Cancer In Chinese Han Population Research Articles

Rs12537 Is a Novel Susceptibility SNP Associated With Estrogen Receptor Positive Breast Cancer in Chinese Han Population

Genetic testing is widely used in breast cancer and has identified a lot of susceptibility genes and single nucleotide polymorphisms (SNPs). However, for many SNPs, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are not in place. A recent genome-wide long non-coding RNA (lncRNA) association study in Chinese Han has verified a genetic association between rs12537 and breast cancer. This study is aimed at investigating the association between rs12537 and the phenotype. We collected the clinical information of 5,634 breast cancer patients and 6,308 healthy controls in the early study. And χ2 test was used for the comparison between different groups in genotype. The frequency of genotypic distribution among SNP rs12537 has no statistically significant correlation with family history (p = 0.8945), menopausal status (p = 0.3245) or HER-2 (p = 0.2987), but it is statistically and significantly correlated with ER (p = 0.004006) and PR (p = 0.01379). Most importantly, compared to the healthy control, rs12537 variant is significantly correlated with ER positive patients and the p-value has reached the level of the whole genome (p = 1.66E-08 <5.00E-08). Furthermore, we found rs12537 associated gene MTMR3 was lower expressed in breast cancer tissues but highly methylated. In conclusion, our findings indicate that rs12537 is a novel susceptibility gene in ER positive breast cancer in Chinese Han population and it may influence the methylation of MTMR3.

Association of ERBB4 genetic polymorphism with the risk and prognosis of non-small cell lung cancer in Chinese Han population: A population-based case-control study.

The aim of this study was to explore the association of rs1836724 single-nucleotide polymorphism (SNP) of ERBB4 with risk and prognosis of non-small cell lung cancer (NSCLC) in the Chinese Han population.The genotype of rs1836724 SNP of ERBB4 from 258 patients with NSCLC and 200 noncancer controls were detected the TaqMan-MGB probes real-time fluorescence polymerase chain reaction. The distribution of genotype and alleles between the 2 groups was compared, and the association between clinicopathological characteristic and rs1836724 SNP was analyzed. Prognosis and influencing factors were analyzed by Kaplan-Meier and Cox regression analysis.There were significant differences in the genotype and allele distribution of ERBB4 rs1836724 between the NSCLC group and control group (P < .05). And CC genotype of rs1836724 was associated with increased risk of NSCLC in the Chinese Han population. Rs1836724 SNP was associated with TNM stage and lymph nodal metastasis (P = .001, P = .007). The median follow-up was 29 months, and the progression-free survival and overall survival of 258 NSCLC patients were 27.91% and 31.39%, respectively. Patients with GG genotype of rs1836724 had poor progression-free survival and overall survival. Rs1836724 SNP was an independent prognostic marker of NSCLC patients, CC genotype had a high risk of poor prognosis (odds ratio = 1.587, 95% confidence interval: 1.079–2.335, P = .019).In Chinese Han populations, rs1836724 SNP of ERBB4 may contribute toward the increased risk and poor prognosis of NSCLC.

Association of Long Non-Coding RNA MEG3 Polymorphisms and Risk of Prostate Cancer in Chinese Han Population.

To explore the association between MEG3 polymorphisms and the risk of prostate cancer in the Chinese Han population. Two MEG3 single-nucleotide polymorphisms (SNPs) (rs11627993 C >T rs7158663 A>G) were genotyped in a case-control study in which 165 prostate cancer patients and 200 healthy controls were recruited by a Real-Time Polymerase Chain Reaction (PCR) with the TaqMan assay. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of association. No statistically significant differences were found in the allele or genotype distributions of the MEG3 rs11627993 C >T and rs7158663 A > G polymorphisms among cases or healthy control subjects (rs11627993: CC vs CA: 95% CI = 0.54-1.95, ORs = 1.03; CC vs AA: 95% CI = 0.67-2.54, ORs = 1.30 ; CC/CA vs AA: 95% CI = 0.81-1.98, ORs = 1.26 , P = .29 ; C vs A: 95% CI = 0.85-1.57, ORs = 1.16, P = .35; rs7158663: AA vs AG: 95% CI = 0.76-5.08, ORs = 1.97, AA vs GG: 95% CI = 0.57-3.29, ORs = 1.37; AA/AG vs GG : 95% CI = 0.56-1.32, ORs = 0.86, P = .49; A vs G: 95% CI = 0.69-1.39, ORs = 0.98, P = .91) Further stratified analysis detected no significant association. The MEG3 polymorphisms (rs11627993 C>T and rs7158663 A>G) does not influence the susceptibility to prostate cancer.

