However, there are some limitations in this meta-analysis. First of all, even though we performed subgroup analyses stratified by ethnicity and control source, the heterogeneity for GSTM1 polymorphism among the studies was extreme. It suggested that there were other potential confounding factors inthe included studies, such as the genotyping error, selection bias, or population-specific gene-gene or gene-environment interaction, allelic heterogeneity, or chance [88,89]. Although evidence of heterogeneity exists, it was found through sensitivity analysis that studies contribute to the heterogeneity do not significantly alter the estimate of overall odds ratio. Secondly, only published studies were included, therefore the publication bias may have been occurred. The Egger’s test provided statistical evidence of that. We observed the publication bias when only considered studies about theassociationbetween GSTT1 polymorphism and PCa risk, but did not find it inthe studies about the PCa risks with GSTM1 and GSTP1 polymorphisms. It is known that positive results usually have a greater probability of being published, and such bias may occur when studies with null or unexpected results. In addition, we also performed the trim-and-fill andthe corrected OR was the same as the uncorrected one. Therefore, our result of GSTT1 null genotype was reliable and stable to some extent. Thirdly, the overall outcomes were based on unadjusted effect estimates. Although the cases and controls were matched on age, sex and residence in all studies, these confounding factors might slightly modify the effective estimates and a more precise evaluation needed to be adjusted by the potentially suspected factors. Finally, as the meta-analysis remains a retrospective research which is subject to the methodological deficiencies ofthe included studies, we tried to develop a detailed protocol before initiating the study, and then performed an explicit method for study researching, selection, data extraction and data analysis to minimize the likelihood of bias.
Prostatecancer is the second most frequent malignancy diagnosed in adult men. Androgens are considered the primary growth factors for prostate normal andcancer cells. However, other non-androgenic growth factors are involved inthe growth regulation ofprostatecancer cells. Theassociationbetween IGF-I andprostatecancerrisk is well established. However, there is no evidence that the measurement of IGF-I enhances the specificity ofprostatecancer detection beyond that achievable by serum prostate-specific antigen (PSA) levels. Until now, there is no consensus on thepossibleassociationbetween IGFBP-3 andprostatecancerrisk. Although not well established, it seems that high insulin levels are particularly associated with riskof aggres- sive prostatic tumours. This review describes the physiopathological basis, epidemiological evidence, and animal models that support theassociationofthe IGFs family and insulin with prostatecancer. It also describes the potential therapies targeting these growth factors that, inthe future, can be used to treat patients with prostatecancer. Arq Bras Endocrinol Metab. 2009;53(8):969-75
DNA repair deregulation is a crucial factor inthe multistep process of carcinogenesis, andthe ERCC5 gene is a vital component ofthe DNA repair machinery. It has been observed that deficiency of ERCC5 may result in severe autosomal recessive diseases including XP, CS and TTD  characterized by solar hypersensitivity ofthe skin, high predisposition for developing cancers (mainly epithelial and melanoma) on areas exposed to sunlight. Furthermore, studies have suggested that ERCC5 SNPs are associated with development of some cancers, such as breast cancer  and smoking-related cancers [23,24]. These suggest a possible link betweenthe ERCC5 function and development ofcancer. The biological mechanisms ofthe ERCC5 gene in carcinogenesis may be complicated, among which nsSNPs, leading to an amino acid change inthe protein product and modulating the individual DNA repair capacity phenotype [113,114], may account for some ofthe known genetic variations related to riskof cancers. However, our meta-analysis suggests that there is no statistical evidence for an associationbetweenthe ERCC5 Asp1104His polymorphism and overall cancerrisk, which is consistent with the previous two meta-analyses conducted in breast cancerand melanoma, respectively. The former included some studies departure from HWE inthe control population, andthe latter only contained three studies. Although we excluded the inappropriate studies and expanded the sample size, the null results were not altered. Furthermore, as far as our knowledge is concerned, none ofthe SNPs in NER have ever been identified as susceptibility locus inthe published genome-wide association studies (GWAS) for common diseases including cancers based on common SNPs, which are similar to our results. This is a challenge to the theory of common variants and common diseases . It is likely that, as NER genes are considered susceptibility genes, the role of NER variants incancer development may be dependent on the degree of exposures that cause damage to DNA. Therefore, without detailed information about such exposures for further adjustment or stratification, the results ofthe observed associations may be either biased or masked. For example, XP patients can drastically reduce riskof developing skin cancer by avoiding exposure to sunlight. Another possibility is that the common
Inthe present study, the majority of men was white and less than 50 years old. According to recent data, the recommendation of PSA scre- ening in this specific population remains contro- versial. It is well established that age, race, and family history ofprostatecancer increase theriskof developing and dying ofthe disease. Bla- ck men are approximately twice as likely to die ofprostatecancer than other men, andthe rea- son for this disparity is unknown (16). Prelimi- nary results from PIVOT (ProstateCancer Inter- vention Versus Observation Trial), in which 30% of enrollees were black, found no difference in outcomes due to treatment ofprostatecancerin these men compared with other races (17). Des- pite controversies, the 2013 American Urological Association Guidelines recognized that the PSA screening test might benefit certain subgroups of younger men with high riskofprostate can- cer. However, this report suggests that patients should be informed about the potential harmful effects of these tests as well as the benefits of screening at an earlier age. Physicians should be aware that there are no comparative data andthe best approach for this specific group is not well established (18).
