Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets.

A genome-wide association study of gout in European populations identified 12 genetic variants strongly associated with risk of gout, but it is unknown whether these variants are also associated with gout risk in Chinese populations. A total of 145 patients with gout and 310 healthy control patients were recruited for a case-control association study. Twelve SNPs of CLNK and ZNF518B gene were genotyped, and association analysis was performed. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the association. Overall, we found four risk alleles for gout in patients: the allele "G" of rs2041215 and rs1686947 in the CLNK gene by dominant model (OR 1.66; 95 % CI 1.04-2.63; p = 0.031) (OR 2.19; 95 % CI 1.38-3.46; p = 0.001) and additive model (OR 1.39; 95 % CI 1.00-1.93; p = 0.049) (OR 1.67; 95 % CI 1.19-2.32; p = 0.003), respectively, and the allele "A" of rs10938799 and rs10016022 in ZNF518B gene by recessive model (OR 4.66; 95 % CI 1.44-15.09; p = 0.008) (OR 4.54; 95 % CI 1.23-16.76; p = 0.020). Further haplotype analysis showed that the TCATTCTGA haplotype of CLNK was more frequent among patients with gout (adjusted OR 0.48; 95 % CI 0.24-0.95; p = 0.036). Additionally, polymorphisms of rs2041215, rs10938799, and rs17467273 were also correlated with clinical pathological parameters. This study provides evidence for gout susceptibility genes, CLNK and ZNF518B, in a Chinese population, which may have potential as diagnostic and prognostic marker for gout patients.

Genetic variation in the TP63 gene is associated with lung cancer risk in the Han population.

Lung cancer is one of the most common malignant tumors that seriously threaten human health. Current evidence suggests that heredity contributes to the progression of lung cancer. To investigate and validate potential genetic associations with the risk of lung cancer, we conducted a case-control study including 309 cases and 310 controls from Xi'an City, which is located in northwest China, and genotyped six SNPs in five genes, which are related to metabolic process. Overall, our results show that the SNP rs10937405 was associated with a decreased occurrence of lung cancer (OR = 0.72; 95% CI = 0.56-0.92; p = 0.009). In the genetic models analysis, we found that genotype "CT" of rs10937405 in TP63 was associated with a decreased lung cancer risk (OR = 0.71; 95% CI, 0.51-0.99; p = 0.031); the genotype "TT" of rs10937405 showed a decreased lung cancer risk in the co-dominant model (OR = 0.53; 95% CI, 0.30-0.95; p = 0.031). The genotype "CT-TT" of rs10937405 also showed a decreased lung cancer risk in the dominant model (OR = 0.67; 95% CI, 0.49-0.92; p = 0.014) and the log-additive model (OR = 0.72; 95% CI, 0.56-0.92; p = 0.0085). The genotype "CC-CT" of rs10937405 confers a higher risk of lung cancer for males than females. Our results, combined with those from previous studies, suggest that genetic variation in TP63 may influence lung cancer susceptibility in the Han population.

Genetic association of CHEK2, GSTP1, and ERCC1 with glioblastoma in the Han Chinese population.

Glioblastoma (GBM), a deadly brain tumor, is the most malignant glioma. It mainly occurs in adults and occurs significantly more in males than in females. We genotyped 19 tag single nucleotide polymorphisms (tSNPs) from 13 genes in a case-control study of the Han Chinese population to identify genetic factors contributing to the risk of GBM. These tSNPs were genotyped by Sequenom MassARRAY RS1000. Statistical analysis was performed using χ(2) test and SNPStats, a website software. Using χ(2) test, we found that the distribution of two tSNPs (rs2267130 in checkpoint kinase 2 (CHEK2), p = 0.040; rs1695 in GSTP1, p = 0.023) allelic frequencies had significant difference between cases and controls. When we analyzed all of the tSNPs using the SNPStats software, we found that rs1695 in GSTP1 decreased the risk of GBM in log-additive model (OR = 0.56, 95% CI, 0.34-0.94, p = 0.022). Besides, we found that there is an interaction between rs3212986 in excision repair cross-complementing group 1 (ERCC1) and gender under codominant and recessive models. The gene polymorphisms in CHEK2, GSTP1, and ERCC1 may be involved in GBM in the Han Chinese population. Since our sample size is small, further investigation needs to be performed.

RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population.

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case-control study from Xi'an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population.

Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.