MiR-143HG Gene Polymorphisms as Risk Factors for Gastric Cancer in Chinese Han Population.

MicroRNA (miRNA) is a pivotal regulator of the occurrence and development of various cancers. And gastric cancer (GC) is one of the most common and deadly cancers in the world. The aim of this study is to explore whether the microRNA-143 host gene (miR-143HG) polymorphisms are correlated with the risk of GC. 5 single-nucleotide polymorphisms (SNPs) were genotyped among 506 patients and 500 healthy controls in Han Chinese population. Multiple genetic models, stratification analysis and haplotype analysis were used to evaluate the association between miR-143HG polymorphisms and GC risk by calculating odds ratios (ORs), 95% confidence intervals (CIs). Our results indicated that rs11168100 was associated with decreased risk of GC under the Codominant model (OR = 0.67, 95%CI = 0.52-0.88, p = 0.003), and under the Dominant model (OR = 0.72, 95%CI = 0.56-0.92, p = 0.009). Rs353300 was associated with increased risk of GC under the Recessive model (OR = 1.41, 95%CI = 1.06-1.87, p = 0.017). Further, rs11168100 and rs353300 were correlated with the susceptibility of GC (age > 60 years), and three SNPs (rs12654195, rs353303, and rs353300) were related with the risk of GC (age ≤ 60 years). In addition, two SNPs (rs12654195 and rs11168100) were found to be associated with decrease in the susceptibility of GC in the female subgroup. Rs353300 represented two-sided roles in the occurrence and development of GC in female. Finally, rs3533003 was associated with decreased risk of GC in stratified analysis of lymph node metastasis. For the first time, our results provide some evidence on the polymorphisms of miR-143HG associated with GC risk in the Chinese Han population.

Impact of IL1R1 polymorphisms on the risk of head and neck cancer in Chinese Han population.

The incidence of head and neck cancer (HNC) is increasing but its pathogenic factors are complex. Changes in both internal (genetic) and external (environmental) causes HNC to some extent. The purpose of our study was to investigate the influence of IL1R1 polymorphisms on HNC risk in Chinese Han population. Genotypes of 535 HNC patients and 538 healthy controls were analyzed by Agena MassARRAY. Odds ratio (ORs) and 95% confidence interval (CIs) were calculated by logistic regression analysis to evaluate the relationship between single nucleotide polymorphisms (SNPs) and HNC susceptibility. It was found that the rs956730 of IL1R1 reduced the risk of HNC in multiple models (allele: OR=0.76, 95% CI: 0.62-0.93, p=0.008; codominant: OR=0.43, 95% CI: 0.25-0.75, p=0.003; recessive: OR=0.45, 95% CI: 0.26-0.77, p=0.004; additive: OR=0.77, 95% CI: 0.63-0.94, p=0.01). IL1R1 rs956730 had a protective effect on HNC at age≤46. However, the rs3917225 increased a 1.31-fold HNC risk in the codominant model (OR=1.31, 95% CI: 1.00-1.70, p=0.03). Our study showed that the rs956730 of IL1R1 gene in Chinese Han population was associated with a reduced risk of HNC, while the rs3917225 of IL1R1 might increase the risk of HNC.

