Association of VEGF genetic polymorphisms with prostate carcinoma risk and clinical outcome

OBJECTIVES: Vascular endothelial growth factor (VEGF) is a potent stimulus of angiogenesis that has an important role in many human malignancies including prostate carcinoma (PCa). We evaluated the role of the functional VEGF polymorphisms as genetic markers for PCa susceptibility and prognosis. METHODS: The study included 101 patients with PCa and [corrected] 100 age-matched healthy men. The VEGF genotypes -1154G>A were identified by allele-specific polymerase chain reaction (AS-PCR) and the genotypes -634G>C and 936C>T were identified by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). RESULTS: A negative association was found between VEGF -1154AA genotype and PCa risk (OR=0.27; P=0.009). Furthermore, the presence of the VEGF -1154A allele appeared to be associated with a decreased [corrected] risk of higher tumor grade (OR=0.37; P=0.01). A significant increased risk of prostate cancer was associated with the VEGF -634 (GC+CC) combined genotype (OR=1.95; P=0.02). The VEGF -634C allele was associated with the aggressive phenotype of prostate cancer as defined by the high histological grade (OR=3.48; P=0.007). The VEGF -1154A/-634G haplotype was negatively associated with PCa risk (OR=0.48; P=0.005) and high tumor grade compared to low grade (OR=0.37; P=0.02). CONCLUSIONS: Genetic variations in the VEGF may predict not only PCa risk but also tumor aggressiveness.     

Association of caspases with an increased prostate cancer risk in north Indian population

Dysregulation of apoptosis plays a crucial role in carcinogenesis. Thus, genetic alterations within caspase genes would be expected to provoke a deficient apoptotic signaling thereby facilitating the development of prostate cancer (PCa). In the present study we investigated whether three different polymorphisms in the caspase-5 and -3 genes are differentially expressed in PCa. In a hospital-based case control study in northern India, we genotyped 192 PCa patients and 225 unrelated healthy controls for caspase-5 (G>C) (T>C) and caspase-3 (G>A) polymorphisms using amplification refractory mutation system and polymerase chain restriction fragment length polymorphism methods. Data were statistically analyzed and variant genotype GG of caspase-3 demonstrated increased risk for PCa (odds ratio [OR]=2.72, p=0.005). Similarly variant allele carrier (AG+GG) (OR=1.53, p=0.034) and G allele (OR=1.54, p=0.005) were also statistically associated with PCa risk. High risk for PCa was also observed with respect to caspase-5 (CC) diplotypes (OR=21.67, p=0.012, Pc=0.048). We observed significantly enhanced risk for PCa due to interaction between caspase-3 and -5 gene polymorphisms. In association of genotypes with clinical characteristics, heterozygous TC genotype of caspase-5 (T>C) conferred risk with high Gleason grade tumor (OR=2.35, p=0.042). In case-only analysis, interaction of environmental risk factors and genotypes did not further modulate the risk for PCa. Our observations suggested positive association of caspase-3 and diplotype analysis of caspase-5 to be associated with PCa risk. Interaction of caspase-3 and -5 genotypes also modulated the PCa risk.     

Association of hsp70-2 and hsp-hom gene polymorphisms with risk of acute high-altitude illness in a Chinese population