[Genetic polymorphisms of 10 X chromosome STR loci in a Chinese Tibetan population].

OBJECTIVE: To investigate the alleles and genotypes frequency of 10 short tandem repeat (STR) loci on the X chromosome(DXS7423, DXS8378, DXS6799, DXS7424, DXS7130, DXS7132, DXS6789, DXS101, DXS6804, DXS7133) of Tibetan individuals living in Xizang Autonomous Region, Southwest China. METHODS: The 10 X-chromosomal STR loci were analyzed with PCR, followed by polyacylamide gel electrophoresis and silver staining. RESULTS: Among unrelated Tibetan individuals, the numbers of alleles in the 10 X-STR loci(DXS7423, DXS8378, DXS6799, DXS7424, DXS7130, DXS7132, DXS6789, DXS101, DXS6804, DXS7133) were 5, 5, 5, 9, 7, 7, 11, 9, 5 and 4, respectively. The genotype frequencies in females were in accordance with Hardy-Weinberg equilibrium. CONCLUSION: The 10 X-chromosomal STRs loci are appropriate for individual identification, for paternity testing involving a female child, and for studies on related disease.

[The genetic polymorphism of 9 short tandem repeat loci in Yi ethnic group of Yunnan in China].

OBJECTIVE: To study the short teadem repeat(STR) genetics structure of a Chinese Yunnan Yi racial group. METHODS: Genetic distributions for nine STR loci were determined based on STR gene scan marked by fluorescence. RESULTS: Sixty-nine alleles and 164 kinds of genotypes were detected and identified from 84 unrelated Yi racial individuals. The corresponding gene and genotype frequencies were in 0.0060-0.5060 or 0.0119-0.4167 respectively. The expected and observed genotype frequencies of nine STR loci were in accordance with the Hardy-Weinberg equilibrium(P>0.05). The statistical analyses of nine STR loci showed that PIC was distributed in 0.5804-0.8777, H was in 0.6507-0.8002, DP was in 0.7976-0.9558, EPP was in 0.5207-0.8386, except TPOX and THO1 loci. CONCLUSION: Above research data enrich the Chinese genetic database, and play an important role in Chinese genetic study and in forensic application.

[Genetic relationships between Ewenki minority in Inner Mongolia and other 14 groups].

OBJECTIVE: To study the STR genetic structure of an Ewenki Ethnic minority Group of Inner Mongolia, and analyze the genetic relationship among Ewenki and other 14 groups. METHODS: Genetic distribution for 9 STR loci (D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, and D7S820) were determined based on gene scan marked by fluorescence. Principle component analysis was performed using SPSS. RESULTS: Sixty-four alleles and 158 genotypes were observed in 90 unrelated Ewenki individuals. The corresponding gene frequency and genotype frequency was 0.0056 to 0.4722 and 0.0111 to 0.3, respectively. The expected and observed genotype frequency of the 9 STR loci were in accordance with the Hardy-Weinberg equilibrium (P>0.05). The principle component analysis showed that Ewenki clustered with groups of Mongolian and Tujue language branch. CONCLUSION: Nine of the STR genetic structure of an Ewenki Ethnic minority Group of Inner Mongolia were obtained. Those ethnic groups in subfamilies of Altaic language family clustered as their geographical location and those with close genetic relationships use similar language.

[Genetic polymorphisms and application of 9 STR loci of 5 ethnic groups in Gansu and Qinghai].

OBJECTIVE: To examine the genetic polymorphism of 9 STR loci in 5 ethnic groups (including Tu, Sala, Dongxiang, Baoan and Yugu) in Gansu and Qinghai, and to evaluate its application. METHODS: Nine STR loci (D3S1358, FGA, TH01, D7S820, VWA, CSF1PO, D5S818, D13S317 and TPOX) were selected as genetic markers. With STR compound amplification and genescan methods, in which STR loci were marked by fluorescence, the genotype of 5 ethnic groups were examined in 606 unrelated individuals by ABI 377 sequencer. These parameters, such as polymorphism information content (PIC), heterozygosity (H), discrimination power (DP) and probability of paternity exclusion (PPE) were calculated. RESULTS: The genotype frequencies of the 9 STR loci were in accordance with Hardy-Weinberg equilibrium. PIC was within 0.6054 - 0.8735, H was within 0.6158 - 0.8736, DP was within 0.7964 - 0.9691, and PPE was within 0.4610 - 0.8838. Cluster analysis based on allele frequencies in genesis showed Tu, Sala, Dongxiang and Baoan ethnic groups were very close, but Yugu was a little bit far. There were obvious gene exchanges among the populations in north and south of China. CONCLUSION: All the 9 STR loci are highly polymorphic in the 5 ethnic groups, which can be useful genetic markers in forensic medicine and population genetics.