CYP4F2 and CYP3A5 gene polymorphisms and lung cancer in Chinese Han population

This study aimed to explore whether the polymorphisms of CYP4F2 and CYP3A5 are correlated with the risk of lung cancer development. A case–control study was conducted among 510 patients with pathologically confirmed lung cancer as the case group and 504 healthy individuals as the control group. Four single-nucleotide polymorphisms of the CYP4F2 and CYP3A5 genes were genotyped, and their correlations with the risk of lung cancer were examined using Chi-square test and logistic regression analysis. Stratified analysis found that the rs3093105 and rs3093106 loci of CYP4F2 gene were significantly associated with lower risk of lung cancer (P = 0.012, OR 0.64, 95% CI 0.45–0.91). The correlation was related to patients’ age and sex and pathological type of lung cancer. Similarly, the rs10242455 loci of CYP3A5 gene showed a statistical significance between the case group and the control group (P = 0.018, OR 0.71, 95% CI 0.53–0.94), which also was associated with reduced risk of squamous cell lung cancer in the dominant and additive models (dominant: OR 0.66, 95% CI 0.46–0.94, P = 0.021; additive: OR 0.71, 95% CI 0.53–0.95, P = 0.023). CYP4F2 and CYP3A5 gene polymorphisms are associated with the reduced risk of non-small cell lung cancer, and its correlation is related to patients’ age and sex and pathological type of lung cancer.

MicroRNA Binding Site Polymorphisms of the Long-Chain Noncoding RNA MALAT1 are Associated with Risk and Prognosis of Colorectal Cancer in Chinese Han Population

Background: The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) gene's rs664589 locus is located within the binding site of the miRNA hsa-miR-194-5p for its cognate long-chain noncoding RNA (lncRNA) MALAT1. The aim of this study was to investigate the association between the rs664589 single nucleotide polymorphism (SNP) and the risk and prognosis of colorectal cancer (CRC) in the Chinese Han population. Methods: A cohort of 340 patients with CRC who underwent surgical resection and another group of 340 healthy subjects were enrolled in this study and analyzed for their rs664589 genotypes. In addition, quantitative real-time-polymerase chain reaction was used to detect the expression levels of the lncRNA MALAT1 and the hsa-miR-194-5p in cancer tissues and paracancerous normal tissues of CRC patients. Results: The risk of CRC in subjects carrying the G allele at the rs664589 locus in the 3' untranslated region of the MALAT1 gene was 1.81 times higher than for C allele carriers. The expression levels of the lncRNA MALAT1 in cancer tissues was significantly higher than that in paracancerous tissues, while the hsa-miR-194-5p expression level was significantly lower in cancerous tissues compared to cognate paracancerous tissues. The progression-free survival (PFS) rate for patients with the MALAT1 gene rs664589 locus GG genotype was significantly lower than that of CG genotype patients. Moreover, lncRNA MALAT1 inhibited the expression of hsa-miR-194-5p. Conclusion: The risk of CRC was relatively higher among MALAT1 rs664589 G allele carriers, and the CRC patients with a G allele had a lower PFS. The likely mechanism underlying these observations is that the rs664589 SNP affects the binding efficiency between the lncRNA MALAT1 and the miRNA has-miR-194-5p, although this awaits laboratory confirmation.

APC gene 3'UTR SNPs and interactions with environmental factors are correlated with risk of colorectal cancer in Chinese Han population.

