Bladder Cancer In Chinese Population Research Articles

Genetic risk scores based on risk-associated single nucleotide polymorphisms can reveal inherited risk of bladder cancer in Chinese population.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with bladder cancer (BCa) risk in Caucasian and East Asian population. The objective of this study was to validate these SNPs in Chinese population and evaluate whether these SNPs could differentiate the individual inherited risk for BCa.A case-control study including 581 BCa cases and 1561 healthy controls was performed. Germline DNA samples from all individuals were genotyped for eight SNPs. Genetic risk score (GRS) was calculated for each individual based on the odds ratios and risk allele frequencies of five risk-associated SNPs.Among eight SNPs evaluated in this study, rs798766 at 4p16.3 [OR = 1.39 (1.15-1.67), P < .001], rs9642880 [OR = 1.17 (1.06-1.30), P < .001] and rs4813953 at 20p12.2 [OR = 1.09 (1.02-1.17), P = .016] were found associated with BCa risk in Chinese population. A genetic risk score was established based on five SNPs (including the above three SNPs and two other SNPs which have the consistent direction with previous reported genome-wide association study). The mean GRS was significantly higher in BCa cases than controls (1.22 vs. 1.01, P < .001). When subjects were categorized into low- (<0.8), average- (0.8-1.2), and high-risk (>1.2) groups, the likelihoods of BCa were 25.2%, 33.7% and 55.0%, respectively (P-trend < 2.2 × 10). In subgroup analyses, no significant difference was observed in mean GRS among BCa patients with different stages or grades.In conclusion, two SNPs derived from East Asian and one SNP from Caucasian were associated with BCa risk in Chinese population. These results provided additional information of genetic risks for BCa in Chinese population. Genetic risk score based on these SNPs can reveal inherited risk of BCa, and may have potential for modifying personalized cancer screening strategy.

Correlation between gene polymorphisms of excision repair cross-complementing gene 1 and excision repair cross-complementing gene 2 and susceptibility to bladder cancer in Chinese population

Objective To investigate the relationship between single nucleotide polymorphisms of excision repair cross-complementing gene (ERCC) 1 (rs3212986) and ERCC2 (rs13181) gene and bladder cancer susceptibility in Chinese population. Methods A total of 194 patients with bladder cancer (case group) and 240 healthy subjects (control group) were enrolled. In the case group, there were 143 males and 51 females, 85 cases under 50 years old and 109 cases over 50 years old, body mass index (BMI) <25 154 cases and BMI ≥25 40 cases, 119 cases without smoking history and 75 cases with smoking history, 122 cases without drinking history and 72 cases with drinking history, 179 cases without family tumor history and 15 cases with family tumor history. In the control group, there were 145 males and 95 females; 121 cases under 50 years old and 119 cases over 50 years old, BMI <25 201 cases and BMI ≥25 39 cases, 176 cases without smoking history and 64 cases with smoking history, 169 cases without drinking history and 71 cases with drinking history, 224 cases without family tumor history and 16 cases with family tumor history. The genotypes of ERCC1 rs3212986 and ERCC2 rs13181 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between each genotype and the risk of bladder cancer was explored. Results There was a statistically significant difference in the distribution of ERCC1 rs3212986 genotype between the two groups (χ2=6.010, P 0.05). Conclusion The ERCC1 rs3212986 gene polymorphism affects the occurrence of bladder cancer in the codominant and recessive models. The ERCC2 rs13181 gene polymorphism is not associated with the risk of bladder cancer. Key words: Bladder cancer; Gene polymorphism; Excision repair cross-complementing gene

Association of rs8444 polymorphism in the LASS2 3'-UTR and bladder cancer risk in Chinese population.