High-altitude illness (HAI) is a potentially fatal condition involving genetic and environmental components. Accumulated experimental evidence suggests that heat shock proteins (Hsps), especially HSP70, can protect cells and organs against different types of damage. We investigated whether genetic variation in constitutive and inducible hsp70 genes could be associated with risk of HAI. The association between polymorphisms of the HSP70 family genes and risk of HAI was determined in 56 patients with HAI and in 100 matched controls by genotyping for the polymorphisms +190 G/C, +1267 A/G, 2437 G/C in the hsp70-1, hsp70-2, and hsp70-hom genes by using polymerase chain reaction-restriction fragment length polymorphism. The data showed that there was no statistically significant difference in the genotype and allele distributions of hsp70-1, in hsp70-2 allele and hsp70-2 A/A and A/B genotypes, and in allele distribution of hsp70-hom among patients with HAI and controls (chi2 test, P > 0.05). However, there was a significantly higher frequency of hsp70-2 B/B and hsp70-hom A/A and B/B genotypes and a significantly lower frequency of the hsp70-hom A/B genotype in the HAI patients compared with the controls (P < 0.05 for all). The risk associated with the hsp70-2 B/B and hsp70-hom A/A, A/B, and B/B genotypes were 4.017 (95% CI = 1.496-10.781; P = 0.004), 2.434 (95% CI = 1.184-5.003; P = 0.012), 0.299 (95% CI = 0.148-0.602, P = 0.001), and 5.880 (95% CI =1.145-30.196, P = 0.026), respectively. Our results suggest that individuals with hsp70-2 B/B and hsp70-hom A/B and B/B genotypes may be more susceptible to HAI, whereas those with hsp70-hom A/B genotype may be tolerant to HAI. Further studies in individuals of different age and sex are warranted to elucidate the underlying mechanisms of this association and the possible functions of different genotypes of hsp70-2 and hsp70-hom under hypoxic stress.     

Association between VHL single nucleotide polymorphism (rs779805) and the susceptibility to prostate cancer in Chinese

The Von Hippel-Lindau (VHL) tumor suppressor gene is a crucial regulator of the hypoxia response pathway and plays an important role in tumorigenesis, particularly in tumor growth and vascularization. We hypothesize that polymorphisms in the functional region of VHL may influence susceptibility to prostate cancer (PCa). We genotyped a potentially functional polymorphism (rs779805) in 5' UTR region of VHL in a case-control study of 665 PCa patients and 715 cancer-free controls in a Chinese population using the Taqman assay. The genetic associations between the incidence and progression of PCa were assessed by logistic regression. We observed that the rs779805 A>G polymorphism was significantly associated with risk for PCa. Compared with the AA genotype, the AG and AG/GG genotypes were associated with decreased risk of PCa (adjusted odds ratio [OR]=0.79, 95% confidence interval [CI]=0.62-0.99, and adjusted OR=0.76, 95% CI=0.61-0.95, respectively). Further, this decreased risk was more pronounced in the subgroups of nonsmokers (OR=0.73, 95% CI=0.54-0.98), nondrinkers (OR=0.70, 95% CI=0.54-0.91) and patients without family history of cancer (OR=0.72, 95% CI=0.57-0.92). In addition, the decreased risk associated with rs779805 variant genotypes (AG/GG) was more pronounced among the prostate specific antigen (PSA)>20 ng/mL subgroup (OR=0.68, 95% CI=0.49-0.95). Our findings suggest that the rs779805 A>G polymorphism in VHL may confer susceptibility to PCa in the Chinese population.     

Role of cyclooxygenase-2 functional gene polymorphisms in Helicobacter pylori induced gastritis and gastric atrophy

In India, the role of host genetic factors is poorly studied for Helicobacter pylori associated diseases. Therefore, we evaluated the association of functionally relevant COX-2 gene polymorphisms (-765 G>C and +8473 T>C) in gastritis and precancerous lesions susceptibility. After upper GI endoscopy, 130 rapid urease test positive patients with non-ulcer dyspepsia, also showed positivity for H. pylori using modified Geimsa staining and anti-CagA IgG serology were included. All patients and 260 asymptomatic controls were genotyped for COX-2 variations using PCR-RFLP. COX-2 -765 (GC+CC) genotypes, -765 C allele, +8473 CC genotype, +8473 (TC+CC) genotypes, +8473 C allele, and variant haplotypes imparted high risk for gastritis (P = 0.036, OR = 1.82; P = 0.007, 1.92; P = 0.025, OR = 2.13; P = 0.017, OR = 1.80; P = 0.017, OR = 1.45; P = 0.010, OR = 2.40; P = 0.023, OR = 1.50 and P = 0.012, OR = 2.20 folds, respectively). In contrast, COX-2 -765 C allele carriers had low risk for lymphocyte (P = 0.020, OR = 0.35), plasma cell infiltrations (P = 0.016, OR = 0.33), and gastric atrophy (GA) development (P = 0.019, OR = 0.35). In conclusion, COX-2 variant allele/genotype/haplotype carriers may be at high risk for gastritis. However, COX-2 -765 C allele carriers may be at low risk for GA development.     

