.46 (95%CI=0.24-0.90) and 0.62 (95% CI=0.38-0.99) respectively, and reduced susceptibility to ESCC only among individuals with UGIC history, with adjusted OR of 0.51 (95% CI=0.29-0.89). CONCLUSION: SHMT1 1420C/T genotype could significantly reduce susceptibilities to ESCC and GCA among individuals from high risk areas in Hebei Province of China.

[Association of thymidylate synthase polymorphism with esophageal squamous-cell carcinoma].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Single nucleotide polymorphism in DNA methyltransferase 3B promoter and its association with gastric cardiac adenocarcinoma in North China.

AIM: To investigate the association between single nucleotide polymorphism (SNP) in promoter of the DNA methyltransferase 3B (DNMT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA). METHODS: The hospital based case-control study included 212 GCA patients and 294 control subjects without overt cancer. The DNMT3B SNP was genotyped by PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The C/C genotype was not detected in both GCA patients and controls. In control subjects, the frequency of T/T and C/T genotypes was 94.9% and 5.1% respectively, and that of T and C alleles was 97.4% and 2.6%, respectively. The genotype and allelotype distribution in the GCA patients was not significantly different from that in controls (P=0.34 and 0.33, respectively). When stratified by smoking status and family history of upper gastrointestinal cancer, significant difference in the genotype distribution was not observed between GCA patients and controls. The distribution of DNMT3B genotypes in GCA patients with or without lymphatic metastasis did not show significant difference (P=0.42). CONCLUSION: The distribution of DNMT3B SNP in North China is distinct from that in Caucasians. Although this SNP has been associated with susceptibility to lung, head, neck and breast cancer, it may not be used as a stratification marker to predict susceptibility and lymphatic metastasis of GCA, at least in the population of North China.

No association of the matrix metalloproteinase 1 promoter polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in northern China.

AIM: To investigate association of the 2G or 1G single nucleotide polymorphism (SNP) in matrix metalloproteinase 1 (MMP1) promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of North China. METHODS: MMP1 promoter SNP was genotyped by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 417 cancer patients (234 ESCC and 183 GCA) and 350 healthy controls. RESULTS: The genotype frequencies of the MMP1 promoter SNP in healthy controls were 55.4% (2G/2G), 30% (1G/2G) and 14.6% (1G/1G), respectively. The genotype and allelotype distribution in ESCC and GCA patients was not significantly different from that in healthy controls (all P values were above 0.05). Compared with the 1G/1G genotype, neither the 2G/2G nor in combination with the 1G/2G genotype significantly modified the risk of developing ESCC and GCA, the adjusted odds ratio was 1.28 (95%CI = 0.78-2.09), 1.23 (95%CI = 0.38-2.05) in ESCC and 1.39 (95%CI = 0.80-2.41), 1.34 (95%CI = 0.74-2.40) in GCA, respectively. When stratified by smoking status and family history of upper gastrointestinal cancer, the 2G/2G genotype alone or in combination with the 1G/2G genotype also did not show any significant influence on the risk of ESCC and GCA development. In addition, influence of the MMP1 SNP on lymphatic metastasis in ESCC and GCA was also not observed. CONCLUSION: The 2G or 1G SNP in the MMP1 promoter might not modify the risk of ESCC and GCA development and might not be used as a stratification marker to predict the potential of lymphatic metastasis in these two tumor types.

Interleukin-10 -1082 promoter polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high-incidence region of north China.

AIM: To investigate the possible association of G-A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China. METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203 ESCC and 152 GCA) and 443 healthy controls. RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42 and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively). Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10, 95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%, 39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6% and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P>0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95% CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46) in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes. CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.

[The NAD(P)H: quinone oxidoreductase 1 C609T polymorphism and susceptibility to esophageal cancer].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate high-risk individuals for ESCC.

Epoxide hydrolase Tyr113His polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma in population of North China.

AIM: To investigate the possible association of microsomal epoxide hydrolase (mEH) Tyr113His polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a population of North China. METHODS: The mEH Tyr113His genotypes were determined by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 257 patients with esophageal squamous cell carcinoma (ESCC) and 252 healthy subjects as a control group. RESULTS: The frequencies for Tyr and His alleles were 44.2%, 55.8% in ESCC patients, and 44.0% and 56.0% in healthy subjects, respectively. No statistic difference in allele distribution was observed between ESCC patients and controls (chi2=0.008, P=0.929). The overall genotype distribution difference was not observed between cancer cases and controls (chi2=2.116, P=0.347). Compared with Tyr/Tyr genotype, neither His/His genotype nor in combination with Tyr/His genotype significantly modified the risk of the development of ESCC, the adjusted odds ratio was 1.076 (95% CI=0.850-1.361) and 0.756 (95% CI=0.493-1.157), respectively. When stratified for sex, age, smoking status and family history of upper gastrointestinal cancer, His/His genotype alone or in combination with Tyr/His genotype also did not show any significant influence on the risk of developing ESCC. CONCLUSION: MEH Tyr113His polymorphism may not be used as a stratification marker in screening individuals at a high risk of ESCC.

