[SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis].

Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals (P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA (P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased (P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged (P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

[Analysis on incidence trend of liver cancer in China, 2005-2016].

Objective: To understand the incidence trend of liver cancer in China from 2005 to 2016, and explore the correlation between the incidence trend of liver cancer and the incidence trend of hepatitis B. Methods: The incidence data of liver cancer in China from 2005 to 2016 were collected from the Annual Report of Cancer Registry in China. The incidence data of hepatitis B were collected from China Public Health Science Data Center. World standardized incidence rate (WSR) was calculated according to the World Segi's population. Joinpoint regression model was used to analyze the trend of WSR of liver cancer [measured by average annual percentage change (AAPC)]. The age-period-cohort model was fitted to analyze the age, period and cohort effects in people aged 20- years and above. Pearson correlation coefficient was used to explore the correlation between the incidence of liver cancer and the incidence of hepatitis B. Results: The crude incidence of liver cancer in China showed a trend of first increase before 2009 and then relatively stable. The world standardized morbidity rate of liver cancer in China decreased from 19.11 per 100 000 in 2005 to 17.74 per 100 000 in 2016 (AAPC=-0.5%, 95%CI: -1.3%-0.3%, P=0.240). The incidence of liver cancer in male decreased significantly (AAPC=-1.0%, 95%CI: -1.5%--0.5%, P=0.001). The incidence of liver cancer in women increased from 2005 to 2010 [annual percentage change (APC)=1.7%, 95%CI: -0.1%-3.4%, P=0.059] but showed a significant decrease trend from 2010 to 2016 (APC=-1.6%, 95%CI: -2.3%--1.0%, P=0.001). From 2005 to 2016, the incidence of liver cancer showed a decreasing trend in urban areas (AAPC=-0.3%, 95%CI: -0.8%-0.3%, P=0.316) and rural areas (AAPC=-3.9%, 95%CI: -4.4%--3.3%, P<0.001). Risk for liver cancer increased with age, while the period effect showed a trend of first increase then decrease and cohort effect showed a decrease trend. The morbidity rates of both hepatitis B and liver cancer showed decrease trends from 2009 to 2016, and there was a significant correlation (r=0.71, 95%CI: 0.01-0.94, P=0.048). Conclusions: From 2005 to 2016, the morbidity rate of liver cancer in China showed a decrease trend, and there were significant gender and urban-rural area specific differences. Age effect had a great impact on the risk for liver cancer. With the progress of population aging in China, liver cancer is still a public health problem, to which close attention needs to be paid.

[Clinical characteristics and prognosis of 49 newly diagnosed primary central nervous system diffuse large B-cell lymphoma].

Objective: The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively. Methods: A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis. Results: The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively (P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively (P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion: The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

[Facilitating the continuous decline on the incidence rates of hepatitis B and liver cancer through cutting off the mother-to-child viral transmission, based on the "prevention first" strategy, in China].

There have been 6-10 million reported patients with chronic hepatitis B virus (HBV) infection worldwide, and the United Nations (UN) called for a "90% reduction by 2030" strategy. Since the wide practice of HBV vaccination, the numbers of HBV cases have been reduced by 85% and the incidence of hepatocellular carcinoma has also decreased by 50%. As formulated by the UN in 2015, the sustainable development agenda for the eradication of hepatitis B included the success rate of preventing mother-to-child viral transmission by 95%, together with the reduction of new hepatitis B infections by 90% in 2030. In order to achieve the agenda, we proposed a strategy to achieve the "three 96%" goals derived from the Shanghai experience. In brief, hepatitis B vaccine should cover for 96% newborns within 24 h, and the vaccination boosting rate should reach 96% for both one and six months after birth. If cutting off the mother-to-child viral transmission strategy can be successfully achieved, the future of hepatitis B prevention will be promising, and the task of eliminating hepatitis B and controlling hepatocellular carcinoma can be completed ahead of 2030, time proposed by the UN.

[Schistosomiasis must be eradicated: a review of fighting schitosomiasis in Qingpu, Shanghai].

Qingpu, in western suburban of Shanghai, was one of serious schistosomiasis endemic counties in China. In 1958, in response to Chairman Mao' s call " Schistosomiasis must be eradicated", Shanghai First Medical College organized a research group to carry out schitosomiasis control in Qingpu. The prevalence of schistosomiasis was about 39% in 390 000 people and 8.4% in cattle. Oncomelania was distributed in an area of 70 million meter(2). The fighting project could be divided into two steps, the first one was from 1958 to 1974, during this period, the epidemic survey and patient treatment were conducted, and oncomelania control was carried out by using different kind of molluscides. In 1975, up to 92% of patients were cured, and 98% of oncomelania were killed. The second step was from 1975 to 1985, the main tasks were the consolidation of control achievement and surveillance. During this period oral medicines were used instead of venous injections. After the improvement of oncomelania detection method, the oncomelania clustering were found under rock duck and brick shore. In 1985, it was confirmed that schistosomiasis had been eradicated in Qingpu and other suburb areas of Shanghai.

