Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population

AIM: To investigate the association between colorectal cancer(CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population.METHODS: A case-control study was conducted including 360 esophageal cancer patients and310 healthy controls. Thirty-one single-nucleotide polymorphisms(SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from HardyWeinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ 2 test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models(codominant, dominant,recessive, overdominant, and additive). ORs and95%CIs were calculated by unconditional logistic regression with adjustments for age and sex.RESULTS: The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold(95%CI:1.15-2.06; P = 0.004) and 1.28-fold(95%CI: 1.03-1.60;P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model(OR = 0.52, 95%CI:0.31-0.88; P = 0.033) and recessive model(OR =0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827C/T-T/T genotype was associated with a 0.67-fold(95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition,rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold(95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model.CONCLUSION: These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.     

Association analysis of genetic variants in microRNA networks and gastric cancer risk in a Chinese Han population

Purpose

To investigate associations between genetic variants involved in microRNA networks (microRNA biogenesis, microRNA and microRNA binding sites) and risk of gastric cancer.

Methods

We genotyped 19 SNPs of the microRNA-related genes in a case–control study of 311 gastric cancers and 425 cancer-free controls in a Chinese Han population.

Results

We found that two of the SNPs were significantly associated with gastric cancer. Inhibitory effect of minor allele T of rs2071504 SNP within the exon of POLR2A gene was significantly associated with gastric carcinogenesis (p?=?0.033, aOR?=?0.742, 95%CI?=?0.564–0.977) and the SNP rs895819 in the miR-27a gene with the minor allele C presented significantly reduced risk to gastric cancer (p?=?0.037, aOR?=?0.771, 95%CI?=?0.604–0.985). Further stratified analysis with regard to clinical pathological parameters of the patients indicated that the SNP rs2071504 was associated with lymph node metastasis (p?=?0.021, aOR?=?0.529, 95%CI?=?0.307–0.910) and TMN stage (p?=?0.021, aOR?=?0.532, 95%CI?=?0.311–0.908), respectively.

Conclusions

Our findings provided evidence that the SNP rs2071504 in the exon of POLR2A gene would not only confer a decreased risk of gastric cancer, but also influence lymph node metastasis and TMN stage of gastric cancer in the Chinese population.     

Association of genetic variants in tachykinins pathway genes with colorectal cancer risk

Purpose

This study aims to explore the associations of polymorphisms in tachykinin, precursor 1 (TAC1), tachykinin receptor 1 (TACR1), and tachykinin receptor 2 (TACR2) genes and their interactions with the risk of colorectal cancer (CRC) among Chinese population.

Methods

A population-based case-control study which included 394 cases and 393 cancer-free controls was carried out. A total of 19 tagSNPs in the three genes were chosen based on HapMap and NCBI datasets and genotyped by SNPshot assay. Multiple logistic regression models were applied to evaluate the associations of SNPs with CRC after adjustment for potential covariates. Furthermore, generalized multifactor dimensionality reduction (GMDR) method was used to test the interactive effect among three genes on CRC.

Results

Compared with those carrying rs3755457 CC/CT or rs12477554 TT/CT genotype, individuals carrying homozygous variants had higher risk of colorectal cancer (adjusted OR?=?1.80, 95?% CI?=?1.03–3.13, P?=?0.039 for rs3755457; adjusted OR?=?1.73, 95?% CI?=?1.07–2.79, P?=?0.024 for rs12477554). As for rs10198644, GG genotype was associated with a 1.72-fold (95?% CI?=?0.37–0.88) decreased risk when compared with the common CC genotype. Moreover, the GMDR analysis indicated that the best interactive model included five polymorphisms: rs2072100 (TAC1), rs10198644 (TACR1), rs2193409 (TACR1), rs3771810 (TACR1), and rs4644560 (TACR2).

Conclusions

Our study suggests that tachykinins pathway genes may participate in the development of CRC and the potential interactions among the three genes on CRC may exist, which has to be confirmed in future larger studies.     

Association between genetic variants in the IRGM gene and tuberculosis in a Korean population

Purpose

To investigate immunity-related guanosine triphosphatase family M (IRGM) genetic variants associated with susceptibility to tuberculosis (TB) in a Korean population.