The aim of the present study was to explore the correlations between single nucleotide polymorphisms in LASS2 gene 3'-untranslated regions and bladder cancer risk in Chinese population. We first performed PCR and sequence for LASS2-3'-UTR in 105 bladder cancer patients and 100 control subjects. Next, multivariate logistic regression analysis was used to determine the relationship between single nucleotide polymorphisms frequency and susceptibility of bladder cancer, and clinical features in 105 cases. In addition, survival curves and Cox Regression analysis were used to investigate the effect of single nucleotide polymorphisms on clinical outcome in 58 cases. Finally, quantitative reverse-transcription PCR and immunohistochemical were performed to explore the influence of single nucleotide polymorphisms on LASS2 expression. We found that a single nucleotide polymorphism (rs8444 C>T) located in the 3'-UTR of LASS2 was significantly associated with the risk of bladder cancer. We also showed the frequency of rs8444 T genotype was higher in bladder cancer group and correlated with the risk of clinical prognosis. Yet, there were no significant correlations between T/C allele frequencies and the distributions of rs8444 genotype and tumor-node-metastasis stage, histological grade and distant metastasis in bladder cancer. Furthermore, we demonstrated that rs8444 C>T could affect LASS2 expression by single nucleotide polymorphism-related mRNA stability. Our results showed that LASS2-3'-UTR rs8444 C>T polymorphism was significantly associated with the individual risk and the poor overall survival of bladder cancer, suggesting that rs8444 TT genotype maybe act as an independent risk factor of susceptibility and clinical prognosis for bladder cancer in Chinese population.

Association between lncRNA H19 (rs217727, rs2735971 and rs3024270) polymorphisms and the risk of bladder cancer in Chinese population.

The Long non-coding RNA (lncRNA) H19 is involved in carcinogenesis, progression, and metastasis. However, the association between genetic variants in H19 and bladder cancer susceptibility has not been reported. This case-control study assessed the association between H19 genetic variants and susceptibility to bladder cancer in a Chinese Han population. In this study, 200 patients with bladder cancer and 200 healthy controls were surveyed and compared for frequencies of the genotypes of the H19 gene. Logistic regression analysis and the chi-square test were employed as statistical methods. Odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were calculated to estimate the strength of association between H19 polymorphisms and risk of bladder cancer. We analyzed the frequency of three lncRNA H19 SNPs in 200 bladder cancer patients and 200 healthy controls. Carriers of variant rs217727 heterozygous genotype showed increased bladder cancer risk (P=0.008). Further stratified analyses revealed that the association between bladder cancer risk and variant genotypes of rs217727 was more profound in smokers. Furthermore, decreased risk of invasive bladder cancer was found in carrying rs3024270 CC patients. Our results provided the evidence that rs217727 in H19 was associated with elevated risk of bladder cancer, which may be a potential biomarker for predicting bladder cancer susceptibility. Furthermore, invasive bladder cancer in carrying rs3024270 CC genotype maybe have a good prognosis.

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3

Genome-wide association studies (GWAS) of bladder cancer have identified a number of susceptibility loci in European populations but have yet to uncover the genetic determinants underlying bladder cancer incidence among other ethnicities. Therefore, we performed the first GWAS in a Chinese cohort comprising 3,406 cases of bladder cancer and 4,645 controls. We identified a new susceptibility locus for bladder cancer at 5q12.3, located in the intron of CWC27 (rs2042329), that was significantly associated with disease risk (OR = 1.40; P = 4.61 × 10(-11)). However, rs2042329 was not associated with bladder cancer risk in patients of European descent. The rs2042329 risk allele was also related to significantly increased expression levels of CWC27 mRNA and protein in bladder cancer tissues from Chinese patients. Additional functional analyses suggested that CWC27 played an oncogenic role in bladder cancer by inducing cell proliferation and suppressing apoptosis. In conclusion, the identification of a risk-associated locus at 5q12.3 provides new insights into the inherited susceptibility to bladder cancer in Chinese populations and may help to identify high-risk individuals. Cancer Res; 76(11); 3277-84. ©2016 AACR.

Circulating miR-497 and miR-663b in plasma are potential novel biomarkers for bladder cancer.

