Cancer In Chinese Han Population Research Articles

RTN4 3'-UTR insertion/deletion polymorphism and susceptibility to non-small cell lung cancer in Chinese Han population.

Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

Association of XRCC1 gene polymorphisms with susceptibility to gastric cancer in Chinese Han population.

Gastric cancer is one of the most frequently causing cancer-related deaths worldwide. The X-ray repair complementing group 1 gene (XRCC1) is an important candidate gene for influencing gastric cancer risk. This study aimed to evaluate the associations between XRCC1 genetic variants and gastric cancer susceptibility in Chinese Han population. Four hundred twenty-four gastric cancer patients and 430 cancer-free controls were enrolled. Two genetic variants (c.1254C>T and c.1779C>G) of XRCC1 gene were genotyped by created restriction site-polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. Results from this study indicated that the allele and genotype frequencies of these two genetic variants were statistically different between gastric cancer patients and cancer-free controls. The association analyses suggested that these two genetic variants were statistically associated with the increased risk of gastric cancer (for c.1254C>T, T versus C: odds ratio (OR) = 1.44, 95% confidence interval (CI) 1.17-1.77; for c.1779C>G, G versus C: OR = 1.51, 95% CI 1.22-1.86). The allele-T of c.1254C>T and allele-G c.1779C>G genetic variants may contribute to the susceptibility to gastric cancer in Chinese Han population. Our data suggest that these two genetic variants might be used as molecular markers for evaluating the susceptibility to gastric cancer.

Tumor Necrosis Factor-Related Apoptosis Inducing Ligand Gene Polymorphisms are Correlated with Gastric Cancer in Central China

To investigate the association of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) gene polymorphisms with gastric cancer in Chinese Han population in central China. A total of 304 patients with gastric cancer confirmed by histopathology and 421 unrelated healthy controls were studied. Gene polymorphisms of TRAIL (G1525A and C1595T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The frequency of the genotype carriers of TRAIL 1525A (GA + AA) and 1595T (CT + TT) was significantly lower in gastric cancer than in healthy controls (37.2% vs. 61.5%, P < 0.001, OR = 0.581, 95% CI 0.442 ~ 0.764; 36.2% vs. 62.0%, P < 0.001, OR = 0.570, 95% CI 0.433 ~ 0.750, respectively). Stratification analysis showed that both TRAIL 1525A (GA + AA) and 1595T (CT + TT) carriers were associated with poorly-differentiated gastric cancer compared to 1525GG genotype and 1595CC genotype (OR = 0.516, 95%CI 0.279 ~ 0.957, P = 0.026; OR = 0.395, 95%CI 0.207 ~ 0.753, P = 0.004, respectively). TRAIL G1525A and C1595T gene polymorphisms were significantly correlated with the susceptibility to gastric cancer in Chinese Han population in central China.

TGF-α gene variations and increased susceptibility of gastric cancer in an eastern Chinese Han population

Transforming growth factor-alpha (TGF-α) correlates with deep invasion, advanced stage and poor prognosis in gastric cancer. Genetic variants in the 3′ untranslated region (UTR) of TGF-α gene may influence the stability and post-transcriptional regulation of mRNA and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped five polymorphisms in 3′UTR (rs3771527, rs503314, rs473698, rs3732253 and rs538118) and one in 3′ near region (rs11466306) of the TGF-α gene by polymerase chain reaction-ligation detection reaction methods (PCR-LDR). We found that GA/AA genotype of rs11466306 in the 3′ near gene could increase the risk of overall gastric cancer (adjusted OR = 1.499, 95%CI: 1.101–2.041), compared to the wild homozygous GG genotype. Meanwhile, the risk effect was more obvious in the intestinal gastric cancer and gastric noncardia cancer (adjusted OR = 1.682, 95%CI: 1.188–2.380; adjusted OR = 1.495, 95%CI: 1.072–2.086, respectively), but not for the diffuse type and gastric cardia cancer (p > 0.05). CT/TT genotype for rs3732253 in the 3′ UTR was associated with increased risk of intestinal gastric cancer (adjusted OR = 1.464, 95%CI: 1.036–2.069), compared to their wild homozygous genotypes. These findings indicate that potentially functional TGF-α gene variant may contribute to the risk of intestinal gastric cancer and/or gastric noncardia cancer and could be used as molecular markers for detecting intestinal gastric cancer and/or gastric noncardia cancer in Chinese Han population.