Long non-coding RNA POLR2E gene polymorphisms increased the risk of prostate cancer in a sample of the Iranian population

The current study aimed to examine the impact of POLR2E rs1046040 and rs3787016 polymorphisms on prostate cancer (PCa) risk in a sample of southeast Iranian population. The present case-control study was performed on 178 patients with PCa and 180 benign prostatic hyperplasia (BPH). Genotyping of the variants was done by mismatch PCR-RFLP. The findings showed that the rs3787016 C?>?T variant significantly increased the risk of PCa in codominant (OR?=?1.84, 95% CI?=?1.12-3.03, P?=?0.018, CT vs CC), dominant (OR?=?1.88, 95% CI?=?1.63-3.05, P?=?0.011, CT?+?TT vas CC) and allele (OR?=?1.77, 95% CI?=?1.52-2.72, P?=?0.010, T vs C) inheritance model. Regarding rs1046040 C?>?T polymorphism, the findings revealed that the CT genotype significantly increased the risk of PCa compared to the CC genotype (OR?=?1.60, 95% CI?=?1.03-2.49, P?=?0.043). Furthermore, rs3787016 CT/rs1046040?CC as well as rs3787016 CT/rs1046040 CT increased the risk of PCa compared to the CC/CC genotype (p?=?0.029 and p?=?0.014, respectively). Haplotype analysis proposed that rs3787016 T/rs1046040 C significantly increased the risk of PCa compared to C/C (p?=?0.037). No significant association was observed between POLR2E variants and clinicopathological characteristics of PCa patients. In conclusion, the findings propose that POLR2E variants may be a risk factor for susceptibility to PCa in a sample of Iranian population.     

Prostate cancer with variants in CYP17 and UGT2B17 genes: a meta-analysis

Both CYP17 and UGT2B17 are suggested to be potential risk factors of prostate cancer (PCa). To date, many studies have evaluated the relationship between CYP17 T-34C and UGT2B17 Del polymorphisms and Prostate cancer with conflicting results. Here, we performed comprehensive meta-analyses of over 25 studies, including results from about 17,000 subjects on the association of CYP17 T-34C and UGT2B17 Del polymorphisms with Prostate cancer. Overall, no significant associations between CYP17 T-34C polymorphism and Prostate cancer risk were found for T versus C (P=0.63), TT versus CC (P=0.52), TT+TC versus CC (P=0.40) or TT versus TC+CC (P=0.98), though there was a marginally significant association with the UGT2B17 Del polymorphism under Del/Del versus Ins/Ins +Ins/Del (P=0.05). In an analysis of various subgroups, there were no substantially significant associations with the CYP17 T-34C polymorphism; while there was a significant association for the UGT2B17 Del/Del genotype in a subgroup of men-based controls (P < 0.0001). The current meta-analysis results suggest that the CYP17 T-34C polymorphism may not be associated with Prostate cancer, while the UGT2B17 Del polymorphism may significantly contribute to prostate cancer susceptibility in men. These findings also support the idea that CYP17 has no significant effects on androgen levels, while UGT2B17 does.     

apelin基因rs2235306位点多态性与哮喘的相关性研究

目的:探讨apelin基因rs2235306位点多态性与哮喘的相关性。方法:以外周血全血DNA为模板,应用四引物扩增受阻突变体系PCR(Tetra-primer ARMS PCR,T-ARMS-PCR)方法对158例哮喘患者(AS)和79例健康个体(NC)apelin基因rs2235306位点基因型进行分析,同时进行肺功能检查(FEV1、FVC、FEV1/FVC)。结果:AS组和NC组apelin基因rs2235306位点等位基因T和C频率分布具有统计学意义(X2=6.906,P=0.009,OR=1.688,95%CI=1.140-2.497),AS组C等位基因频率显著高于健康对照组;AS组和NC组基因型分布具有统计学意义(X2=14.243,P=0.000,OR=3.894,95%CI=1.861-8.149),其中CC基因型患哮喘的风险较高,为TT+TC基因型的3.894倍。AS轻度组和AS中重度组基因型CC和TT+TC频率及等位基因T和C频率比较均无统计学意义。结论:apelin基因rs2235306位点多态性和哮喘的发病具有一定的相关性,C等位基因可能是哮喘的遗传易感基因,CC基因型携带者哮喘的患病风险可能增加,但与哮喘的严重程度无明显相关性。     