Reliability and relative validity of three physical activity questionnaires in Taizhou population of China: the Taizhou Longitudinal Study.

OBJECTIVE: To examine the test-retest reliabilities and relative validities of the Chinese version of short International Physical Activity Questionnaire (IPAQ-S-C), the Global Physical Activity Questionnaire (GPAQ-C), and the Total Energy Expenditure Questionnaire (TEEQ-C) in a population-based prospective study, the Taizhou Longitudinal Study (TZLS). STUDY DESIGN: A longitudinal comparative study. METHODS: A total of 205 participants (male: 38.54%) aged 30-70 years completed three questionnaires twice (day one and day nine) and physical activity log (PA-log) over seven consecutive days. The test-retest reliabilities were evaluated using intra-class correlation coefficients (ICCs) and the relative validities were estimated by comparing the data from physical activity questionnaires (PAQs) and PA-log. RESULTS: Good reliabilities were observed between the repeated PAQs. The ICCs ranged from 0.51 to 0.80 for IPAQ-C, 0.67 to 0.85 for GPAQ-C, and 0.74 to 0.94 for TEEQ-C, respectively. Energy expenditure of most PA domains estimated by the three PAQs correlated moderately with the results recorded by PA-log except the walking domain of IPAQ-S-C. The partial correlation coefficients between the PAQs and PA-log ranged from 0.44 to 0.58 for IPAQ-S-C, 0.26 to 0.52 for GPAQ-C, and 0.41 to 0.72 for TEEQ-C, respectively. Bland-Altman plots showed acceptable agreement between the three PAQs and PA-log. CONCLUSION: The three PAQs, especially TEEQ-C, were relatively reliable and valid for assessment of physical activity and could be used in TZLS.

Analysis of intervertebral disc-related genes.

Intervertebral disk disease is a common clinical disorder manifested by pain, ataxia, paresis, motor paralysis, and sensorimotor paralysis. The clinical features, diagnosis, and treatment of cervical and thoracolumbar disk disease have been unclear until now. In this study, some differentially expressed genes were identified, and a network was constructed based on these genes. Through the statistical analysis of nodes and the contrast of 2 more connectivity nodes, it was found that the nodes in the network are in an important position and play key roles. Several of these genes, including MAP2K6, MAP2K3, and MAPK14, belong to the MAP kinase family, and several genes, including RHOBTB2, RHOQ, and RHOH, belong to the RHO family. Therefore, we hypothesize that the development of intervertebral disk disease is related to MAP and RHO family proteins.

The treatment of mild cervical spondylotic myelopathy with increased signal intensity on T2-weighted magnetic resonance imaging.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: To compare clinical outcomes of surgery or non-operated treatment for mild cervical spondylotic myelopathy (CSM) patients with intramedullary increased signal intensity (ISI) on T2-weighted imaging (T2WI) of magnetic resonance imaging (MRI), related factors that may affect prognosis were explored. METHODS: Data from 91 patients treated from July 2008 to June 2011 were retrospectively analyzed. The Japanese Orthopedic Association (JOA) recovery ratio was used to compare outcomes of surgery and non-operated treatment. Correlation and multiple linear regression analyses were performed between JOA recovery ratio and age, disease course, segmental lordosis, total range of motion (ROM), segmental ROM, local slip, extent of spinal cord compression or ISI type. RESULTS: Patients were divided into two groups by therapy methods: Group A (n=53, 33 males, age 36-68 years) underwent anterior cervical decompression and fusion surgery, average follow-up 30.68±8.19 months; Group B (n=38, 14 males, age 28-76 years) received non-operated treatment, average follow-up 34.08±9.05 months. There were no significant differences in clinical outcomes between the two groups. There were significant correlations between JOA recovery ratio and clinical course (P<0.01) or segmental lordosis (P<0.01). Patients with shorter disease course and larger segmental lordosis have better clinical outcomes as shown by multiple linear regression analysis. CONCLUSION: For mild CSM patients with ISI on T2WI-MRI, there are no significant differences in clinical outcome between surgery and non-operated treatment during the short-term follow-up. Patients with shorter disease course and larger segmental lordosis have better clinical outcomes than those with longer course and segmental kyphosis.