Association between glutathione S-transferase M1 null variant and risk of bladder cancer in Chinese Han population

Glutathione S-transferase M1 (GSTM1) is one of the most important families of phase II isoenzymes known to detoxify a variety of electrophilic compounds and carcinogens. The GSTM1 null variant is associated with decreased enzyme activity, and it has been assumed to be associated with bladder cancer. The association between the GSTM1 null variant and bladder cancer in the Chinese Han population was unclear owing to the obvious inconsistency from published studies. To quantify the association between the GSTM1 null variant and bladder cancer in the Chinese Han population, we carried out the meta-analysis. We estimated the pooled odds ratio (OR) with its 95% confidence interval (95% CI) to assess the association. Eight studies with a total of 3,887 individuals were finally included into the meta-analysis. Overall, there was an obvious association between the GSTM1 null variant and risk of bladder cancer in the Chinese Han population (OR = 1.61, 95% CI 1.41–1.84, P < 0.001). There was no heterogeneity across those eight studies (I 2 = 0%). The cumulative meta-analyses showed a trend of more obvious association between the GSTM1 null variant and risk of bladder cancer in the Chinese Han population as data accumulated by year. There was no obvious evidence of publication bias in the meta-analysis. In conclusion, the GSTM1 null variant is significantly associated with risk of bladder cancer in the Chinese Han population.

Genetic polymorphisms of XRCC1 gene and susceptibility to gastric cancer in Chinese Han population

This study aims to evaluate whether the c.1471G > A and c.1686C > G genetic polymorphisms of XRCC1 gene influencing gastric cancer susceptibility. A total of 813 subjects with Chinese Han ethnicity were enrolled. Our data suggest that the allele and genotype frequencies are significantly different from gastric cancer patients with cancer-free controls. We find that c.1471G > A and c.1686C > G genetic polymorphisms statistically increase the risk of gastric cancer. Our findings indicate these two genetic polymorphisms are related with the susceptibility to gastric cancer, and could be used as molecular markers for detecting gastric cancer in Chinese Han ethnicity.

Association between single genetic polymorphisms of MDR1 gene and gastric cancer susceptibility in Chinese

Gastric cancer is a common cancer worldwide. The multidrug resistance 1 gene (MDR1) is one of the most important candidate genes for influencing gastric cancer susceptibility. This study aimed to analyze the association between genetic variants of MDR1 gene and the susceptibility to gastric cancer in Chinese Han population. A total of 365 gastric cancer patients and 367 cancer-free controls were enrolled in this study. The single genetic polymorphisms (SNPs) of MDR1 gene were genotyped by the created restriction site-polymerase chain reaction method. Our data suggested that the allele and genotype frequencies of c.159G > T and c.1564A > T were statistically different between gastric cancer patients and cancer-free controls. Association analyses indicated that these two SNPs were statistically associated with the increased risk of gastric cancer (for c.159G > T, TT versus (vs.) GG: OR 2.34, 95 % CI 1.31-4.19; TT vs. OR 2.32, 95 % CI 1.32-4.08; T vs. G: OR 1.27, 95 % CI 1.01-1.59; for c.1564A > T, TT vs. AA: OR 2.27, 95 % CI 1.31-3.93; TT vs. OR 2.21, 95 % CI 1.30-3.75; T vs. A: OR 1.30, 95 % CI 1.04-1.62). The allele-T of both these two SNPs may contribute to the susceptibility to gastric cancer in Chinese Han population. The c.159G > T and c.1564A > T genetic variants might be used as molecular markers for detecting gastric cancer susceptibility.

X-ray repair cross-complementing group 1 Arg194Trp polymorphism is associated with increased risk of lung cancer in Chinese Han population

There were many studies performed to assess the association between X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp polymorphism and lung cancer risk in Chinese Han population, but contradictory results were reported. To provide a comprehensive and objective assessment of the association, a meta-analysis of all eligible case-control studies was carried out. After searching the databases and reading the abstracts, 12 case-control studies on the association between XRCC1 Arg194Trp polymorphism and lung cancer risk were finally included into this meta-analysis. Those 12 studies included a total of 4,385 cases and 4,545 controls. XRCC1 Arg194Trp polymorphism was associated with increased risk of lung cancer in Chinese Han population under three main models (allele contrast model, odds ratio (OR) = 1.12, 95 % confidence interval (CI) 1.00-1.26, P = 0.049; homozygote model, OR = 1.27, 95 % CI 1.09-1.48, P = 0.003; recessive model, OR = 1.26, 95 % CI 1.09-1.46, P = 0.003). However, there was no obvious association between XRCC1 Arg194Trp polymorphism and lung cancer risk under the dominant model (OR = 1.06, 95 % CI 0.98-1.16, P = 0.146). Sensitivity analysis suggested the stability and liability of this meta-analysis. Therefore, this meta-analysis suggests that XRCC1 Arg194Trp polymorphism is associated with increased risk of lung cancer in Chinese Han population.

Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population

Previous investigations indicated that histamine receptor H4 (HRH4) played important roles in many aspects of breast cancer pathogenesis, and that the polymorphisms of HRH4 gene may result in expression and functional changes of HRH4 proteins. However, the relationship between polymorphisms of HRH4 and breast cancer risk and malignant degree is unclear. In the present study, we conducted a case–control investigation among 185 Chinese Han breast cancer patients and 199 ethnicity-matched health controls. Four tag-SNPs (i.e. rs623590, rs16940762, rs11662595 and rs1421125) of HRH4 were genotyped and association analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the association. We found that the T allele of rs623590 had a decreased risk of breast cancer (adjusted OR, 0.667; 95% CI, 0.486–0.913; P=0.012) while the A allele of rs1421125 had an increased risk (adjusted OR, 1.653; 95% CI, 1.139–2.397; P=0.008). Further haplotype analysis showed that the CAA haplotype of rs623590–rs11662595–rs1421125 was more frequent among patients with breast cancer (adjusted OR, 1.856; 95% CI, 1.236–2.787; P=0.003). Additionally, polymorphisms of rs623590 and rs11662595 were also correlated with clinical stages, lymph node involvement, and HER2 status. These findings indicated that the variants of rs623590, rs11662595 and rs1421125 genotypes of HRH4 gene were significantly associated with the risk and malignant degree of breast cancer in Chinese Han populations, which may provide us novel insight into the pathogenesis of breast cancer although further studies with larger participants worldwide are still needed for conclusion validation.

Significant association of 5p15.33 (TERT–CLPTM1L genes) with lung cancer in Chinese Han population

ABSTRACTLung cancer is a leading cause of cancer-related deaths throughout the world. Recent genome-wide association studies and consecutive validation supported that the 5p15.33 region containing telomerase reverse transcriptase gene (TERT) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) gene showed significant association with lung cancer in multiple populations. Here we studied a large Chinese Han cohort consisting of 1759 cases and 1804 controls. In the 1st stage (784 cases versus 782 controls) we genotyped 13 tag SNPs within 5p15.33 region to further investigate the association. After the 2nd stage validation (975 cases versus 1022 controls), the study clarified the association that rs2736100 of the TERT gene conferred the highest significant risk of lung cancer (P = 4 × 10−3 in the 1st stage association, P = 4 × 10−4 in the 2nd stage validation, and P = 1 × 10−5, odds ratio = 1.24 in the combined population). The results provided the evidence of a cross-race susceptibility of the lung cancer locus.

Progress in research of polymorphisms of genes associated with susceptibility to esophageal cancer in Chinese Han population

Progress in research of polymorphisms of genes associated with susceptibility to esophageal cancer in Chinese Han population

Association of the Polymorphism of APE1 Gene with the Risk of Prostate Cancer in Chinese Han Population

DNA damage, caused by numerous carcinogens, contributes to the increased risk of different types of cancer. The base excision repair (BER) pathway including the apurinic/apyrimidic endonuclease (APE1, also known as APEX1) gene plays an important role in preventing the accumulation of DNA damage and maintaining genomic stability. The aim of the present study is to determine whether polymorphisms of APE1 are associated with the risk of prostate cancer (PCa) in the Chinese Han population. This study consisted of 198 patients with PCa and 156 healthy controls. The polymorphisms of APE1, Asp148Glu (rs1130409) and -141T/G (rs1760944) were determined by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The genotypic distributions of the two polymorphisms in controls were in Hardy-Weinberg equilibrium (p = 0.92 and p = 0.83, respectively). Logistic regression analysis indicated that the -141GG genotype was significantly associated with a decreased risk of PCa compared with the -141TT genotype (p = 0.03; OR 0.49; 95% CI 0.26 - 0.92). The G allele was also significantly associated with a reduced risk of PCa compared with the T allele (p = 0.02; OR 0.71; 95% CI 0.52 - 0.96). However, no association between Asp148Glu polymorphism and the risk of PCa was found. The -141GG genotype and G allele of the APE1 gene are associated with a decreased risk of PCa in the Chinese Han population.

RASSF1A Promoter Methylation as a Candidate Biomarker for the Early Detection of Lung Cancer in Chinese Han Population

RASSF1A Promoter Methylation as a Candidate Biomarker for the Early Detection of Lung Cancer in Chinese Han Population

Association of Genetic Polymorphisms in the Paraoxonase 1 Gene With the Risk and Prognosis of Non–Small Cell Lung Cancer in Chinese Han Population

ObjectiveOxidative stress and free radicals have been indicated to be associated with increased risk of various cancers. Paraoxonase 1 (PON1) gene, encoding PON1 protein, plays an important role as an...