RNASEL 1623A>C variant is associated with the risk of prostate cancer in African descendants

Association between ribonuclease L (RNASEL) gene 1623A>C polymorphism and prostate cancer (PCa) susceptibility has been assessed in large quantities of studies but with controversial conclusions. We undertook a pooled analysis containing 7397 PCa cases and 6088 control subjects to assess the correlation between RNASEL 1623A>C polymorphism and PCa risk. Moreover, we used enzyme-linked immunosorbent assay to test the serum RNASEL expression among patients enrolled in our centers and in-silico tools were also utilized. The overall results of our analysis indicated a positive relationship between 1623A>C variant and PCa risk (allelic contrast, odds ratio [OR] = 1.07; 95% confidence interval [CI] = 1.02-1.12; P_{heterogeneity} = 0.575; CC vs AA, OR = 1.14; 95% CI = 1.03-1.26; P_{heterogeneity} = 0.217; CC + CA vs AA, OR = 1.10; 95% CI = 1.01-1.19; P_{heterogeneity} = 0.303; and CC vs CA + AA, OR = 1.08; 95% CI = 1.00-1.17; P_{heterogeneity} = 0.298). In ethnicity subgroup analysis, similar results were especially indicated in African descendants. In addition, serum RNASEL levels in PCa cases with CC + CA genotypes were higher than those with AA genotypes. Our present study showed evidence that RNASEL 1623A>C polymorphism is related to PCa risk, especially in African descendants.     

The GADD45A (1506T>C) Polymorphism Is Associated with Ovarian Cancer Susceptibility and Prognosis

GADD45A (growth arrest and DNA damage 45 A) is the first stress-inducible gene identified to be a target of p53. However, no studies to date have assessed variants of the GADD45 gene and their potential relationship to tumor susceptibility. We investigated the association of the GADD45A (1506T>C) polymorphism with ovarian cancer development in 258 ovarian cancer patients and 332 age-matched healthy women as controls using sequence analysis. We found a statistically significant difference in the GADD45A (1506T>C) genotype distributions between the case and control groups (TT vs. TC vs. CC, P = 0.0021) and found that variant 1506T>C was significantly associated with an increased risk of ovarian cancer (P<0.001, OR = 1.71, 95% CI [1.28–2.29]). We observed a statistically significant effect between tumor histology (P = 0.032) and CA125 status (P = 0.021). Carrying the C allele (TC+CC) was associated with an increased risk of positive CA125 (OR = 3.20, 95% CI [1.15–8.71). Carrying the T allele (TT+TC) showed a significant correlation with both higher GADD45A mRNA expression and longer ovarian cancer RFS (relapse-free survival) and OS (overall survival). We are the first group to demonstrate that the GADD45A (1506T>C) polymorphism is associated with ovarian cancer susceptibility and prognosis. These data suggest that GADD45A (1506T>C) is a new tumor susceptibility gene and could be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis.     

IL-17Frs763780多态性和肿瘤易感性关联的Meta分析

目的评估IL-17Frs763780多态性与癌易感性的关联。方法通过检索Pubmed、Embase、OV-ID、CBM、WanfangData和CNKI,筛选出发表至2013年10月与IL-17基因多态性和癌易感性有关的病例对照研究。采用比值比（ORs）和95％可信区间（95％CIs）评价关联强度。结果最终纳入5篇病例对照研究,包括1407例肿瘤患者和2164例健康对照。然而,分析后发现IL-17Frs763780多态性和癌无统计学意义的关联（TT＋TC vs CC：OR=0．85,95％CI=0．46～1．57,P=0．60;TTVSTC＋CC：OR=1．00,95％CI=0．76-1．33,P=0．99;TC vs CC：OR=0．83,95％CI=0．44—1．55,P=0．55;TT vs CC：OR=0．85,95％CI=0．46-1．59,P=0．62）。按肿瘤类型亚组分析提示在胃癌和其他肿瘤存在相似的结果。结论IL-17Frs763780多态性可能并不增加肿瘤的易感性。     