with prostatecancer than their neighboring SNPs replicated in Phase I. Theassociationof Rs16988102 with prostatecancer was also supported by strong associations of multiple surrounding SNPs with prostatecancer. Rs16988102 is located in 5 9 upstream ofthe C2orf43 gene. The distance between rs16988102 and rs13385191 is more than 300 kb, which is much longer than general distance of LD. Thus, we prefer to claim the rs16988102 as a risk locus for prostatecancer independent to rs13385191. This is in accordance with the significantly lifted OR by adding rs16988102 to therisk model ofprostatecancer which only took the variation of rs13385191 into account. Rs9489065 is located in Figure 1. LD maps ofthe tested SNPs andassociation test results for the loci around rs13385191 in Phase II.
Associations between smoking andcancer, due to the diversity of chemical products that comprise the tobacco, are considered as genotoxic and carcinogenic. 16,19 Smoking is associated with the occurrence of several malignant diseases inthe oral cavity, pharynx, esophagus, stomach, pancreas, colon, rectum, liver and biliary tract, kidneys, bladder, breast, cervix, vulva, myeloid leukemia, among others. 21-22 Numerous evidences indicate an associationbetween active and passive smokers with cancer. However, this correlation is not yet well established due to possible interactions between smoking, alcohol and influences of hormonal factors, 50,52 one aspect that can also be found inthe presented data.
In our data example, we obtained confirmatory evidence oftheassociationofthe HOXB13 G84E mutation with prostatecancer, and provided age-specific risks for developing prostatecancer for mutation carriers in a large, prospective cohort. We also provided evidence that the G84E mutation exhibits a pleiotropic effect on numerous other cancers, though sample sizes made it difficult to determine precisely which cancers are involved. Consistent with the hypothe- sis of pleiotropy, we also provided suggestive evidence that the mutation exhibits a stronger asso- ciation in individuals with multiple cancers, both involving prostatecancerand independent ofprostatecancer. Multiple cancers inthe same individual will most often arise independently and may reflect pleiotropic events, though in some cases may be due to metastasis. A shared genetic basis among cancers may be supported by HOXB13’s role in embryonic development and body patterning [20,43,44]. HOXB13 is particularly expressed intheprostate , where it physically interacts with the androgen receptor, which is important for growth and regulation of differentia- tion in normal cell biology. Thus, HOXB13 may impact the carcinogenic process via its action on growth and development. More work is needed to examine the biological mechanisms and effects that the mutation has on the function ofthe HOXB13 gene. Two key factors made this investiga- tion possible: a very large genotyped cohort with information on multiple cancers and our ability to impute the G84E mutation using a custom reference panel.