Association of MHC class-III gene polymorphisms with ER-positive breast cancer in Chinese Han population

Polymorphisms of the major histocompatibility complex (MHC) have been linked to many diseases, especially autoimmune disorders. Previous studies have shown that genetic variants in MHC class III are associated with breast cancer. To determine if there is an association between MHC class III and breast cancer risk in the Chinese Han population, we carried out a hospital-based case-control study in Guangdong and Jiangsu Provinces, including 216 histologically confirmed breast cancer patients and 216 healthy controls. Nine SNP markers distributed in the class III-coding region were detected using the Sequenom MassARRAY(®) iPLEX System. Deviation from Hardy-Weinberg equilibrium was observed for seven SNPs. There was no significant association between these seven SNP variants and breast cancer in these Chinese women (unconditional logistic regression analysis). However, chr6_31697494 at BAT2, one of the seven SNPs, was found to be significantly associated with both ER- and PR-positive breast cancer. In addition, both chr6_31911109 at C6orf48 and chr6_31975605 at ZBTB12, another two of the seven SNPs, show relevance with ER-positive breast cancer. In conclusion, this is the first evidence that genetic polymorphisms in the MHC class III region are significantly associated with ER-positive breast cancer in the Han Chinese population.

6025 POSTER Association Between ESR1 and ESR2 Polymorphisms and Risk of Colorectal Cancer in Chinese Han Population

6025 POSTER Association Between ESR1 and ESR2 Polymorphisms and Risk of Colorectal Cancer in Chinese Han Population

The Ku70 −1310C/G promoter polymorphism is associated with breast cancer susceptibility in Chinese Han population

Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based case-control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437) of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 -1310C/G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A significant difference in genotype distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of breast cancer compared with the CC homozygotes (OR=1.43, 95% CI=1.02-2.00, P=0.038 and OR=3.53, 95% CI=1.60-7.80, P=0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast cancer among premenopausal women (OR=1.68, 95% CI=1.21-2.33, P=0.002), but not in postmenopausal women (OR=1.33, 5% CI=0.85-2.10, P=0.216). Our study suggests that the Ku70 -1310C/G promoter polymorphism may be a susceptibility factor for breast cancer in Chinese Han population.

Association of CASP3 polymorphisms and its haplotypes with susceptibility of breast cancer

To investigate the association of Caspase3 (CASP3) polymorphisms with susceptibility of breast cancer in Chinese Han population. In this population-based case-control study, 251 cases with breast cancers and 251 matched controls in terms of habitation and age (±5 years) were recruited. Rs4647693, rs2696056, rs4647610 were selected as TagSNPs in CASP3 gene and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The haplotype distribution was estimated and compared by PHASE software. There was significant association between menarche age and breast cancer (P=0.007), as well as the early pregnancy age and breast cancer (P=0.002). No significant differences were detected in the distribution of CASP3 genotype and haplotype frequencies between breast cancer patients and controls. The GGA was the most common haplotype both in cases and controls. CASP3 polymorphisms and its haplotypes were not related to the susceptibility of breast cancer.

PD-1 polymorphisms are associated with sporadic breast cancer in Chinese Han population of Northeast China

The programmed death-1 (PD-1) is a potent immunoregulatory molecule which is responsible for the negative regulation of T-cell activation and peripheral tolerance. In order to investigate the association between polymorphisms of PD-1 and breast cancer, a case-control study was conducted in Chinese female population consisting of 490 cases with breast cancer and 512 age-matched healthy individuals from Heilongjiang Province of China. Four polymorphisms of the PD-1 gene, including rs36084323 (PD-1.1), rs7421861, rs2227982 (PD-1.9), and rs2227981 (PD-1.5), were selected and genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of PD-1.1 GG genotype and PD-1.5 CT genotype were significantly lower in cases compared with controls (P = 0.020 and 0.004, respectively), and PD-1.5 CC genotype and C allele had higher frequencies in cases (P = 0.003 and 0.010). In haplotype analysis, we observed that the frequencies of ATTC and GTCT haplotypes were lower in cases than those of in controls (P = 0.0055 and 0.0012, respectively), whereas the GTCC and ATCC haplotypes had higher frequencies in cases (P = 0.0040 and 0.00008037, respectively). Additionally, strong association was showed between PD-1.1 and P53, and haplotype CCTA was associated with ER status. These results primarily suggest that PD-1 gene polymorphisms may affect the breast cancer risk and prognosis in Chinese Han females of Heilongjiang Province in Northeast China.

Mn-SOD and CuZn-SOD polymorphisms and interactions with risk factors in gastric cancer.

To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557, rs4880), Helicobacter pylori (H. pylori) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD2-16Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD2-16Ala/- genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/- genotype, SOD2-16Ala/- genotype, alcohol drinking, positive family history and type I H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/- genotype and SOD2-16Ala/- genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). SOD1-7958A/- and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.