A common genetic variant (97906C>A) of DAB2IP/AIP1 is associated with an increased risk and early onset of lung cancer in Chinese males

DOC-2/DAB2 interactive protein (DAB2IP) is a novel identified tumor suppressor gene that inhibits cell growth and facilitates cell apoptosis. One genetic variant in DAB2IP gene was reported to be associated with an increased risk of aggressive prostate cancer recently. Since DAB2IP involves in the development of lung cancer and low expression of DAB2IP are observed in lung cancer, we hypothesized that the variations in DAB2IP gene can increase the genetic susceptibility to lung cancer. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we investigated the association between two common polymorphisms in DAB2IP gene (-1420T>G, rs7042542; 97906C>A, rs1571801) and the risk of lung cancer. We found that compared with the 97906CC genotypes, carriers of variant genotypes (97906AC+AA) had a significant increased risk of lung cancer (adjusted odds ratio [OR] = 1.33, 95%CI = 1.04-1.70, P = 0.023) and the number of variant (risk) allele worked in a dose-response manner (P(trend) = 0.0158). Further stratification analysis showed that the risk association was more pronounced in subjects aged less than 60 years old, males, non-smokers, non-drinkers, overweight groups and in those with family cancer history in first or second-degree relatives, and the 97906A interacted with overweight on lung cancer risk. We further found the number of risk alleles (97906A allele) were negatively correlated with early diagnosis age of lung cancer in male patients (P = 0.003). However, no significant association was observed on the -1420T>G polymorphism. Our data suggested that the 97906A variant genotypes are associated with the increased risk and early onset of lung cancer, particularly in males.     

Cytochrome P4501A1 and microsomal epoxide hydrolase gene polymorphisms: gene-environment interaction and risk of prostate cancer

The role of low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear. Most procarcinogens require metabolic activation by CYP4501A1, whereas microsomal epoxide hydrolase (mEH) is involved in the detoxification. In our case-control study, we assessed whether CYP1A1 and mEH susceptibility genotypes, tobacco use, and age factors contribute to PCa risk. One hundred thirty patients with PCa and 140 control subjects were analyzed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method from genomic DNA samples. Binary logistic regression model was used for assessing differences in genotype prevalence and their association between patient and the control group. T/C polymorphism of CYP1A1 gene revealed significant association with the tobacco users (p < 0.005) for PCa risk. Our results demonstrated significant association with exon 3 variant genotypes of the mEH alone or in combination with tobacco users (p < 0.005), whereas in exon 4 genotypes, no association was observed. Haplotype analysis projected significant associations with very slow haplotypes of mEH gene (OR = 2.48, 95% CI = 1.41-4.38, p = 0.002). In conclusion, our study demonstrated that exon 3 of mEH and CYP1A1 T/C gene polymorphism are predisposing risk factors for susceptibility of sporadic PCa in northern India. It also suggests that a combination of smoking plays a significant role in modified PCa risk on the study population, which means that smokers carrying susceptible genotypes may be subjected to higher risk than those carrying nonsusceptible genotypes.     

Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in North Indian population

BACKGROUND:

Inherited polymorphisms of XPD and XPC genes may contribute to subtle variations in NER DNA repair capacity and genetic susceptibility to development of urological cancer such as prostate and bladder cancer.

MATERIALS AND METHODS:

We genotyped four Single Nucleotide Polymorphs (SNPs) of the DNA repair gene XPD and XPC in 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 healthy controls from the same area. XPD Exon 10 (G>A) by amplification refractory mutation system and Exon 23 (A>C), XPC Intron 9 (Ins/Del) and Exon 15 (A>C) were genotyped by PCR-RFLP.

RESULTS:

Variant genotype of XPC demonstrated association with PCa as well as in BC (P, 0.013; P, 0.003). Combined genotype (GA+AA) revealed association with PCa and in BC (P, 0.012, P, 0.002). Variant allele also demonstrated risk in both the cancer. Diplotype of XPD and XPC was associated with a significant increase in PCa and BC risk. Variant (+/+) genotype of XPC intron 9 shown increased risk with PCa and in BC (P, 0.012; P, 0.032). CC genotype of XPC exon 15 revealed increase risk (P, 0.047) with PCa not in BC. In clinopathological grade variant allele of XPC intron 9 and 15 demonstrated risk with high grade of tumor and bone metastasis of PCa. In BC variant allele of XPD exon 10 and 15 also shown association with tumor grade. XPC intron 9 influences the risk of BC in former tobacco users in BC.