MicroRNAs (miRNAs), abundant and highly stable in the plasma, have been widely reported. This greatly pursued us to investigate whether plasma miRNAs could be considered as powerful biomarkers for diagnosing bladder cancer (BC). We performed a plasma miRNAs profile with the TaqMan Low Density Array, and a two-phase validation to detect the candidate miRNAs expression by quantitative PCR. The receiver operating characteristic curve (ROC) and the area under curve (AUC) were used to evaluate diagnostic accuracy. A total of eight plasma miRNAs abnormally expressed between BC patients and healthy controls in microarray analysis (i.e., elevated miRNAs for miR-505, miR-363 and miR-663b, and decreased for miR-99a, miR-194, miR-100, miR-497 and miR-1 in BC plasma). In further independent cohorts, miR-497 and miR-663b with significantly differential expression were confirmed. Moreover, the AUC, sensitivity and specificity were raised to 0.711 (95% CI = 0.641-0.780), 69.7% and 69.6%, respectively, when miR-497 and miR-663b were integrated. This is the first study systematically exploring the existence of specific plasma miRNAs as early diagnostic biomarkers for BC in Chinese population; and these findings supported that plasma miR-497 and miR-663b could be promising novel circulating biomarkers in clinical detection of BC.

Association of interleukin-23 receptor gene polymorphisms with risk of bladder cancer in Chinese.

To assess whether polymorphisms of the interleukin-23 receptor (IL23R) gene are associated with bladder transitional cell carcinoma because chronic inflammation contributes to bladder cancer and the IL23R is known to be critically involved in the carcinogenesis of various malignant tumors. 226 patients with bladder cancer and 270 age-matched controls were involved in the study. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. Genotype distribution and allelic frequencies between patients and controls were compared. In all three single nucleotide polymorphisms of IL23R studied, the distribution of genotype and allele frequencies of rs10889677 differed significantly between patients and controls. The frequency of allele C of rs10889677 was significantly increased in cases compared with controls (0.2898 vs. 0.1833, odds ratio 1.818, 95 % confidence interval 1.349-2.449). The result indicates that IL23R may play an important role in the susceptibility of bladder cancer in Chinese population.

TSP-1-1223 A/G Polymorphism as a Potential Predictor of the Recurrence Risk of Bladder Cancer in a Chinese Population

Backgrounds. TSP-1 is a glycoprotein that functions in the biology of bladder cancer. We investigated the relationship between the distribution of TSP-1-1223 A/G polymorphism (rs2169830) and the clinical characteristics of bladder cancer. Materials and Methods. TaqMan assay was performed to determine the genotype of 609 cases and 670 control subjects in a Chinese population. Logistic regression was used to assess the association between the polymorphism and the risk of bladder cancer. Quantitative real-time polymerase chain reaction was performed to determine TSP-1 mRNA expression. Survival curves were generated using the Kaplan-Meier method. Results. No significant differences were detected in the genotype frequencies of healthy control subjects and patients with bladder cancer. By contrast, the time until the first recurrence differed significantly between genotypes (P = 0.017). The expression of TSP-1 mRNA in bladder cancer tissues was lower in patients with an AG genotype than in those with an AA genotype. The lowest expression was observed in patients with a GG genotype. Conclusions. In conclusion, TSP-1-1223 A/G polymorphism may contribute to the recurrence of bladder cancer in Chinese population.

Genetic Polymorphisms of p53 Codon 72 and Bladder Cancer Susceptibility: A Hospital-Based Case–Control Study

p53 is one of the most widely investigated molecular markers in bladder cancer and its polymorphisms have been related to individual cancer risks. The objective of this study was to explore the association of p53 codon 72 polymorphism with susceptibility and clinicopathologic characteristics of bladder cancer in a Chinese population. We investigated the impact of p53 codon 72 polymorphism in a hospital-based case-control study of bladder cancer. We tested peripheral blood samples from 120 patients with bladder cancer and 120 healthy individuals of similar age and from the same geographical region. The polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay. There was an association between smoking status and bladder cancer (odds ratio [OR] = 2.25; 95% confidence interval [95% CI] = 1.31, 3.87; p = 0.003). Patients with bladder cancer had a significantly lower frequency of Arg/Arg (OR = 0.53; 95% CI = 0.31, 0.89; p = 0.02) and Arg allele (OR = 0.66; 95% CI = 0.45, 0.95; p = 0.03) than controls. Patients with invasive bladder cancer had a significantly lower frequency of Arg/Arg (OR = 0.29; 95% CI = 0.10, 0.88; p = 0.03) than those with superficial bladder cancer. When stratifying by the grade and histological type of bladder cancer, we found no statistical association. These data suggest that the p53 codon 72 Arg/Arg genotype and Arg allele are associated with a lower risk of bladder cancer in Chinese population.

