Androgen receptor (CAG)n polymorphisms and breast cancer risk in a Han Chinese population.

The androgen receptor (AR) is involved in the differentiation and growth of breast cancer. Genetic markers in the AR gene have a plausible role in modulating the risk of breast cancer. In this study, we studied the association of breast cancer and the trinucleotide repeat polymorphism (CAG)n in exon 1 of the AR gene in 202 patients with breast cancer and 183 healthy controls from our hospital (Yinchuan, China). Repeat lengths were determined by fluorescent DNA fragment analysis using the ABI GeneScan software and DNA sequencing. We detected 17 short tandem repeat alleles in exon 1 in the Han population of Ningxia Province, China. The CAG repeat number ranged from 14 to 31 and the frequency ranged from 0.339 to 24.460%. Generally, (CAG)n repeat lengths <22 were classified as short (S), and those >22 were classified as long (L). No association was found between breast cancer and the S/L (CAG) variants. However, the frequency of the (CAG)25 repeats in the breast cancer group was significantly higher than that in the control group (P = 0.033, odds ratio = 1.790, 95% confidence interval = 1.044-3.069). These findings indicate a role for AR gene (CAG)n variations in breast cancer and might be informative for future genetic or biological studies on breast cancer, although these findings need replication in other populations.

Functional polymorphisms of the glutamate receptor N-methyl D-aspartate 2A gene are associated with heroin addiction.

Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [X(2) = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.

Meta-analysis: E-cadherin immunoexpression as a potential prognosis biomarker related to gastric cancer metastasis in Asian patients.

OBJECTIVE: The prognostic potential of reduced E-cadherin expression is associated with an increased risk of gastric cancer. However, its role in gastric cancer remains poorly understood. This study was to quantitatively summarize available evidences for evaluating E-cadherin immunoexpression in Asian patients with gastric cancer as a prognostic indicator. MATERIALS AND METHODS: Searches were applied to MEDLINE, EMBASE, the Cochrane Library and Chinese Biomedicine Databases until June 2012, without language restrictions. Studies were pooled and summary risk ratio (RR) or odds ratio (OR) were calculated. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication bias were also conducted. RESULTS: Our combined results showed that reduction of E-cadherin expression in Asian patients with gastric cancer was frequently observed as compared to the counterpart normal tissue (odds ratio [OR] = 64.16, 95% confidence interval [CI] = 24.53-167.80, p < 0.001). All the analyses estimated favored a stronger link between the reduced E-cadherin expression and the poor 5 year overall survival (risk ratio [RR] = 1.50, 95% CI = 1.36-1.66, p < 0.001). When stratifying the studies by the clinical variables, the depth of invasion (OR = 2.46, 95% CI = 1.70-3.57, p < 0.001), lymph node spread (OR = 1.83, 95% CI = 1.49-2.26, p < 0.001), distant metastasis (OR = 2.04, 95% CI = 1.45-2.87, p < 0.000), and TNM stage (OR = 2.11, 95% CI = 1.58-2.83, p < 0.001) provided significant prognostic information. CONCLUSIONS: Our findings indicate that E-cadherin appears to predict the overall survival and mark metastasis in Asian patients with gastric cancer. Importantly, E-cadherin may be implemented in the routine clinical management of gastric cancer. However, further pursuit of this possibility is warranted.

Roles of functional NFKB1 and ß-TrCP insertion/deletion polymorphisms in mRNA expression and epithelial ovarian cancer susceptibility.

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological cancers. Nuclear factor-kappa B (NF-κB) is involved in carcinogenesis and in the development of EOC. The ß-transducin repeat-containing protein (ß-TrCP) is a positive regulator of the NF-κB signaling pathway. Recent studies have indicated that the -94 ins/del ATTG polymorphism in the promoter region of the NFKB1 gene, and the 9N ins/del polymorphism in the 3'-untranslated region of the ß-TrCP gene are associated with increased susceptibility to a variety of cancers. We examined a potential association between these two polymorphisms and EOC. Genotypes were determined for 187 patients with EOC and 221 healthy control subjects, using the MassARRAY system. We found a significant association between the -94 ins/del ATTG genotype distribution and EOC. The frequency of the -94 del ATTG allele was significantly lower in EOC patients compared to healthy controls. The NF-κB mRNA level in cancer tissue was significantly correlated with -94 ins/del ATTG genotypes. Compared to the ATTG1/ATTG1 phenotype, the NF-κB mRNA level was 2.089 and 1.257 times higher in the ATTG2 (insertion)/ATTG2 homozygote and the ATTG1 (deletion)/ATTG2 heterozygote, respectively. However, we found no evidence of association between the 9N ins/del polymorphism of the ß-TrCP gene and EOC in this Chinese population. Based on these results, we suggest that the NF-κB -94 ins/del ATTG polymorphism is a risk factor for EOC susceptibility.

Association study of polymorphisms in the promoter region of DRD4 with schizophrenia, depression, and heroin addiction.

This study investigated the possible association between three functional polymorphisms in the promoter region of the dopamine D4 receptor (DRD4) gene and schizophrenia, depression, and heroin addiction. Genomic DNA was isolated from the venous blood leukocytes of 322 unrelated patients with schizophrenia, 156 patients with depression, 300 patients with heroin addiction, and 300 healthy unrelated individuals. Polymorphisms in the promoter region of DRD4 (-120 bp duplication, -616C/G, and -521C/T) were genotyped using allele-specific polymerase chain reaction analysis. Genotype and allele were analyzed using SPSS 11.5 software. Results of this analysis indicated that there is a strong finding of -120 bp duplication allele frequencies with schizophrenia (p=0.008) and weak finding with -1240 L/S and for paranoid schizophrenia (p=0.022). Interestingly, there is a stronger finding with -521 C/T allele frequencies with heroin dependence (p=0.0002). These observations strongly suggest that the -120-bp duplication polymorphism of DRD4 is associated with schizophrenia and that the -521 C/T polymorphism is associated with heroin addiction.