8q24 rs4242382 polymorphism is a risk factor for prostate cancer among multi-ethnic populations: evidence from clinical detection in China and a meta-analysis.

BACKGROUND: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. MATERIALS AND METHODS: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically- confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. RESULTS: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, P=7.3?10-5), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, Padj=1.1?10-4). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ≥65 years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype (P=4.6?10-5-3.0?10-2). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, P=1.0?10-5) across Asian, Caucasian and African American populations. CONCLUSIONS: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.

rs10505474 and rs7837328 at 8q24 cumulatively confer risk of prostate cancer in Northern Han Chinese.

AIMS: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. METHODS: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. RESULTS: Among the six candidate variants, only rs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa (ORrecessive= 1.56, p=0.006); and rs7837328 (A) was associated with PCa (ORdominant= 1.38, p=0.042/ORrecessive=1.99, p=0.003). Moreover, we observed a cumulative effects between them (ptrend=2.58?10-5). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) (page=0.046, Ptumorstage =0.048). CONCLUSION: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.

Association between APOC1 polymorphism and Alzheimer's disease: a case-control study and meta-analysis.

BACKGROUND: Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer's disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations. METHODS: To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies. RESULTS: Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ(2) = 119.46, OR = 2.79, 95% CI = 2.31-3.36, P<0.01). CONCLUSIONS: The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.

Susceptibility loci associations with prostate cancer risk in northern Chinese men.

BACKGROUND: KLK3 gene products, like human prostate-specific antigen (PSA), are important biomarkers in the clinical diagnosis of prostate cancer (PCa). G protein-coupled receptor RFX6, C2orf43 and FOXP4 signaling plays important roles in the development of PCa. However, associations of these genes with PCa in northern Chinese men remain to be detailed. This study aimed to investigate their impact on occurrence and level of malignancy. METHODS: All subjects were from Beijing and Tianjin, including 266 cases with prostate cancer and 288 normal individuals as controls. We evaluated associations between clinical covariates (age at diagnosis, prostate specific antigen, Gleason score, tumor stage and aggressive) and 6 candidate PCa risk loci, genotyped by PCR- high resolution melting curve and sequencing methods. RESULTS: Case-control analysis of allelic frequency of PCa associated with PCa showed that one of the 6 candidate risk loci, rs339331 in the RFX6 gene, was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.73, 95% confidence interval (CI) =0.57-0.94, P = 0.013) in northern Chinese men. In addition, subjects with CX (CC+TC) genotypes had a decreased risk for prostrate cancer compared to those carrying the TT homozygote (OR =0.64, 95% CI = 0.45- 0.90, P = 0.008). The TT genotype of 13q22 (rs9600079, T) was associated with tumor stage (P=0.044, OR=2.34, 95% CI=0.94-5.87). Other SNPs were not significantly associated with clinical covariates in prostate cancer (P > 0.05). CONCLUSIONS. rs339331 in the RFX6 gene may be associated with prostate cancer as a susceptibility locus in northern Chinese men.

Association of six susceptibility Loci with prostate cancer in northern chinese men.

BACKGROUND/AIM: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. METHODS: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. RESULTS: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). CONCLUSION: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population.

In European populations, 7 single nucleotide polymorphisms (SNPs) on chromosome 17q, 3 SNPs on 17q12, and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study. In Japanese populations, the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment. However, whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown. Therefore, we conducted a case-control study in a northern Chinese population and tested 2 SNPs, rs4430796 and rs1859962, on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with sequencing. We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles, onset ages, Gleason scores, PSA levels, and pathologic stages. We found a significant difference in the G allele of SNP rs1859962 (P = 0.035, OR = 1.51, 95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls (P > 0.05). Neither of the SNPs was significantly associated with the onset age, Gleason score, PSA level, pathologic stage, or other clinical indicators of patients with prostate cancer (P > 0.05). Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.

[Two single nucleotide polymorphisms on chromosome 3 and the risk of prostate cancer in Chinese men].

OBJECTIVE: To investigate the correlation of the common variant single nucleotide polymorphisms (SNP) on chromosome 3 with the incidence and related risk factors of prostate cancer (PCa) in Chinese men. METHODS: Using the case-control meth- od, we included 124 PCa patients in the PCa group and 111 age- and gender-matched cancer-free healthy subjects as normal controls. We detected the distribution of allele and genotype frequencies of the SNP rs10934853 and rs2660753 with the polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with gene sequencing, analyzed the cumulative effect of the risk genotypes of these two independent variants, and determined the correlation between different genotypes of these two SNPs and clinically related risk factors in the PCa patients. RESULTS: As for the genotypes of rs10934853, there were 28 cases of AA (22.8%), 46 cases of CC (37.4%), and 49 cases of AC (39.8%) in the PCa patients, as compared with 24 (22.0%), 34 (31.2%) and 51 (46.8%) in the healthy controls. As regards the genotypes of rs2660753, there were 13 cases of AA (11.0%), 59 cases of GG (50.0%) and 46 cases of AG (39.0%) in the PCa patients, in comparison with 9 (8.8%), 47 (45.6%) and 47 (45.6%) in the controls. No significant differences were found in the distribution of the genotype and allele frequencies of rs10934853 and rs2660753 between the two groups (P = 0.520 & 0.582). Analysis on the cumulative effect of the risk genotypes of rs10934853 and rs2660753 showed a slightly higher risk of PCa (OR = 1.831 & 1.968) in the two groups with risk genotypes than in the one with wild types (P > 0.05). Different genotypes of rs10934853 and rs2660753 were not correlated with clinically related risk factors of the PCa patients (P > 0.05). CONCLUSION: SNP rs10934853 and rs2660753 on chromosome 3 are not obviously correlated with PCa in Chinese patients, and may not be a genetic risk factor of PCa.