Objective: To study the correlation between adenomatous polyposis coli (APC) gene 3′ untranslated region (UTR) single nucleotide polymorphisms (SNPs) and their interactions with environmental factors and the risk of colorectal cancer (CRC) in a Chinese Han population.Methods: Genotypes of APC gene 3′UTR rs1804197, rs41116, rs448475, and rs397768 loci in 340 Chinese Han patients with CRC and 340 healthy controls were analyzed. All patients with CRC were analyzed for progression-free survival (PFS) during a 3-year follow-up.Results: The risk of CRC in subjects carrying the APC gene rs1804197 A allele was 2.95-times higher than for the C allele carriers. The interactions of the rs1804197 SNP with body mass index (BMI) and smoking were associated with the risk of CRC. The risk of CRC in the APC gene rs397768 G allele carriers was 1.68-times higher than in the A allele carriers. The interaction between the rs397768 locus SNP and gender was also associated with the risk of CRC. The 3-year PFS of patients with APC gene rs1804197 AA genotype, CA genotype, and CC genotype CRC decreased in this order, with significant difference. In addition, the 3-year PFS of rs397768 locus GG genotype, AG genotype, and AA genotype CRC patients decreased in this order, and the difference was significant.Conclusion: The rs1804197 locus in the 3′UTR region of the APC gene and its interactions with BMI and smoking are associated with the risk of CRC in a Chinese Han population. In addition, the interaction between rs397768 locus SNP and gender is related to the risk of CRC.

The influence of ACYP2 polymorphisms on gastrointestinal cancer susceptibility in the Chinese Han population.

BackgroundGastrointestinal cancer (GI cancer) is a type of cancer that has a high death rate. It has been reported that ACYP2 gene was associated with the development of gastric cancer and colorectal cancer, but it is not clear that the relationship between ACYP2 gene and GI cancer in Chinese Han population. This study aimed to investigate the association between polymorphisms of ACYP2 and GI cancer in the Chinese Han population.MethodsWe used Agena MassARRAY to determine the genotypes of 1,160 GI cancer patients and 495 healthy controls. The correlation between ACYP2 variants and GI cancer risk was examined by logistic regression analysis.ResultsWe identified that rs6713088 (OR = 1.17, 95% CI: 1.00–1.36, p = 0.047), rs843711 (OR = 1.17, 95 CI: 1.01–1.36, p = 0.035), and rs11896604 (OR = 1.20, 95% CI: 1.00–1.45, p = 0.048) were correlated with an increased risk of GI cancer under allele model. Rs11125529 under the recessive model (OR = 2.05, 95% CI: 1.00–4.23, p = 0.038), rs843711 in recessive model (OR = 1.37, 95% CI: 1.04–1.82, p = 0.026), and rs11896604 under log‐additive model (OR = 1.23, 95% CI: 1.01–1.51, p = 0.042) were associated with an increased risk of GI cancer.ConclusionOur study suggested that polymorphisms of ACYP2 gene might be associated with susceptibility to GI cancer.

Association between AXIN1 Gene Polymorphisms and Bladder Cancer in Chinese Han Population.

Background Previous evidence has indicated that the reduction of axis inhibition protein 1 (AXIN1) expression is related with the poor differentiation of non-small-cell lung cancer (NSCLC). However, the potential association between AXIN1 and bladder cancer (BC) is unknown. We aimed to initially explore the relevance of AXIN1 gene polymorphisms (rs12921862 C/A, rs1805105 T/C, and rs370681 C/T) and BC. Methods Three hundred and sixteen BC patients and 419 healthy controls had been enrolled. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping three tag single-nucleotide polymorphisms (SNPs) of AXIN1. The SNPstats online analysis software and SPSS software were used for statistical analysis. Results Our data revealed that three tag SNPs were associated with an increased risk of BC (rs12921862: P < 0.001, OR (95%CI) = 4.61 (3.13-6.81); rs1805105: P = 0.046, OR (95%CI) = 1.35 (1.00-1.82); and rs370681: P = 0.004, OR (95%CI) = 1.56 (1.15-2.10)). For rs12921862, A allele was an independently protective factor which correlated with a better prognosis in non-muscle-invasive bladder cancer (NMIBC) patients (P = 0.03, OR (95%CI) = 0.10 (0.01-0.84)). Stratification analysis demonstrated that rs370681 polymorphism was related with high-grade bladder cancer (P = 0.04, OR (95%CI) = 1.85 (1.04-3.23)). Conclusion The AXIN1 gene polymorphisms might implicate in BC risk, and rs12921862 could be a potential forecasting factor for prognosis of BC patients.