CONCLUSIONS:

Our result support that SNPs in XPD and XPC gene may reduce NER repair capacity and play a major role for PCa and BC in North India.     

Interleukin-4 -590T/C polymorphism influences the susceptibility to nonsmall cell lung cancer

Lung cancer is the leading cause of cancer mortality worldwide. Nonsmall cell lung cancer (NSCLC) accounts for most of these cases. Interleukin 4 (IL-4) is a typical pleiotropic T helper 2 cytokine and plays crucial roles in tumor immunology. IL-4 gene -590T/C polymorphism has been shown to be associated with different autoimmune diseases and cancers. The present study evaluated the correlation between this polymorphism and the susceptibility to NSCLC in the Chinese population. The IL-4 variant -590T/C was detected by polymerase chain reaction-restriction fragment length polymorphism in 1072 NSCLC cases and 1126 age-matched healthy controls. Data were analyzed using the Chi-square test. Results showed that frequencies of IL-4 -590 TC, CC genotype, and -590 C allele were significantly lower in patients with NSCLC than in healthy controls (odds ratio [OR]=0.77, 95% confidence interval [CI] 0.64-0.93, p=0.006; OR=0.54, 95% CI 0.38-0.76, p=0.0004; and OR=0.72, 95% CI 0.62-0.83, p=1.1 × 10(-5), respectively). Our data suggest that the -590T/C polymorphism of the IL-4 gene is associated with a decreased susceptibility to NSCLC.     

Impact of genotyping on outcome of prostatic biopsies: a multicenter prospective study

Single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk and tumor aggressiveness in retrospective studies. To assess the value of genotyping in a clinical setting, we evaluated the correlation between three genotypes (rs1447295 and rs6983267[8q24] and rs4054823[17p12]) and prostatic biopsy outcome prospectively in a French population of Caucasian men. Five hundred ninety-eight patients with prostatic-specific antigen (PSA) >4 ng/mL or abnormal digital rectal examination (DRE) participated in this prospective, multicenter study. Age, familial history of PCa, body mass index (BMI), data of DRE, International Prostate Symptom Score (I-PSS) score, PSA value and prostatic volume were collected prospectively before prostatic biopsy. Correlation between genotypes and biopsy outcome (positive or negative) and Gleason score (≤6 or >6) were studied by univariate and multivariable analysis. rs1447295 and rs6983267 risk variants were found to be associated with the presence of PCa in univariate analysis. rs6983267 genotype remained significantly linked to a positive biopsy (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.06-2.59, P = 0.026) in multivariable analysis, but rs1447295 genotype did not (OR = 1.47, 95% CI: 0.89-2.43, P = 0.13).When biopsy outcome was stratified according to Gleason score, risk variants of rs1447295 were associated with aggressive disease (Gleason score ≥7) in univariate and multivariable analysis (OR = 2.05 95% CI: 1.10-3.79, P = 0.023). rs6983267 GG genotype was not related to aggressiveness. The results did not reach significance concerning rs4054823 for any analysis. This inaugural prospective evaluation thus confirmed potential usefulness of genotyping PCa assessment. Ongoing clinical evaluation of larger panels of SNPs will detail the actual impact of genetic markers on clinical practice.     