Cyclin D1 G870A Polymorphism Is Associated with Risk and Clinicopathologic Characteristics of Bladder Cancer

Cyclin D1 (CCND1) is a key protein in regulation of cell cycle at the G1-to-S transition phase and is essential for regulation of cell proliferation, differentiation, and transcriptional control. We hypothesized that the CCND1 G870A polymorphism is associated with risk of bladder cancer. The CCND1 G870A polymorphism was genotyped in a hospital-based case-control study of 402 bladder cancer cases and 402 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method. Unconditional univariate and multivariate logistic regression analyses were used to evaluate the associations between the CCND1 G870A polymorphism and bladder cancer risk. A significantly increased risk of bladder cancer was associated with the combined variant CCND1 870GA/AA genotypes (adjusted odds ratio, 1.54; 95% confidence interval, 1.08-2.20) compared with the GG genotype, particularly among subgroups of age ≥65 years (1.74; 1.06-2.88), men (1.67; 1.15-2.44), and smokers (1.82; 1.12-2.93). Further, the G870A polymorphism was significantly associated with risk of developing superficial bladder cancer (grade 1). In addition, a meta-analysis of the G870A polymorphism and bladder cancer risk showed that the variant 870GA/AA genotypes were associated with an increased risk of bladder cancer in Asians, but not in Caucasians, which was consistent with the results of our study. The CCND1 G870A polymorphism may be a marker for the development of bladder cancer in Chinese populations. Larger studies are required to validate these findings in diverse populations.

Genetic variation in PSCA and bladder cancer susceptibility in a Chinese population

Recently, two genome-wide association studies identified a significant association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and risk of diffuse-type of gastric cancer in Asians and bladder cancer in Caucasians, respectively. PSCA has been reported highly expressed in bladder cancer and been considered as a useful marker for diagnosis and progression of bladder cancer. To determine whether rs2294008 polymorphism is associated with risk of bladder cancer in Chinese populations, we conducted a hospital-based case-control study of 581 cases and 580 controls. Sixteen normal bladder tissues adjacent to tumors were used to evaluate the functionality of this polymorphism. We genotyped the rs2294008 polymorphism and assessed its association with risk of bladder cancer and messenger RNA (mRNA) expression in normal bladder tissues. A significant increased risk of bladder cancer was found for rs2294008 CT/TT genotypes (adjusted odds ratio, 1.38; 95% confidence interval, 1.09-1.75) compared with the CC genotype. Furthermore, analysis of PSCA mRNA expression identified a clear correlation of rs2294008 with expression levels of PSCA mRNA. These results indicated that the rs2294008 polymorphism of PSCA gene may play a role in bladder cancer carcinogenesis and it could be served as a biomarker for genetic susceptibility to bladder cancer in Chinese populations.

Common genetic variants on 8q24 contribute to susceptibility to bladder cancer in a Chinese population

A recent genome-wide association study identified two common variants that confer susceptibility to bladder cancer. We hypothesized that these variants are associated with risk of bladder cancer in Chinese populations. We genotyped rs9642880 G>T on 8q24 and rs710521 A>G on 3q28 in a two-stage case-control study of bladder cancer to evaluate the association and further examined the expression of MYC. We found that the rs9642880 G>T, but not the rs710521 A>G polymorphism, was associated with an increased risk of bladder cancer. Compared with the rs9642880 GG genotype, the GT/TT genotypes were associated with an odds ratio of 1.65 (95% confidence interval = 1.25-2.17), and this risk was more pronounced in young men and for low-risk tumors. Additional experiments revealed that the rs9642880 GT/TT genotypes were associated with enhanced levels of both MYC mRNA and protein in bladder tissues. Our findings suggested that the rs9642880 G>T polymorphism on 8q24 was independently associated with the risk of bladder cancer in Chinese populations.