The aim of this study was to evaluate theassociationbetweenprostatecancer (PCa) and Human papillomavirus (HPV) infection inthe Mexican population. We studied 356 paraffin-embedded tissues from unrelated Mexican men with PCa or benign prostatic hyperplasia (BPH), with the latter serving as control. HPV detection was performed by polymerase chain reaction (PCR) using universal primers, and viral genotypes were detected using sequencing or multiplex PCR. Light microscopy analyses enabled the identification of koilocytes in samples subsequently analyzed for HPV detection by in situ PCR and for p16-INK4A expression by immunohistochemistry. The results showed that high risk- (HR) HPVs were detected in 37/189 (19.6%) PCa specimens compared to 16/167 (9.6%) of BHP speci- mens (odds ratio 2.3; 95% CI= 1.2 to 4.3; p=0.01). These data suggest HR-HPV may play a role in PCa. HPV 52 and 58 were the most frequent genotypes (33 and 17%, respectively) detected inthepopulation studied. Koilocytes were detected in all in situ PCR-HPV-positive samples, representing a pathognomonic feature of infection, and we ob- served the overexpression of p16-INK4A in HPV-positive samples compared to HPV-negative samples, indirectly suggesting the presence of HR-HPV E7 oncoprotein. These results suggest that HPV infection plays an important role inprostatecancer development.
fluence in PSA (like history of prostatitis or re- cent urologic procedures). Thus, the reasons for these assays in young patients were not clear, affecting the representativeness of data. Other limitations are the retrospective nature of this study andthe different numbers of individuals included per age. However, considering our ou- tcomes, we might consider evaluating all these subjects as a single group. Finally, even after analyzing the values > 4.0 ng / mL separately of our main analysis, we still have several ca- ses of outliners at all ages. Nevertheless, they represented few patients when considered the universe ofthe study.
Triple-negative breast cancer (TNBC) is defined by the lack ofthe expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It is characterized by aggressive behavior, poor prognosis and lack of targeted therapies. MicroRNA (miRNA) as a novel modulator of gene expression has played an important regulatory role inthe malignancy. Dysregulation and/or mutation ofthe miRNAs may also contribute to the TNBC susceptibility since it is associated with the expression of ER, PR and HER2. Single nucleotide polymorphisms (SNPs) in miRNAs may be extremely relevant for TNBC. We tried to validate the hypothesis that genetic variations in miRNA are associated with TNBC development, and identify candidate biomarkers for TNBC susceptibility and clinical treatment. We screened the genetic variants in all miRNA genes listed inthe public database miRBase and NCBI. A total of 23 common SNPs in 22 miRNAs, which tagged the known common variants inthe Chinese Han people with a minor allele frequency greater than 0.05, were genotyped. This case-control study involved 191 patients with TNBC and 192 healthy female controls. Frequencies of SNPs were compared between cases and controls to identify the SNPs associated with TNBC susceptibility. No significant association was found between TNBC riskandthe SNPs inthe miRNA genes inthe Chinese Han people (P.0.05), but this warrants further studies.
(P = 0.007) and rs2740348 (P = 0.044) enhanced the reliability of our results. We did not show the results for HWE in Table 2 because all collected data were related to the GG and GC + CC genotypes, and HWE could not be calculated. However, the authors of these studies indicated that all gene polymorphisms ofthe control group conformed to HWE. Next, we investigated the Gemin3 rs197412 SNP, which is a key indicator of renal cell carcinoma. In this meta-analysis, however, rs197412 was not associated with increased cancerrisk. In addition, we searched for articles related to the Gemin3 rs197414 and rs197338 SNPs, andthe Gemin4 rs3744741 and rs4968104 SNPs. However, we identified fewer than five articles, which was insufficient for us to evaluate the precise relationship between these SNPs andcancerrisk. However, we found several articles that reported an associationbetween Gemin polymorphisms and several chronic diseases, such as hepatitis B (Shang et al., 2014). The relationship between Gemin and these chronic diseases, as well as cancer, should be investigated further.