Polymorphisms of 5,10-methylenetetralydrofolate reductase (MTHFR), fruit and vegetable intake, and the risk of stomach cancer.

Stomach cancer is a serious public health problem in China. 5,10-Methylenetetralydrofolate reductase (MTHFR) may be involved in both DNA methylation and DNA synthesis. Folate deficiency is associated with cancer risk that may be modulated by a genetic variation in the MTHFR gene in folate metabolism. The main goal of this study was to evaluate the association between polymorphisms of the MTHFR gene and the risk of stomach cancer. This study also explored the modification effects of fruit and vegetable intake (one of the main constituents is folate) on the risk of this disease. A population-based case-control study was conducted in Taixing, China, consisting of 206 newly diagnosed cases with primary stomach cancer and 415 healthy population controls. Polymorphisms of MTHFR C677T and A1298C were assayed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) techniques. The data were analysed using the logistic regression model. No obvious association between the MTHFR A1298C polymorphism and the risk of stomach cancer was observed in this study. The frequencies of 677 C/C, C/T, and T/T were 34.5, 50.9, and 14.6%, respectively, in controls. The frequency of the MTHFR 677 wild homozygotic genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratio (OR) for the MTHFR 677 any T genotype was 2.05 (95% confidence interval (CI), 1.26-3.34) when compared with the C/C genotype. In the low fruit and vegetable intake group an increasing trend was observed with the T allele exposure, p = 0.0056. The adjusted ORs were 1.68 (95% CI = 0.86-3.29) for the C/T genotype and 3.58 (95% CI = 1.46-8.75) for the T/T genotype, respectively. The MTHFR 677 any T genotype was associated with an increased risk of primary stomach cancer among the Chinese population. Folate deficiency might modify the MTHFR gene polymorphism and influence the risk of stomach cancer.

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo.

Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400-2420) and the 3'-coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense- and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense- and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense- and siRNA-treated groups than the control groups. Our results demonstrated that antisense- or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.

Maternal and gestational correlates of pregnancy prolactin and growth hormone in USA and China.

The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent, prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other.

GSTP1 polymorphisms and gastric cancer in a high-risk Chinese population.

OBJECTIVES: In a population-based case-control study in Yangzhong, China, we investigated the relationship between genetic polymorphisms of GSTP1 and susceptibility to gastric cancer and its premalignant lesion, chronic gastritis. The possible gene-gene interactions between GSTP1 polymorphisms and GSTM1, GSTT1 genes were explored. METHODS: Epidemiologic data were collected by standard questionnaire from 133 gastric cancer cases, 166 chronic gastritis cases, and 433 cancer-free population controls. Blood samples for Helicobacter pylori and molecular marker assays were collected from 84 gastric cancer cases, 146 chronic gastritis, and 429 population controls. GSTP1 polymorphisms were determined by the PCR-RFLP method and H. pylori infection was measured by the ELISA method. Associations between certain GSTP1 genotypes and both gastric cancer and chronic gastritis were assessed by odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression. RESULTS: The distributions of three GSTP1 genotypes, Ile/Ile, Ile/Val, and Val/Val, were similar in gastric cancer cases, chronic gastritis, and controls. After adjusting for age, gender, education, body mass index, pack-year of smoking, alcohol drinking, H. pylori infection, salt and fruit intakes, the adjusted ORs of Val/Val were 1.3 (95% CI: 0.1-11.2) for gastric cancer and 0.9 (95% CI: 0.2-4.8) for chronic gastritis. Combining the Val alleles (Val/Val and Ile/Val) into one group, no association was observed between GSTP1 and both gastric cancer and chronic gastritis. In addition, the allelism at the GSTP1 locus did not increase gastric cancer and chronic gastritis risks associated with the GSTM1 or GSTT1 genotypes. CONCLUSION: Our data suggest that the GSTP1 genotype seems not to be associated with the risk of gastric cancer and chronic gastritis in a high-risk Chinese population.

Protective effect of green tea on the risks of chronic gastritis and stomach cancer.

Despite the declining trend, stomach cancer remains the second most common cancer worldwide. We examined the role of green tea consumption on chronic gastritis and stomach cancer risks. A population-based case-control study was conducted in Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and 433 healthy controls. Epidemiologic data were collected by standard questionnaire and odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models in SAS. Inverse association was observed between green tea drinking and chronic gastritis and stomach cancer risks. After adjusting for age, gender, education, body mass index, pack-years of smoking and alcohol drinking, ORs of green tea drinking were 0.52 (95% CI: 0.29-0.94) and 0.49 (95% CI: 0.31-0.77) for stomach cancer and chronic gastritis, respectively. In addition, dose-response relationships were observed with years of green tea drinking in both diseases. The results provide further support on the protective effect of green tea against stomach cancer. This is the first time that green tea drinking was found to be protective against chronic gastritis, which may be of importance when designing intervention strategies for stomach cancer and its pre-malignant lesions in the high-risk population.