A Six-Nucleotide Insertion-Deletion Polymorphism in the CASP8 Promoter Associated with Risk and Progression of Bladder Cancer

Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. We hypothesized that the variants in the CASP8 gene are associated with risk of bladder cancer. In a hospital-based case-control study of 365 case patients with newly diagnosed bladder transitional cell carcinoma and 368 cancer-free controls frequency-matched by age and sex, we genotyped the functional -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 and assessed its associations with risk of bladder cancer and interaction with tobacco smoking. A significant decreased risk of bladder cancer was found for the CASP8 -652 6N ins/del (adjusted odds ratio, 0.72; 95% confidence interval, 0.53-0.99) and del/del (odds ratio, 0.37; 95% confidence interval, 0.18-0.77) genotypes. Furthermore, a significant additive interaction between CASP8 polymorphism and tobacco smoking on bladder cancer risk was observed. These results suggested that the CASP8 -652 6N ins/del polymorphism is involved in etiology of bladder cancer and thus may be a marker for genetic susceptibility to bladder cancer in Chinese populations. Larger studies are warranted to validate our findings.

A Novel Functional Polymorphism C1797G in the MDM2 Promoter Is Associated with Risk of Bladder Cancer in a Chinese Population

MDM2 is believed to regulate the p53 level in modulating DNA repair, cell cycle control, cell growth, and apoptosis. We hypothesize that genetic variants in the MDM2 gene are associated with risk of bladder cancer. We first conducted a case-control study of 234 bladder cancer cases and 253 cancer-free controls, using the haplotype-based tagging single nucleotide polymorphism (SNP) approach involving 13 common SNPs initially identified in 100 control subjects. We then examined the functionality of the important SNP. We found that the C1797G polymorphism in the MDM2 promoter region is an important SNP because its homozygous variant genotype, but none of the haplotypes, was associated with risk of bladder cancer. Electrophoretic mobility shift assay indicated that the 1797C to 1797G transition within the CAAT/enhancer binding protein alpha (C/EBP alpha) core sequence greatly enhanced the C/EBP alpha binding affinity to the promoter region. The in vitro luciferase assays in various cell lines further showed an increased transcriptional activity of the 1797G allele compared with the 1797C allele. Additional experiments with tumor tissues revealed that the transcriptional activator C/EBP alpha containing the 1797G allele increased levels of the MDM2 mRNA and protein in bladder tumor tissues. These data suggested that the novel MDM2 promoter C1797G polymorphism may affect the MDM2 activity by altering the C/EBP alpha binding affinity to the promoter and, thus, may be a marker for genetic susceptibility to bladder cancer in Chinese populations. Further validation of the functionality of the MDM2 C1797G polymorphism and its association with risk of bladder and other cancers in other ethnic populations is warranted.

Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population

To investigate the association between cytochrome P450 2C19 (CYP2C19) gene polymorphism and cancer susceptibility by genotyping of CYP2C19 poor metabolizers (PMs) in cancer patients. One hundred and thirty-five cases of esophagus cancer, 148 cases of stomach cancer, 212 cases of lung cancer, 112 cases of bladder cancer and 372 controls were genotyped by allele specific amplification-polymerase chain reaction (ASA-PCR) for CYP2C19 PMs. The frequencies of PMs in cancer groups and control group were compared. The frequencies of PMs of CYP2C19 were 34.1%(46/135) in the group of esophagus cancer patients, 31.8%(47/148) in the stomach cancer patients, 34.4%(73/212) in the group of lung cancer patients, only 4.5%(5/112) in the bladder cancer patients and 14.0%(52/372) in control group. There were statistical differences between the cancer groups and control group (esophagus cancer, chi(2)=25.65, P<0.005, OR=3.18, 95%CI=2.005-5.042; stomach cancer, chi(2)=21.70, P<0.005, OR=2.86, 95%CI=1.820-4.501; lung cancer, chi(2)=33.58, P<0.005, OR=3.23, 95%CI=1.503-6.906; bladder cancer, chi(2)=7.50, P<0.01, OR=0.288, 95%CI=0.112-0.740). CYP2C19 PMs have a high incidence of esophagus cancer, stomach cancer and lung cancer, conversely they have a low incidence of bladder cancer. It suggests that CYP2C19 may participate in the activation of procarcinogen of esophagus cancer, stomach cancer and lung cancer, but may involve in the detoxification of carcinogens of bladder cancer.