The population genetics of pharmacogenomics VIP variants in the Sherpa population.

Polymorphic distributions of pharmacogenes among some ethnicities are under-represented in current pharmacogenetic research. Particularly, there is a paucity of pharmacogenetic information in the Sherpa population in Tibet. We used the Sequenom MassARRAY single nucleotide polymorphism (SNP) genotyping technology to detect 86 very important pharmacogene (VIP) variants in Sherpas and compared the genotypic frequencies of these variants with HapMap populations. Overall, 59 of the 60 previously reported variants in the HapMap populations were found in our study. We found minimal differences between populations of Sherpas and Chinese Han in Beijing (CHB), Chinese in Metropolitan Denver, Colorado (CHD), Japanese in Tokyo, Japan (JPT), and Mexicans in Los Angeles, California (MEX) after a strict Bonferroni correction. Only 8, 4, 5, 4 VIP genotypes, respectively, were different in these groups. Additionally, pairwise FST values and clustering analyses showed that the VIP variants in the Sherpa population exhibited a close genetic affinity with the CHB and JPT populations, but they were most similar to the CHD population. Our results contribute to a better understanding of the molecular basis underlying ethnic differences in drug response, which may potentially benefit the development of personalized medicine for the Sherpa population.

Polymorphism in the IL4R gene and clinical features are associated with glioma prognosis: Analyses of case-cohort studies.

Inflammatory gene polymorphisms may be associated with glioma risk. The purpose of this study was to analyze effects of certain inflammatory gene and some clinical factors on patient survival.The clinical information of 269 glioma patients conceived operation from September 2010 to May 2014 to decide the 1-, 3-year survival rates according to follow-up results and analyze age, gender, the WHO classification, extent of surgical resection, radiotherapy and chemotherapy factors effects on prognosis. Survival distributions were estimated by using the Kaplan-Meier method and difference in the survival was tested using the log-rank test. To estimate the association between the IL4, IL13, IL10, IL4R SNPs, and PFS and OS in glioma, the HR and 95% CI were calculated by univariate Cox proportional hazards model. Multivariate Cox model were performed to compute adjusted HR and 95% CI. All data was analyzed with SPSS17.0 package. Extent of surgical resection, chemotherapy, and age are an important factor in glioma overall survival and progression-free survival overall. Extent of surgery and chemotherapy are important factors in astrocytoma overall survival. Univariate analysis showed that IL4R rs1801275 was significantly associated with overall survival of glioma and astrocytoma patients (P < 0.05). Multivariate Cox regression analysis showed that IL4R rs1801275 GG genotype could increase the death risk of glioma and astrocytoma patients (Glioma: hazard ratio [HR]: 4.897, 95% confidence limits [95% CI]: 1.962-12.222, P = 0.001; Astrocytoma: HR: 15.944, 95% CI: 4.019-63.253, P < 0.05).Our research results showed that extent of surgical resection, age, and chemotherapy affect the prognosis of glioma. The IL4R gene may affect the survival of glioma patients.

Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study.

Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61-0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55-0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff-Bloom-Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.

PD-1 rs2227982 Polymorphism Is Associated With the Decreased Risk of Breast Cancer in Northwest Chinese Women: A Hospital-Based Observational Study.