IL1A polymorphisms is a risk factor for colorectal cancer in Chinese Han population: a case control study

BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population.MethodsTo evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets.ResultsAfter adjusting for age and gender, the “AA” genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05–3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03–4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13–5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04–4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01–4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs.ConclusionsThis study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.

Relationships of TGFβ1 and TGFβR2 gene polymorphisms with colorectal cancer in Chinese Han population in Shandong area

Objective To study the relationships of TGFβ1 (-509C/T, + 869T/C) and TGFβR2 (-875 G/A) single nucleotide polymorphisms (SNPs) with colorectal cancer (CRC) in Chinese Han population in Shandong. Methods TGFβ1 -509C/T and + 869T/C SNPs in a total of 490 patients with CRC were detected using gene chip. TGFβR2 -875 SNPs was analyzed using PCR-RFLP. TGFβ1 concentrations in serum samples were measured by ELISA. Immunohistochemistry was used to detect the expression of TGFβR2. The relationships of TGFβ1 (-509C/T, + 869T/C) and TGFβR2 (-875 G/A) SNPs with CRC were analyzed through a case-control study. Chi-square test or t test was used for statistical analysis. Relative risk was estimated by odds ratio (OR) and 95% confidence interval (95%CI). Results No significant difference in genotype or allele frequency at TGFβ1 -509/+ 869 was found between patients with CRC and healthy subjects (P>0.05). The frequencies of TGFβR2 -875GG genotype and -875G allele in patients with CRC were significantly higher than those in healthy subjects (-875GG: χ2=4.65, P=0.031, OR=1.32, 95%CI=1.03-1.71; -875G: χ2=4.95, P=0.026, OR=1.29, 95%CI=1.03-1.61). Compare with the healthy control group, higher frequencies of TGFβR2 -875GG genotype and -875G allele were also detected in rectal cancer (-875GG: P=0.04, OR=1.39, 95%CI=1.02-1.95 and -875G: P=0.045, OR=1.32, 95%CI=1.01-1.73), tubular adenocarcinoma (-875GG: P=0.004, OR=1.51, 95%CI=1.14-2.00 and -875G: P=0.003, OR=1.45, 95%CI=1.14-1.85) and highly differentiated tubular adenocarcinoma (-875GG: P=0.003, OR=1.68, 95%CI=1.19-2.38 and -875G: P=0.002, OR=1.62, 95%CI=1.18-2.21) groups. The serum TGFβ1 levels in TGFβR2 -875G carriers with CRC were significantly higher than those in TGFβR2 -875AA carriers in both CRC (t=-3.42, P<0.05) and healthy control (t=-5.09, P<0.001) groups. TGFβR2 expression in -875G carriers with rectal cancer was significantly lower than that in -875AA carriers with rectal cancer (P=0.047) and healthy subjects (P=0.027). Conclusion TGFβR2 -875GG might be a potential risk factor for CRC in Chinese Han population in Shandong and TGFβR2 -875G might be a risk factor for rectal cancer and highly differentiated tubular adenocarcinoma. Key words: Colorectal cancer; TGFβR2; Polymorphism, single nucleotide

Correlations between CYP3A4 polymorphism and susceptibility to breast cancer in Chinese Han population.

CYP3A4 is a major enzyme catalyzing the metabolism of endogenous steroids that play an important role in the etiology of carcinogenesis. This study was designed to investigate the contribution of CYP3A4 polymorphism to breast cancer in Chinese Han female population. To examine whether variants of CYP3A4 contribute to breast cancer, 5 single-nucleotide polymorphisms (SNPs) of CYP3A4 were genotyped by Sequenom MassARRAY in 267 breast cancer patients and 302 healthy controls. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusted for age. We found that the TT genotype of CYP3A4*1G (rs2242480) polymorphism was associated with increased risk of breast cancer using the fixed effects model (recessive model: OR = 2.34, p = 0.018). Stratified according to age, CYP3A4*1G increased the risk of breast cancer especially in less than 50-year-old group (codominant model OR = 3.68, p = 0.041; recessive model: OR = 3.55, p = 0.012). Furthermore, TT genotype of rs2242480 was associated with Cerb-B2 positive (recessive model: OR = 2.47, p = 0.025) and stage I/II (recessive model: OR = 2.32, p = 0.041). However, no statistically significant associations in other polymorphisms and haploview analysis were observed. This study provides an evidence for polymorphism of CYP3A4 gene associated with the development of breast cancer, also a new insight into etiology of breast cancer. However, the underlying mechanism of the CYP3A4 gene in breast cancer is necessary for further study.