various tissue, including lung tissue and overexpress in cisplatin- resistant cell lines, encodes an enzyme—cleft lip and palate trans- membrane 1-like that may be associated with apoptosis . In consideration ofthe premises, this associated SNP rs402710 has attracted many investigators’ attention from multiple countries and regions. Several follow-up replication studies have resound- ingly replicated the significant associationofthe SNP with lung cancerrisk, in Caucasian [14,15,16] and Asian [16,17,18,19] population. However, some other replication studies showed the inconsistent outcomes [20,21,22]. Two Chinese replication studies failed to identify the similar effect in separate Chinese population [20,21], which may be due to the small sample size. Additionally, owing to the phenomena ‘‘winner’s curse’’ that the effect sizes of initial positive study are usually overestimated, the following replication studies are possibly to be underpowered and then very likely to fail if the necessary sample sizes are based on the initially overestimated effect sizes . Nevertheless, meta-analysis, a method combining data together to make sample size exponential growth to get enough power, can clarify inconsistent results in genetic association studies . Therefore, we conducted a case- control study to examine theassociationbetween rs402710 and lung cancerriskin Chinese population, after that, a meta-analysis combining previously published studies and our current study was conducted to provide a more precise estimate of this association.
SNPs are the most common genetic variations which influence interindividual predisposition to breast carcinogenesis and prog- nosis . SNP association analysis has provided valuable information about the genetic susceptibility of breast cancer . The human CD28 gene is located inthe chromosome 2q33 region. Polymorphisms inthe CD28 gene were previously shown to be genetically associated with autoimmune diseases, such as rheumatoid arthritis and Bechet’s disease [21,22]. Several compelling reports characterized theassociationbetween this susceptibility loci and cervical cancerriskin different ethnic groups [23,24,25,26,27]. Chen et al.  and Ivansson et al.  found that the rs3116496 TT genotype was associated with a low riskof cervical cancerin a Chinese Han and a Swedish population, respectively. Conversely, Guzman et al.  observed that the rs3116496 TT genotype was associated with an increased cervical cancerrisk when combined with the IFN+847AA genotype, in a Brazilian population. Pawlak et al.  demonstrated that rs3116496 was not correlated with cervical squamous cell carcinoma, when taking all evaluated patients into consideration. No case-control study of CD28 gene polymorphisms in sporadic breast cancer has been reported. Given theassociationbetween polymorphisms inthe CD28 gene region and cervical cancerriskin different populations, as well as the potential role of costimulatory molecules in carcinogenesis, we examined theassociationbetween CD28 polymorphisms and breast cancerriskand tumor pathology. Our data provides the first evidence for the involvement ofthe human CD28 gene in breast cancer.
Relative advantage is defined as the extent to which a person views an innovation as offering an advantage over previous ways of performing the same task (Roger, 1983; Agarwal & Prasad, 1997). Because Internet banking services allow customers to access their banking account from any location 24 hours a day and 7 days a week, it provides an enormous advantage and convenience to users (Tan & Teo, 2000). It also gives customers greater control over managing their finances, as they are able to check their accounts easily. Besides, a customer’s Internet experience, his or her banking needs can affect his adoption. As there are more financial products and services, it is expected that individuals with many financial accounts and who subscribe to many banking services will be more inclined to adopt Internet banking. Tan and Teo (2000) has reported that potential adopters of Internet banking services are likely to own multiple banking accounts and subscribe to various banking services. Rogers argues that potential adapters, who are allowed to experiment with an innovation will feel more comfortable with the innovation and are more likely to adopt it. Thus, if customers have the opportunity to try the innovation, certain fears ofthe unknown may be minimized. Government policy could also aid or hinder Internet diffusion (Mbarika, 2002). This is consistent with the national systems of innovation theory that posits that government policies may encourage or mandate technology development and adoption (King et. al., 1994; Wolcott et. al., 2001). Tan and Teo (2000) suggest that the greater the extent of government support for Internet commerce, the more likely Internet banking will be adopted, thus, confirming Goh’s (1995) suggestion that governments can play an interventionist and leading role inthe diffusion of innovation. Potential users in turn would view new applications such as Internet banking services more favorably and hence be more like to use them. Thus, the second alternative hypothesis is:
We compared baseline demographic and lifestyle characteristics ofprostatecancer cases and controls by student t test for continuous variables and chi-square test for categorical variables. Serum concentrations of finasteride were categorized based on clinically defined cut points. Lo- gistic regression was used to calculate ORs and 95% CIs for riskof total prostatecancer, and polytomous logistic regression was used to calculate ORs and 95% CIs of both low-grade and high-grade prostate cancers. The polytomous regression with a generalized logit link permits a model including both low-grade and high-grade cancers as outcomes inthe same model, con- trasted with no cancer. Tests for linear trend for finasteride concentration were based on an or- dinal variable corresponding to rank (lowest to highest). Model covariates were carefully selected based on a priori information about potential confounding as well as diagnostic proce- dures completed as part of our modeling exercises. Final covariates included age, race (white/ black/others), time of day of finasteride blood draw, and family history ofprostatecancer. To determine theassociationbetween single SNP and finasteride levels among whites, mean con- centrations of finsteride were calculated for each allele, and p-values were calculated using line- ar regression adjusted for age and alcohol consumption. All statistical tests were two-sided, with P < 0.05 considered statistically significant. SAS (version 9.2) and R (version 2.15.1) were used for all statistical analyses. Haploview v4.1 was used for assessing LD patterns and haplo- type association statistics . Haplotype blocks were determined using the algorithm of Ga- briel et al .