Interaction between hypertension and HSP70 variants increase the risk of cerebral ischemia in Chinese Han population: An association study

Cerebral infarction has become one of the leading diseases and a major mortality factor around the world. Atherosclerosis is recognized as one of the important causes of ischemic stroke. Recently, accumulating evidences have indicated that the anti-inflammatory and anti-apoptotic functions of the HSP70 family play an important role in cerebral ischemia. However, the association between HSP70 SNPs and ischemic stroke was also not well established. We chose 101 cases of cerebral ischemia and 100 healthy people from the Chinese Han population as our study subjects, and PCR-RFLP was employed to analyze HSP70 polymorphisms: HSP70-1+190G/C, HSP70-2+1267A/G and HSP70-hom+2437T/C. There were no significant differences in + 1267A/G allele or genotype frequencies between patients with stroke and healthy controls. However, genotypes of + 190CG and + 2437TT were differentially distributed between the patients and controls. A significant difference of T allele distribution in the HSP70-hom+2437T/C site was observed. Logistic regression analysis indicated that genotypes of + 190CG, + 2437TT and T allele in HSP70-hom were risk factors of ischemic stroke. Moreover, the study has formulated that the interactions between hypertension and + 190CG or + 2437TT may increase the risks of ischemic stroke. The results from this study have suggested a clinical indicator for assessing the possibilities of cerebral stroke, and supply basis to clinicians to give precaution to people who are at risk of stroke.     

Association between heat-shock protein 70 gene polymorphisms and DNA damage in peripheral blood lymphocytes among coke-oven workers

Hsp70 has been shown to act as a chaperone and be associated with cytoprotection against DNA damage caused by environmental stresses. However, it is unknown whether genetic variation in HSP70 plays a role in stress tolerance and cytoprotection against DNA damage. We determined the frequencies of three polymorphisms, HSP70-1 G190C, HSP70-2 G1267A, and HSP70-hom T2437C from 251 steel-plant workers exposed to coke-oven emission and 130 controls. We estimated the association between the HSP70variants/haplotypes and the levels of DNA damage in their peripheral blood lymphocytes detected by single-cell gel electrophoresis assay. Our results showed that overall coke-oven workers had higher levels of the Olive tail moment (Olive TM) (1.27+/-1.12) than that of the controls (0.56+/-0.99, P<0.001). Coke-oven workers with the HSP70-1 C/C genotype had higher levels of Olive TM (2.19+/-0.65), compared with HSP70-1 G/C and G/G carriers (Olive TM=1.34+/-1.09 and 1.14+/-1.08, respectively, P=0.022 and 0.003, respectively). However, the HSP70-2 G1267A and HSP70-hom T2437C polymorphisms were not associated with the levels of Olive TM (P=0.929 and 0.795, respectively). Haplotype analysis showed that carriers of TCG/TCG haplotype pairs had the highest levels of Olive TM among both the exposed subjects (2.04+/-0.59) and the controls (0.81+/-0.59). Our results suggest that the individuals with the homozygous HSP70-1 C/C genotype among the coke-oven workers may be susceptible to DNA damage.     

Genetic variants in the microRNA machinery gene GEMIN4 are associated with risk of prostate cancer: a case-control study of the Chinese Han population

Single-nucleotide polymorphisms located in the microRNA biogenesis pathway could alter the risk for developing prostate cancer. The present study was intended to identify common genetic variants responsible for prostate cancer susceptibility in the GEMIN4 gene. The high-resolution melting method was used to genotype seven polymorphisms (rs7813, rs4968104, rs3744741, rs2740348, rs1062923, rs910925, and rs910924) in the GEMIN4 gene in 300 prostate cancer patients and 244 matched controls. The encouraging discovery in this study was in the rs2740348. Patients carrying the variant heterozygote GC genotype in the rs2740348 were at a 36% decreased risk of prostate cancer (odds ratio [OR] = 0.64; 95% confidence interval [CI] = 0.42, 0.99). Similarly, this variant allele carrier showed significant risk for prostate cancer (OR = 0.64). In addition, subjects carrying the homozygote TT genotype in the rs7813 had a significantly increased risk of prostate cancer (OR = 2.53, 95% CI = 1.07, 6.28). Two common haplotypes were found to be associated with decreased risk of prostate cancer. In the subgroup analysis, higher risk of more severity of prostate cancer (clinical stage III and IV) was observed in individuals with the rs7813 TT genotype (OR = 2.64, 95% CI = 1.02, 7.64), while lower risk of more severity of prostate cancer was observed in individuals with the rs3744741 T allele (OR = 0.69, 95% CI = 0.50, 0.96). Overall, our study provides substantial support for the association between the GEMIN4 gene and the risk of prostate cancer.