Association between Zinc transporter genes ZIP11 rs11077654 polymorphism with bladder cancer risk in Chinese Han Population

ObjectiveTo study the association between Zinc transporter genes ZIP11 rs11077654 polymorphism with bladder cancer risk in Chinese Han Population. MethodsA total of 307 unrelated Chinese Han descent, including 139 bladder cancer patients as bladder cancer group and 168 healthy people as healthy control group were studied. The ZIP11 rs11077654 loci was analyzed by Polymerase Chain Reaction (PCR) and its relationship with bladder cancer was analyzed. ResultsThere were three kinds of genotypes in ZIP11 gene rs11077654 loci (CC, CA and AA). Our analysis presented that the CA genotype was not associated with bladder cancer risk when the CC genotype may be served as reference (OR, 1.355; 95% CI, 0.750–2.451; p = 0.313). We combined CA and AA genotypes as a dominant genetic model. There was no significant association with bladder cancer risk as well in the combined group (OR, 1.333; 95% CI, 0.758–2.343; p = 0.317). There was no significant association observed between the CA/AA genotypes and low-grade (OR, 0.900; 95% CI, 0.411–1.973; p = 0.793) or high-grade bladder cancer (OR, 0.675; 95% CI, 0.349–1.308; p = 0.243), and nor between the CA/AA genotypes and NMIBC (OR, 0.636; 95% CI, 0.334–1.213; p = 0.167) or MIBC (OR, 1.100; 95% CI, 0.478–2.531; p = 0.823). ConclusionThe rs11077654 of ZIP11 gene was not associated with bladder cancer in Chinese Han Population.

Interaction Between XRCC1 Gene Polymorphisms and Obesity on Susceptibility to Papillary Thyroid Cancer in Chinese Han Population

Background/Aims: To investigate the association of several single nucleotide polymorphisms (SNPs) within XRCC gene and additional gene- environment interaction with papillary thyroid cancer (PTC) risk. Methods: Testing for Hardy-Weinberg equilibrium in controls was conducted using SNPstats (online software: http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 5 SNPs within XRCC gene and obesity. Results: Logistic regression analysis showed that the C allele of rs861539 and T allele of rs1799782 were associated with increased PTC risk Adjusted ORs (95%CI) were 1.65 (1.23-2.12) and 1.61 (1.20-2.04). However There was no relation of rs25489 Rs25487 and rs13181 with PTC. The cross-validation consistency and the testing accuracy for each of the models were determined by GMDR analysis. One two-locus model (rs1799782 and obesity) had a testing accuracy of 62.11% Which was significant at the p < 0.01 level. The D’ value between rs1799782 and rs13181 within ERCC1 gene was more than 0.75 (0.825). So haplotype analysis was just conducted for rs1799782 and rs13181 using the SHEsis online haplotype analysis software. In all samples The haplotype C- A was observed most frequently in two groups With 49.46% and 55.79% in the PTC patients and controls Respectively. The results also indicated that haplotype T- C was significantly associated with increased PTC risk. Conclusion: The C allele of rs861539 and T allele of rs1799782 Interaction between rs1799782 and obesity and haplotype T- C were all associated with increased PTC risk.

Association between SNPs in microRNA machinery genes and gastric cancer susceptibility, invasion, and metastasis in Chinese Han population.