Programmed death-1 (PD-1) is crucial in cancer and is well characterized as a negative T-cell regulator that functions by delivering inhibitory signals. We aimed to evaluate the relationship between PD-1 polymorphisms (rs10204525, rs2227982, and rs7421861) and breast cancer risk.We selected 560 breast cancer patients and 583 age-, sex-, and ethnicity-matched healthy controls from Northwest China. The PD-1 polymorphisms were genotyped by using Sequenom MassARRAY. Associations were estimated with odds ratios (ORs) and 95% confidence intervals (95% CIs).For the rs10204525 and rs7421861 polymorphisms, no differences in breast cancer risk were found in any of the genetic models. For the rs2227982 polymorphism, the variant genotypes were significantly associated with decreased breast cancer risk (CT vs CC: OR = 0.68, 95% CI = 0.52-0.91; CT + TT vs CC: OR = 0.69, 95% CI = 0.53-0.90). In analyses stratified by age, the decreased risk was observed among the younger subjects (OR = 0.68, 95% CI = 0.47-0.97). We found that the decreased risk observed for the variant genotypes of rs2227982 was associated with the Her-2 status (CT vs CC: OR = 0.55, 95% CI = 0.37-0.84; CT + TT vs CC: OR = 0.56, 95% CI = 0.38-0.82). The haplotype analysis showed that the Ars10204525 Trs2227982 Crs7421861 haplotype was associated with a significantly decreased risk of breast cancer (OR = 0.50, 95% CI = 0.34-0.75).Our findings support an association between the PD-1 rs2227982 polymorphism and decreased breast cancer risk, especially in Her-2 positive breast cancer patients in the Chinese population.

Association Between Single Nucleotide Polymorphisms in DNA Polymerase Kappa Gene and Breast Cancer Risk in Chinese Han Population: A STROBE-Compliant Observational Study.

DNA polymerases are responsible for ensuring stability of the genome and avoiding genotoxicity caused by a variety of factors during DNA replication. Consequently, these proteins have been associated with an increased cancer risk. DNA polymerase kappa (POLK) is a specialized DNA polymerase involved in translesion DNA synthesis (TLS) that allows DNA synthesis over the damaged DNA. Recently, some studies investigated relationships between POLK polymorphisms and cancer risk, but the role of POLK genetic variants in breast cancer (BC) remains to be defined. In this study, we aimed to evaluate the effects of POLK polymorphisms on BC risk.We used the Sequenom MassARRAY method to genotype 3 single nucleotide polymorphisms (SNPs) in POLK (rs3213801, rs10077427, and rs5744533), in order to determine the genotypes of 560 BC patients and 583 controls. The association of genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CIs) from logistic regression analyses.We found a statistically significant difference between patient and control groups in the POLK rs10077427 genotypic groups, excluding the recessive model. A positive correlation was also found between positive progesterone receptor (PR) status, higher Ki67 index, and rs10077427 polymorphism. For rs5744533 polymorphism, the codominant, dominant, and allele models frequencies were significantly higher in BC patients compared to healthy controls. Furthermore, our results indicated that rs5744533 SNP has a protective role in the postmenopausal women. However, we failed to find any associations between rs3213801 polymorphism and susceptibility to BC.Our results indicate that POLK polymorphisms may influence the risk of developing BC, and, because of this, may serve as a prognostic biomarker among Chinese women.

Distinct role of the Fas rs1800682 and FasL rs763110 polymorphisms in determining the risk of breast cancer among Han Chinese females.

BACKGROUND: In recent years, studies have demonstrated that polymorphisms in the promoters of Fas and FasL are significantly associated with breast cancer risk. However, the results of these studies were inconsistent. This case-control study was performed to explore the associations between Fas rs1800682 and FasL rs763110 polymorphisms and breast cancer. MATERIALS AND METHODS: A hospital-based case-control study of 560 Han Chinese females with breast cancer (583 controls) was conducted. The MassARRAY system was used to search for a possible association between the disease risk and the two single nucleotide polymorphisms, Fas rs1800682 and FasL rs763110. Statistical analyses were performed using SNPStats software to conduct Pearson's chi-square tests in five different genetic models. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjustment to age and body mass index. PHASE v2.1 software was used to reconstruct all common haplotypes. RESULTS: A statistically significant association was found between Fas rs1800682 and increased breast cancer risk (AG vs AA: OR =1.37, 95% CI =1.06-1.78; AA+AG vs GG: OR =1.32, 95% CI =1.04-1.66), and also it was found that the FasL rs763110 polymorphism may decrease the risk. Stratified analyses demonstrated that the rs763110 polymorphism was associated with lower breast cancer risk among postmenopausal females (heterozygote model: OR =0.69, 95% CI =0.49-0.97; dominant model: OR =0.70, 95% CI =0.51-0.96). The T allele of rs763110 was also associated with a decreased risk of lymph node metastasis (allele model: OR =0.75, 95% CI =0.57-0.97) and an increased risk of the breast cancer being human epidermal growth factor receptor 2 positive (allele model: OR =1.37, 95% CI =1.03-1.18). Moreover, haplotype analysis showed that Ars1800682Trs763110 was associated to a statistically significant degree with lower risk of breast cancer (OR =0.70, 95% CI =0.53-0.91). CONCLUSION: These data suggest that the presence of Fas rs1800683 is an important risk factor for breast cancer, whereas FasL rs763110 may exert a protective effect against the onset of breast cancer.