The essence of social economy is the inclusive function ofthe labor market through which the different forms of social economy that exist inthe member states can play a role inthe overcoming the crisis, especially inthe creating of jobs, including in social services field Opinion ofthe European Economic and Social Committee on the post‐ 2010 Lisbon Strategy 9, p. .
A pilot study was conducted with 10% ofthe total sample, involving students who were not participating inthe main study. The methodology showed to be adequate, with no need for adjustments. The data collected were inserted into a spreadsheet specially designed for this study where they were analyzed using SPSS 18.0 software. Bivariate and multivariate analyzes were performed using Poisson log-linear regression with robust estimator in order to determine theassociationbetweenthe dependent variable (OIDP> 0) andthe independent variables (dental trauma, age, sex, dental caries and malocclusion) with a significance level of p <0.05. Raw and adjusted prevalence ratios (PR) and their respective confidence intervals (95%) were also estimated.
Results: JLS was observed in 56/5881 patients (0.9%), mainly linear morphea subtype. EI was observed in 23/56(41%) of JLS patients. Eight(35%) of 23 EI patients with JLS were symptomatic and presented heartburn(5/8), solid and liquid dysphagia(3/8), nausea and epi- gastralgia(1/8). The frequency of any cumulative extracutaneous manifestations (calcinosis, arthritis/arthralgia, central nervous system, interstitial pneumonitis, mesangial nephritis and/or arrhythmia) was significantly higher in JLS patients with EI compared to those with- out this complication (56% vs. 24%, p = 0.024). No differences were evidenced in demographic data, JLS subtypes andin each extracutaneous manifestation in both groups (p > 0.05). The frequency of methotrexate use was significantly higher in JLS patients with EI compared to those without (52% vs. 12%, p = 0.002). Autoantibody profile (antinuclear antibodies, anti- SCL-70, rheumatoid factor, anticentromere, anti-cardiolipin, anti-Ro/SSA and anti-La/SSB) was similar in both groups (p > 0.05).
On the 3rd to the 5th day of a spontaneous menstrual cycle or a progesterone-induced with- drawal bleeding from PCOS patients, heparinized whole-blood samples were gathered inthe morning after fasting overnight using tubes containing ethylenediaminetetraacetate (EDTA) (as anticoagulant). Then, every subject had a physical examination including weight, height, waist and hip circumference measurement. The hip circumference was the largest hip size and waist circumference was measured nearby umbilicus when subjects were standing. The plasma ofthe whole-blood samples was removed and stored at -80°C before analysis. Genomic DNA was extracted from the heparinized venous blood leukocytes of PCOS patients and controls using standard phenol-chloroform method. Follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T), estradiol (E2), dehydroepiandrosterone-sul- fate (DHEAS) and fasting insulin (FINS) were detected by chemiluminescence assay. Fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) were detected by hexokinase- method. The following formulas were adopted to calculate some parameters: HOMA-B% (homeostasis model assessment-B) = 20 × fasting insulin / (fasting plasma glucose-3.5). HOMA-IR (essment-Insulin resistance) = fasting insulin × fasting plasma glucose/22.5 (normal range: < 1.8). QUICKI (quantitative insulin sensitivity check index) = 1 / (logFINS + logFPG (mg/dl)) (normal range: 0.375). BMI = weight (kg) / height 2 (m 2 ).