ObjectiveThe present study investigates the influence of genetic variants in miRNA machinery genes (DROSHA, DICER, AGO1, and GEMIN4) on gastric cancer in Chinese Han population, further revealing the genetic mechanisms of gastric cancer occurrence and development.MethodsGenotyping of single nucleotide polymorphisms (SNPs) was performed in 628 patients with GC and 502 frequency-matched (age and gender) controls by the high resolution melting (HRM) method.ResultsThe SNPs rs3742330 (DICER) and rs7813 (GEMIN4) were associated with susceptibility to gastric cancer (P = 0.002 and 0.010, respectively). Stratified analysis showed that the G allele of rs3742330 and genotype TT as well as T allele of rs7813 were associated with a later stage of gastric cancer (P=0.027, 0.032 and 0.018, respectively). Furthermore, the genotype TT and T allele of rs7813 appeared to be associated with a higher level of lymphatic metastasis of gastric cancer (P=0.021 and 0.030, respectively), while the genotype AA and A allele of rs636832 (AGO1) were correlated with a lower level of lymphatic metastasis of gastric cancer (P=0.016 and 0.041, respectively). There was no significant association between rs10719 (DROSHA) and gastric cancer.ConclusionThe present data demonstrated that genetic variants in miRNA machinery genes had a significant association with GC susceptibility (DICER and GEMIN4) and malignant behavior such as tumor stage (DICER and GEMIN4) and lymphatic metastasis of GC (GEMIN4 and AGO1) in Chinese Han population.

Investigation of methylenetetrahydrofolate reductase tagging polymorphisms with colorectal cancer in Chinese Han population.

The aim of this case-control study was to assess the relationship between the tagging polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene and the susceptibility to colorectal cancer (CRC) in a Chinese Han population. A custom-by-design 48-Plex SNPscan Kit was used to determine the genotypes of MTHFR rs3753584 T>C, rs9651118 T>C, rs1801133 G>A, rs4846048 A>G and rs4845882 G>A polymorphisms in 387 CRC patients and 1,536 non-cancer controls. The results revealed that MTHFR rs1801133 G>A polymorphism was associated with a decreased risk of overall CRC. While MTHFR rs4845882 G>A polymorphism conferred an increased risk to overall CRC. In a stratified analysis by CRC region, we found MTHFR rs3753584 T>C and rs9651118 T>C polymorphisms were associated with the increased risk of colon cancer. In addition, a significantly increased risk of rectum cancer associated with MTHFR rs3753584 T>C polymorphism was overt. However, MTHFR rs1801133 G>A polymorphism conferred a decreased risk to colon cancer. In conclusion, findings of the present study reveal that the tagging polymorphisms in MTHFR gene (rs3753584 T>C, rs9651118 T>C and rs4845882 G>A) are associated with the increased risk of CRC. However, MTHFR rs1801133 G>A polymorphism confers a decreased risk to CRC. Additional studies with larger sample size are needed to confirm these findings.

Relationship between the TERT, TNIP1 and OBFC1 genetic polymorphisms and susceptibility to colorectal cancer in Chinese Han population.

Colorectal cancer (CRC) is one of the most common diseases worldwide, and telomere length has been reported correlate with CRC. This study aimed to investigate whether polymorphisms of telomere length related genes are associated with susceptibility to CRC in Chinese Han population. 11 SNPs from TERT, TNIP1 and OBFC1 genes were selected and genotyped, in addition odds ratio (OR) and 95% confidence intervals (CI) were used to evaluate association between the SNPs and CRC risk in 247 patients clinically and 300 controls in a Chinese Han population. Our results showed that minor allele “G” of rs7708392 and minor allele “C” of rs10036748 in TNIP1 gene were significantly associated with an increased the CRC risk in genotype model, dominant model and additive model after Bonferroni's multiple adjusted (P<0.0011). Moreover, the two SNPs rs7708392 and rs10036748 were in strong linkage disequilibrium. We observed that the haplotype “G-C” was more frequent among CRC patients and associated with a 1.58-fold increased CRC risk (95%CI=1.17-2.13, P=0.003). Contrarily, haplotype “C-T” was associated with a 0.63-fold reduced CRC risk (95%CI=0.47-0.86, P=0.003). Additionally, SNPs in this study except rs7708392 and rs10036748 were found a modest connection with CRC risk. In conclusion, our study firstly provides evidence for a novel association between polymorphisms of telomere length related TNIP1 gene and CRC susceptibility in Chinese Han population, and the results need a further identification in a large sample size and other populations.