[Expression of P21 WAF1/CIP1 in human astrocytomas in correlating with P53, MDM2, and cellular proliferation index].

OBJECTIVE: To study the correlation between the expression of p21, p53, MDM2 gene products and the initiation and progression of human astrocytomas. METHODS: The expression of P21, P53, MDM2, and proliferative cell nuclear antigen (PCNA) labeling index using immunohistochemistry in 41 paraffin embedded human astrocytoma samples. As well as the expression of p21 mRNA using mRNA in situ hybridization in 24 fresh human astrocytoma samples stored at -70 degrees C were investigated. In immunohistochemistry, we divided whole tumor cells by positive tumor cell nuclei to obtain labeling index (LI), in this way we could understand the protein product expression of gene in astrocytoma in different patients. In mRNA in situ hybridization, the expression of p21 mRNA was scored according to the rough percentage of positive cells. RESULTS: In p21 mRNA in situ hybridization, the positive staining was present in 87.5%. In immunohistochemistry, positive P21, P53, MDM2, and PCNA staining were presented in 75.6%, 68.3%, 65.9%, 100% respectively. Higher levels of P21 protein expression were seen in higher histological grade (P = 0.001). The association between P21 expression positively correlated with proliferation index. But not with P53 expression and MDM2 expression. The association between P53 expression and proliferation indices were statistically significant, but the expression of P53 was not related to tumor grade. There was no association between MDM2 expression and grade, or cellular proliferation index. Linear stepwise regression analysis showed the parameters affecting tumor grade were PCNA LI (P = 0.000) and P21 LI (P = 0.001). CONCLUSIONS: (1) Both p21 mRNA and P21 protein were overexpressed in human astrocytomas, the overexpression was related to cellular proliferation index, but was not related to P53 expression, suggesting there could be P53-independent pathway to induce the P21 expression, in addition, the overexpression of P21 alone appeared insufficient to suppress tumor growth, provided the participation of PCNA. (2) The expression of P53 protein was associated with proliferation indices, but was not with the tumor malignancy, this indicated that the inactivation of P53 might be the early event in the growth of human astrocytomas. (3) P21 labeling index and cellular proliferation index influenced the tumor histological grade, our data indicated that p21 gene might play a role in the progression of human astrocytomas.

Glutathione S-transferases M1, T1 genotypes and the risk of gastric cancer: a case-control study.

AIM: Glutathione S-transferases (GSTs) are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione S-transferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTT1 and GSTT1 and gastric cancer. METHODS: A population based case-control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTT1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis. RESULTS: An increase in risk for gastric cancer was found among carriers of GSTT1 null genotype. The adjusted odds ratio (OR) was 2.63 95% Confidence Interval (95% CI) 1.17-5.88, after controlling for age, gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTT1 null and GSTT1 non-null genotype was significantly higher than in those with both GSTT1 and GSTT1 non-null genotype (OR = 2.77, 95% CI 1.15-6.77). Compared with those subjects who never smoked and had normal GSTT1 genotype, ORs were 1.60 (95% CI:0.62-4.19) for never smokers with GSTT1 null type, 2.33 (95% CI 0.88-6.28) for smokers with normal GSTT1, and 8.06 (95% CI 2.83-23.67) for smokers with GSTT1 null type. CONCLUSIONS: GSTT1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco-related carcinogenesis of gastric cancer.

Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle, Fujian Province.

AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.

GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population.