Genetic polymorphisms of 15 STR loci in Han population from Shaanxi (NW China).

The genetic polymorphisms of 15 STR loci, namely D3S1358, D5S818, D7S820, D13S317, vWA, FGA, TH01, TPOX, CSF1PO, D16S539, D8S1179, D21S11, D18S51, D19S433 and D2S1338, were studied in 203 unrelated Han population from Shaanxi province using AmpF/STR Identifiler kit.

CHRNA5 polymorphisms and risk of lung cancer in Chinese Han smokers.

Lung cancer is the most frequent cancer among men in many countries. It is the result of interactions between genetic and environmental factors, among which tobacco smoking is a key environmental factor. CHRNA5, Cholinergic Receptor, Neuronal Nicotinic, Alpha Polypeptide-5, was previously reported to be associated with lung cancer risk. To identify the genetic susceptibility and tobacco smoking that influence lung cancer risk in Han population, we performed a case-control study in 228 patients and 301 controls. These data were compared using the χ(2)-test, genetic model analysis, and haplotype analysis. rs495956, rs680244, rs601079, rs555018, 588765 and rs11637635 showed an increased risk of lung cancer in both allelic model and genetic mode analysis. The genotype G/A-A/A of rs11637635 was most strongly associated with a 2.17-fold increased risk of lung cancer in dominant model (p = 0.018). One SNP, rs684513, was associated with a 0.645-fold decreased risk (p = 0.033) in allelic model analysis. By haplotype association analysis, haplotype sequences CTTATCAAAGA and GA of CHRNA5 were found to be associated with a 2.03-fold and 1.91-fold increased lung cancer risk (p < 0.05). Our results, combined with those from previous studies, suggest that genetic variation in CHRNA5 may influence susceptibility to lung cancer among Han smokers.

Meta-analysis of the association between the rs8034191 polymorphism in AGPHD1 and lung cancer risk.

BACKGROUND: Possible associations between the single nucleotide polymorphism (SNP) rs8034191 in the aminoglycosidephosphotransferase domain containing 1 (AGPHD1) gene and lung cancer risk have been studied by many researchers but the results have been contradictory. MATERIALS AND METHODS: A computerized search for publications on rs8034191 and lung cancer risk was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between rs8034191 and lung cancer risk with 13 selected case-control studies. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were also performed. RESULTS: A significant association between rs8034191 and lung cancer susceptibility was found using the dominant genetic model (OR=1.344, 95% CI: 1.285-1.406), the additive genetic model (OR=1.613, 95% CI: 1.503-1.730), and the recessive genetic model (OR=1.408, 95% CI: 1.319-1.503). Moreover, an increased lung cancer risk was found with all genetic models after stratification of ethnicity. CONCLUSIONS: The association between rs8034191 and lung cancer risk was significant using multiple genetic models, suggesting that rs8034191 is a risk factor for lung cancer. Further functional studies of this polymorphism and lung cancer risk are warranted.

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 and 310 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 Hardy-Weinberg 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 and 95%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 rs4939827 C/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.

Multiple genetic variants are associated with colorectal cancer risk in the Han Chinese population.

Colorectal cancer (CRC) is a major health burden worldwide and is the second-leading cause of cancer-related death in Europe. CRC is a complex disease resulting from a series of genetic and epigenetic changes that lead to a stepwise progression from normal mucosa to dysplasia and finally to carcinoma. In this study, we present genetic association results between 25 tag single-nucleotide polymorphisms and CRC in a case-control study (203 cases, 296 controls) of a Han Chinese population. We found that rs1143634 in the interleukin-1ß (IL1B) gene and rs1800871 in the interleukin-10 (IL10) gene were associated with increased risk for CRC in the Han Chinese. Further haplotype analysis revealed that the 'GAC' in the SMAD7 (mothers against decapentaplegic homolog 7) gene was found to increase CRC risk (odds ratio=1.48; 95% confidence interval, 1.09-2.01; P=0.012). Our results, combined with previous studies, suggest that IL10, PSCA, IL1B, and SMAD7 are significantly correlated with CRC susceptibility in the Han Chinese population.