Association of toll-like receptor gene polymorphisms and its interaction with HPV infection in determining the susceptibility of cervical cancer in Chinese Han population.

The aim of the study is to investigate the association of several single-nucleotide polymorphisms (SNPs) within Toll-like receptors (TLRs) gene and additional gene-gene and gene-human papillomavirus (HPV) infection interaction with cervical cancer risk. A total of 1262 participants are selected, including 420 cervical cancer patients and 842 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among five SNPs within TLR gene and HPV infection. Logistic regression was performed to calculate the ORs (95 %CI) for association of five SNPs within TLR gene and additional gene-HPV infection interaction with cervical cancer risk. Cervical cancer risk was significantly higher in carriers of the T allele of rs3775290 within TLR2 gene, the G allele of rs7873784 within TLR4 gene, and the A allele of rs352140 within TLR9 gene than those with wild genotype; adjusted ORs (95 %CI) were 1.78 (1.20-2.24), 1.65 (1.23-2.12), and 1.70 (1.16-2.31). However, we did not find any significant association of rs4986791 and rs11536889 with cervical cancer risk. GMDR analysis suggested a significant two-locus model (p = 0.0107) involving rs352140 and HPV infection. Subjects with HPV infection and rs352140-GA + AA genotype within TLR9 gene have the highest cervical cancer risk, compared to no HPV infection participants with rs352140-GG genotype, OR (95 %CI) = 3.22 (1.68-4.81). Pairwise LD analysis did not find any significant haplotype combination associated with cervical cancer risk. The minor alleles of TLR2-rs3775290, TLR4-rs7873784, and TLR9-rs352140, and interaction between rs352140 and HPV infection were all associated with increased cervical cancer risk.

Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene- gene and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han population.

AimsTo investigate the association of telomerase reverse transcriptase (TERT) gene polymorphisms and additional gene-gene and gene- environment interaction with gastric cancer (GC) risk.ResultsGC risk was significantly higher in carriers of G allele of rs2736100 than those with TT genotype (TG+ GG versus TT), adjusted OR (95%CI) =1.68 (1.26-2.17), and higher in carriers of G allele of rs2853669 than those with AA genotype (AG+ GG versus AA), adjusted OR (95%CI) = 1.72 (1.19-2.33). We also found that interaction between rs2736100 and smoking was associated with higher GC risk. Smokers with TG or GG of rs2736100 genotype have elevated GC risk, compared to never- smokers with TT of rs2736100 genotype, OR (95%CI) = 3.12 (1.82 -4.61). Pairwise linkage equilibrium (LD) analysis between SNPs was measured and the D’ value between rs2736100 and rs2736109 was more than 0.8. A haplotype containing the rs2736100- G and rs2736109- A alleles was associated with a statistically increased GC risk (OR= 2.66, 95%CI= 1.28 – 4.12, p<0.0001).Materials and MethodsA total of 1088 participants (686 males, 402 females) were selected, including 360 GC patients and 728 normal participants. Logistic regression was performed to investigate association between single nucleotide polymorphisms (SNPs) within TERT gene and GC susceptibility. Generalized multifactor dimensionality reduction (GMDR) model was used to screen gene- gene and gene- environment interaction combinations.ConclusionsWe found that G allele of rs2736100 and G allele of rs2853669 in TERT gene, interaction between rs2736100 and smoking, and haplotype containing the rs2736100- G and rs2736109- A alleles were all associated with increased GC risk.