[p53 gene polymorphism with susceptibility to esophageal cancer and lung cancer in Chinese population].

OBJECTIVE: To investigate the association of p53 codon 72 polymorphism with susceptibility to esophageal cancer and lung cancer in the northern Chinese population. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[The association of cyclin D1 (A870G) polymorphism with susceptibility to esophageal and cardiac cancer in north Chinese population].

OBJECTIVE: To investigate the association of Cyclin D1 (A870G) single nucleotide polymorphism (SNP) with the susceptibility to esophageal and cardiac cancer in northern Chinese population. METHODS: By polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP), the Cyclin D1 (A870G) genotyping was performed among 178 patients with esophageal or esophageal -gastric junction carcinoma (120 with esophageal squamous cell cancer and 58 with cardiac adenoma cancer) and 122 health controls. RESULTS: There were no significant differences in Cyclin D1 (A870G) allele frequencies between cancer patients and health controls (P = 0.075). There is no genotype distribution difference was found between non-smoker patients and controls (P > 0.05). The risk for esophageal and cardiac cancer is 2.5 times higher in A/A genotype carried smokers than that in A/G or G/G genotype carried non-smokers, with the adjusted Odd Ratio of 2.57 (95% confidence interval is 1.19 approximately 5.57). The G/G genotype reduces the susceptibility to esophageal cancer, with the adjusted Odd Ratio of 0.39 and 95% confidence interval of 0.18 - 0.82. The A/A frequency in cardiac patients (34.48%) is higher than that in health controls (23.77%) but the difference does not reach significant (P = 0.212). CONCLUSION: In northern Chinese population, the smoking individuals carrying Cyclin D1 (A870G) A/A genotype increase the susceptibility to esophageal and cardiac cancer. The G/G genotype probably plays a protecting role in the occurrence of esophageal cancer.

NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China.

AIM: To investigate the association of the NQO1 (C609T) polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in North China. METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 317 cancer patients (193 ESCC and 124 GCA) and 165 unrelated healthy controls. RESULTS: The NQO1 C609T C/C, C/T and T/T genotype frequency among healthy controls was 31.5 %, 52.1 % and 16.4 % respectively. The NQO1 T/T genotype frequency among ESCC patients (25.9 %) was significantly higher than that among healthy controls (chi(2)=4.79, P=0.028). The NQO1 T/T genotype significantly increased the risk for developing ESCC compared with the combination of C/C and C/T genotypes, with an age, sex and smoking status adjusted odds ratio (OR) of 1.78 (1.04-2.98). This increased susceptibility was pronounced in ESCC patients with family histories of upper gastrointestinal cancers (UGIC) (adjusted OR=2.20, 95 % CI=1.18-3.98). Similarly, the susceptibility of the NQO1 T/T genotype to GCA development was also observed among patients with family histories of UGIC, with an adjusted odds ratio of 2.55 (95 % CI=1.21-5.23), whereas no difference in NQO1 genotype distribution was shown among patients without family histories of UGIC. CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate the individuals at high risk for developing ESCC and GCA in North China.

Field population-based blocking treatment of esophageal epithelia dysplasia.

AIM: To confirm the value of blocking treatment by zenshengping (ZSP), a Chinese herb composite, and Riboflavin for esophageal epithelia dysplasia cases screened out in high risk area in northern china by exfoliative balloon cytology (EBC), so to reduce the incidence rate of esophageal cancer(EC). METHODS: Esophageal epithelium dysplasia cases including mind esophageal epithelium dysplasia (MEED), stage one severe esophageal epithelium dysplasia (SEED I), and stage two severe esophageal epithelium dysplasia (SEED II) were screened out from people aged 40 years and older in the high risk area of Chixian. These cases were randomly divided into a treatment and control group. Subjects in the treatment and control groups took ZSP, riboflavin, and placebo daily for three years. EC cases registered by cancer registry and identified by EBC re-screening in the treatment and control groups were used to calculate incidence and blocking rates to demonstrate the effects of blocking medication. RESULTS: It was found that 31.92% and 24.15% of people aged 40 years and older in Cixian could been diagnosed as MEED and SEED cases. The severity of dysplasia increased with age. ZSP had blocked EC occurrence by 47.79% after 3 year medication among the SEED cases. CONCLUSION: ZSP can block the development from SEED I and SEED II to EC by 47.79%. Efforts should be made to screen and treat dysplasia cases in people aged 40 years and older in high risk areas to reduce the mortality figures.