Methods

We conducted a prospective case–control study including 193 patients with active TB in Severance Hospital and 230 age- and sex-matched unrelated controls registered in Yonsei Cardiovascular Genome Center. Based on associations with other chronic inflammatory conditions, we analyzed the allele and genotype frequencies of rs72553867, rs10065172, and rs12654043 among patients with TB and healthy controls.

Results

The T allele of rs10065172 was significantly associated with protection against developing TB based on allele frequency [P = 0.042; odds ratio (OR) 0.75] and genotype distribution in the codominant model (P = 0.036; OR 0.73).

Conclusions

This is the first study to identify a significant association between the IRGM single-nucleotide polymorphism (SNP) rs10065172 and susceptibility to active TB disease in an Asian population. The results suggest that IRGM genetic variants could be associated with susceptibility to active TB disease in the Korean population.     

Association between polymorphism rs6983267 and gastric cancer risk in Chinese population

AIM: To explore the association between single nucleotide polymorphisms (SNPs) at 8q24 and gastric cancer risk. METHODS: A case-control investigation including 212 gastric cancer patients and 377 healthy controls was conducted. The genotypes of SNPs (rs6983267, rs7008482 and rs10808555) were examined and established through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to evaluate the association between SNPs and gastric canc...     

Association of genetic variants of NOS1AP with type 2 diabetes in a Chinese population

Aims/hypothesis

Chromosome 1q21-q24 has been shown to be linked to type 2 diabetes. The International Type 2 Diabetes 1q Consortium showed that one of the nominal associations was located in the NOS1AP gene. Although this association was not replicated in additional samples of European descent, it remains unknown whether NOS1AP plays a role in Chinese individuals.

Methods

In stage 1 analyses, 79 single nucleotide polymorphisms (SNPs) of the NOS1AP gene were successfully genotyped in a group of Shanghai Chinese individuals, comprising 1,691 type 2 diabetes patients and 1,720 control participants. In stage 2 analyses, the SNP showing the strongest association was genotyped in additional Chinese individuals, including 1,663 type 2 diabetes patients and 1,408 control participants.

Results

In stage 1 analyses, 20 SNPs were nominally associated with type 2 diabetes (p?<?0.05), with SNP rs12742393 showing the strongest association (OR 1.24 [95% CI 1.11–1.38]; p?=?0.0002, empirical p?=?0.019). Haplotype analysis also confirmed the association between rs12742393 and type 2 diabetes. In stage 2 analyses, the difference in allele frequency distribution of rs12742393 did not reach statistical significance (p?=?0.254). However, the meta-analysis showed a significant association between rs12742393 and type 2 diabetes with an OR of 1.17 (95% CI 1.07–1.26; p?=?0.0005).

Conclusions/interpretation

Our data suggest that NOS1AP variants may not play a dominant role in susceptibility to type 2 diabetes, but a minor effect cannot be excluded.     

我国汉族人群单核甘酸多态性与前列腺癌风险的相关性研究

目的观察在欧美人群中与前列腺癌（PCa）高度相关的3个基因变异位点rs6983561、rs16901979、rs1447925与我国汉族人PEa的相关性。方法选择我国汉族PCa患者（PCa组）和正常人（对照组）各120例,采用直接测序法对其rs6983561、rs16901979、rs1447925位点单核苷酸多态性（SNP）基因进行检测,分析这3个位点SNP与PCa风险关联性。结果rs6983561C、rs16901979A等位基因与PCa风险无关联性（OR值分别为1．19、1．13,P均〉0．05）,rs1447295A等位基因与PCa风险有关联性（OR=1．63,P〈0．05）。结论我国汉族人群中rs1447295A等位基因与PCa有关联性,rs1447295A等位基因携带者PCa风险增加。     

Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population

BACKGROUND AND AIMS: Glutathione S-transferases (GSTs) are phase II detoxification enzymes. Human GSTs have been classified into cytosolic, mitochondrial, and microsomal families. Several studies reported the association of colorectal cancer (CRC) risk with the genetic polymorphisms of cytosolic GSTs. The microsomal GSTs are structurally distinct but functionally similar to cytosolic GSTs; their association with CRC has not been reported. In this report, we summarized the result of a case-control study aimed at investigating the association of MGST1 gene locus polymorphisms with CRC risk among Han Chinese. PATIENT/METHODS: Three hundred and seventy-two healthy controls and 238 sporadic CRC patients participated in this study. DNA resequencing was conducted for the 3.4 kb genomic DNA region containing the promoter, exons, exon-intron junctions, and the 5' and 3' untranslated regions. RESULTS: We detected 13 single nucleotide polymorphisms (SNPs) including four novel SNPs not reported in database/literature. The gene shows a much higher nucleotide diversity than most human genes. The linkage and recombination analysis revealed 24 common haplotypes (13% > or = freq > or = 1%) and identified extensive intragenic recombination throughout the MGST1 locus (R = 81.8). Significant CRC association (P < or = 0.005) was not detected for each individual SNP. However, SNPs 102G>A and 16416G>A reached a marginal level of statistical significance with P values of 0.016 and 0.078, respectively. A combined genotype analysis detected a statistically significant CRC association for individuals carrying 102G>A/16416G>A (GG/GG) genotype (adjusted OR, 1.682; 95% confidence interval (CI), 1.177-2.404; P = 0.004). Consistent with the results of genotype analysis, the GG haplotype (102G>A/16416G>A) with two risk alleles was associated with a significantly higher CRC risk comparing with the haplotypes with one or no risk allele (adjusted OR 1.744; 95% CI 1.309-2.322; P = 0.0001). CONCLUSION: The results suggest that MGST1 polymorphisms may contribute to CRC risk among Han Chinese.     

Combined effects of 17 common genetic variants on type 2 diabetes risk in a Han Chinese population

Aims/hypothesis  

The recent advent of genome-wide association studies has considerably accelerated the identification of type 2 diabetes loci. We aimed to investigate the combined effects of multiple genetic variants, alone or in combination with conventional risk factors, on type 2 diabetes and diabetes-related traits in Han Chinese.     

Association between CYP24A1 polymorphisms and the risk of colonic polyps and colon cancer in a Chinese population

AIM To determine the pathogenesis and potential single nucleotide polymorphisms(SNPs) as screening sites for colonic polyps,colon cancer and ulcerative colitis,and to analyze the possible association between these genetic polymorphisms and the three diseases. METHODS We evaluated genetic polymorphisms in 144 newly diagnosed colonic polyp patients,96 colon cancer patients and 44 ulcerative colitis patients. The four SNPs genotyped were rs4809957,rs6068816,rs6091822 and rs8124792. The control group consisted of 504 East Asians enrolled in the 1000 Genomes Project. Correlations between CYP24A1 SNPs and the diseases were analyzed by Fisher's exact probability test.RESULTS CYP24A1 polymorphisms rs4809957 A/G and rs6068816 C/T showed a statistically significant association with risk of the three diseases,when both the genotypes and allele frequencies were considered. With regard to rs6091822 G/T,all three diseases were related to risk allele carriers(GT + TT) vs wild-type(GG),but the associations between the allele frequencies and the diseases were not significant. The risk of colonic polyps and colon cancer was related to the allele frequencies of rs8124792 G/A,and this association remained for genotype frequencies of this SNP. CONCLUSION Four SNPs are related to the risk of colonic polyps and colon cancer. G allele in rs6091822 G/T may play an anti-cancer role only if it is homozygous. The A allele,which is a minor component of rs8124792,may be indicated in the diagnosis of colonic polyps or colon cancer rather than ulcerative colitis.     

XPG Asp1104His基因多态性与中国人口结直肠癌易感性的关系

目的已有研究报道着色性干皮病基因（XPG）Asp1104His多态性与结直肠癌易感性相关,但是结果尚不一致。本研究旨在调查XPG Asp1104His基因多态性是否与中国人口的大肠癌易感性相关。 方法应用TaqMan分析法检测878例肠癌患者和884例同期住院的非肠癌患者XPG基因的Asp1104His多态性,并分析其与肠癌遗传易感性的相关性。同时我们用荟萃分析验证这一结果。 结果我们发现XPG Asp1104His基因多态性与大肠癌遗传易感性显著相关（显性模型：His/His＋Asp/His vs Asp/Asp,调整OR=1.39,95%CI=1.14~1.69）,分层分析结果显示His/His＋Asp/His基因型与中分化肠癌易感性相关。另外,我们的荟萃分析显示相似的结果：显性模型（OR=1.35,95%CI=1.20~1.51）在亚洲人口中与肠癌发病风险明显相关。 结论我们的结果表明：XPG Asp1104His基因多态性增加亚洲人罹患肠癌的风险。