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. The homozygous deletions or null genotypes of GSTT1 (theta class) and GSTM1 (mu class) genes may be associated with an increased risk of cancer. Few studies have evaluated the relationship between GSTT1, GSTM1 and the risk of gastric cancer, as well as the potential interactions between these genetic markers and other risk factors of gastric cancer in the Chinese population. We conducted a case-control study with 143 cases with gastric cancer, 166 chronic gastritis (CG) cases and 433 cancer-free population controls from Yangzhong County, China. The epidemiological data were collected by a standard questionnaire for all of the subjects, and blood samples were obtained from 91 gastric cancer cases, 146 CG cases, and 429 controls. GSTT1 and GSTM1 genotypes were assayed by the PCR method, and Helicobacter pylori infection was measured by the ELISA method. Using logistic regression model in SAS, we assessed the independent effects of GSTT1 and GSTM1 null genotypes on the risk of gastric cancer and their potential interactions with other factors. The prevalence of GSTM1 null genotype was 48% in gastric cancer cases, 60% in CG patients, and 51% in controls. The prevalence of GSTT1 null genotype was 54% in gastric cancer cases, 48% in CG patients, and 46% in controls. After controlling for age, gender, education, pack-years of smoking, alcohol drinking, body mass index, H. pylori infection, and fruit and salt intake, the adjusted odds ratio (OR) for GSTT1 and gastric cancer was 2.50 (95% confidence interval (CI), 1.01-6.22). When gastric cancer cases were compared with CG patients, the adjusted OR for GSTT1 was 2.33 (95% CI, 0.75-7.25). However, GSTT1 null genotype was not associated with the risk of CG when using population controls. No obvious association was found between GSTM1 and the risk of both gastric cancer and CG. Our results suggest that GSTT1 null genotype may be associated with an increased risk of gastric cancer in a Chinese population.

Maternal pregnancy hormone levels in an area with a high incidence (Boston, USA) and in an area with a low incidence (Shanghai, China) of breast cancer.

Characteristics probably associated with the fetal hormonal milieu have recently been shown to increase (birth size indicators, prematurity, neonatal jaundice) or decrease (pregnancy toxaemia) breast cancer risk in the female offspring. However, it is unknown whether differences in pregnancy hormone levels may contribute to the marked geographical variation in breast cancer incidence. We have compared, in a highly standardized manner, pregnancy hormone levels in a population with high incidence and one with low incidence of breast cancer. Three hundred and four pregnant Caucasian women in Boston and 334 pregnant Chinese women in Shanghai were enrolled from March 1994 to October 1995. Levels of oestradiol, oestriol, prolactin, progesterone, human growth hormone, albumin and sex hormone-binding globulin were measured in maternal blood at weeks 16 and 27 of gestation and compared between the two study sites using non-parametric Wilcoxon's rank-sum test. Demographical, anthropometrical and pregnancy characteristics were ascertained through interview, and relevant variables concerning delivery and the newborn were abstracted from medical records and paediatric charts. During the first visit, median serum levels of all studied hormones were statistically significant, and in most instances substantially, higher among Chinese women, who have a low incidence of breast cancer, compared with American women, who have a high incidence of breast cancer. An analogous pattern was evident during the second visit, although the relative differences tended to be smaller. Further research is needed to identify lifestyle or other exogenous determinants of pregnancy hormone levels, as well as possible mechanisms by which they may influence carcinogenic processes in the breast and possibly other organs.

Enhancement of glutathione S-transferase placental-form positive liver cell foci development by microcystin-LR in aflatoxin B1-initiated rats.

The objective of this study was to elucidate whether microcystin-LR (MC-LR), a hepatotoxic blue-green algal toxin in drinking water, is carcinogenic or possesses the ability to modulate aflatoxin B1 (AFB1)-induced hepatocarcinogenicity. In a medium-term liver bioassay, male Fischer 344 rats were given a single i.p. injection of diethylnitrosamine (DEN, 200 mg/kg) followed by an i.p. injection of MC-LR for 6 weeks after 2 weeks of DEN treatment. To study the synergism between AFB1 and MC-LR, DEN-treated rats were given an i.p. injection of AFB1 (0.5 mg/kg) dissolved in dimethyl sulfoxide (DMSO) followed by MC-LR at 2 weeks after the treatment. In a separate experiment, the rats were first given AFB1 (0.5 mg/kg) and 2 weeks later an i.p. injection of 1 or 10 microg/kg of MC-LR twice a week for 6 weeks. Most rats were subjected to a two-thirds partial hepatectomy (PH) at week 3 and were killed under anesthesia at week 8. Liver sections were analyzed for glutathione S-transferase placental form (GST-P) expression, and subjected to histopathological examination for phenotypic alteration of hepatocellular foci. In rats that did not receive DEN, MC-LR did not cause a significant increase in the numbers of GST-P-positive foci, whereas AFB1 induced a slight increase in GST-P-positive foci development. In rats given DEN, MC-LR enhanced the expression of GST-P-positive foci, as did AFB1 but no synergism was observed. Histopathological analysis revealed that the area of eosinophilic foci, a biomarker for preneoplastic liver lesion, markedly increased because of MC-LR. In rats given AFB1 as an initiator, treatment with MC-LR resulted in a synergistic increase in the development of GST-P-positive foci. These results suggest that the hepatocarcinogenicities of MC-LR and AFB1 can be predicted in experimental animals with a medium-term bioassay. Furthermore, tumor promoting activity of MC-LR was demonstrated in rats treated with AFB1.