Folate and choline metabolism gene variants and development of uterine cervical carcinoma

ObjectiveIt has been reported that aberrant DNA methylation can be associated with HPV infection and cervical tumorigenesis. The aim of this study was to evaluate the possibility that polymorphic variants of genes that may affect DNA methylation status are associated with the risk of cervical cancer in the Polish population.Design and methodEmploying PCR-RFLPs and HRM analyses, we examined the prevalence of BHMT Arg239Gln (rs3733890), MTR Asp919Gly (rs1805087), MTHFR Ala222Val (rs1801133), MTHFD1 Arg653Gln (rs2236225) and MTRR Ile22Met (rs1801394) genotypes and alleles in patients with advanced cervical cancer (n = 124) and controls (n = 168).ResultsThe odds ratio (OR) for BHMT Gln/Gln genotype was 0.433 (95% CI = 0.1780–1.054; p = 0.0602). The OR for patients having the BHMT Arg/Gln or Gln/Gln genotypes was 0.579 (95% CI = 0.3622–0.924; p = 0.0216). We also observed a significantly higher frequency of the BHMT 239Gln allele in controls than in patients, p = 0.0165. The genotype and allele frequencies of the MTR Asp919Gly, MTHFR Ala222Val, MTHFD1 Arg653Gln and MTRR Ile22Met gene variants did not display statistical differences between patients with cervical cancer and controls. We also did not find a significant association between the distribution of any genotypes or alleles and cancer characteristics.ConclusionOur results might suggest the protective role of the BHMT 239Gln variant in cervical cancer incidence.     

The HLA-DQB1 gene polymorphisms associated with cervical cancer risk: A meta-analysis

Human leukocyte antigens (HLA) alleles may affect the development of cervical cancer through immunologic control of human papillomavirus (HPV). The association between HLA-DQB1 alleles and risk of cervical cancer has been extensively studied, but the results obtained remain inconsistent. To explore a more extensive role of HLA-DQB1 alleles on cervical cancer risk, we carried out a meta-analysis including 4862 cases and 8988 controls from 22 published studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The overall results suggested that HLA-DQB1*02 (OR = 0.91, 95% CI = 0.82–0.99), *03 (OR = 0.85, 95% CI = 0.74–0.97) and *0603 (OR = 0.62, 95% CI = 0.53–0.72) had a significantly association with decreased cervical cancer risk. In contrast, DQB1*05 (OR = 1.18, 95% CI = 1.01–1.38), *0301 (OR = 1.14, 95% CI = 1.06–1.23) and *0402 (OR = 1.31, 95% CI = 1.04–1.64) conferred a significantly higher risk to cervical cancer. Moreover, a significantly association with increased or decreased cervical cancer risk was found among Europeans and Asians after stratification of the HLA-DQB1 alleles by ethnicity. These findings supported that the HLA-DQB1 alleles may contribute to genetic susceptibility of cervical cancer. Further studies with a greater number of cases are expected to confirm our results.     

CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD

BackgroundThe genetic susceptibility to chronic obstructive pulmonary disease (COPD) depends on detoxification and antioxidant enzymes, which detoxify cigarette smoke reactive components that, otherwise, generate oxidative stress.MethodsIn a case–control study of 346 subjects with and without COPD, we examined the polymorphisms 462Ile/Val, 3801T/C of CYP1A1, ?3860G/A of CYP1A2 and ?930A/G, 242C/T of CYBA individually or in combination and their contribution to oxidative stress markers by measuring malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx).ResultsCOPD patients had significantly increased MDA concentration (p < 0.001) and decreased CAT activity, GSH concentration, GPx activity (p ≤ 0.01). The patients were over-represented by the alleles 462Val, 3801C of CYP1A1 and ?930G, 242C of CYBA (p < 0.001, p = 0.003, p = 0.030 and p = 0.031, respectively) and consequently the haplotypes of same alleles i.e. 462Val:3801C, 462Val:3801T and ?930G:242C (p = 0.048, p = 0.016 and p = 0.039, respectively). Similarly, CYP1A1 and CYP1A2 haplotypes, 462Val:3860G and 462Val:3801T:3860G were significantly over-represented (p = 0.001 and p = 0.003), respectively in patients. The same alleles-associated genotype-combinations between genes were more prevalent in patients. Of note, the genotypes, 462Ile/Val+Val/Val, 3801TC+CC of CYP1A1 and ?930AG+GG of CYBA associated with increased MDA concentration (p = 0.018, p = 0.045 and p = 0.017, respectively), decreased CAT activity (p < 0.0001, p = 0.080 and p < 0.0001, respectively) and GSH concentration (p < 0.0001, p = 0.0002 and p = 0.011, respectively) in patients.ConclusionThe identified alleles, its haplotypes and the genotype-combination along with increased oxidative stress, signify the importance in susceptibility to COPD.     

Prediction equation of hip external rotators maximum torque in healthy adults and older adults using the measure of hip extensors maximum torque

BackgroundThe use of predictive equation of muscular torque can reduce physical effort and time spent during evaluation.ObjectivesTo establish, validate, and test the accuracy of a prediction equation to estimate the hip external rotators (HER) torque in adults and older adults by means of hip extensors (HEX) torque measurement.MethodsEighty-three healthy adults (development set) were assessed to test the association of HEX and HER torques and to establish the prediction equation. A separate 36 adults and 15 older adults (validation sets) were assessed to test the ability of the equation to estimate HER torque. Hip isometric strength was assessed by a handheld dynamometer.ResultsSimple linear regression analysis revealed that HEX torque was associated with HER torque (r = 0.80; p < 0.0001), resulting in the following prediction equation: HER_torque= −0.02 + (0.58 * HEX_torque). Paired t-test revealed no difference between directly measured and predicted values of HER torque in adults (mean difference = 0.02; 95% CI = −0.115, 0.072) and older adults (mean difference = 0.05; 95% CI = −0.02, 0.12).ConclusionThe HEX and HER torques were strongly correlated. The prediction equation was valid, accurate, and can be used to estimate HER muscle strength in healthy adults and older adults, requiring only the direct measurement of HEX torque.     

The association between miR-146a gene rs2910164 polymorphism and gastric cancer risk: A meta-analysis

PurposeStudies have demonstrated that single nucleotide polymorphisms (SNPs) in miRNAs may lead to varying functional outcomes by altering miRNAs expression, even leading to the development of cancers. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to gastric cancer has been studied during the recent years, but the results are still inconclusive and inconsistent. We performed a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphism and the risk of gastric cancer.Materials and methodsThe databases of PubMed, MEDLINE and Web of Science were searched for suitable studies. A total of 8 published case–control studies on miR-146a rs2910164 polymorphism and gastric cancer risk including 4308 cases and 6370 controls were included.ResultsOverall, significant association was observed between rs2910164 and gastric cancer risk in allele model (OR = 1.11, 95% CI = 1.02–1.21); homozygote model (OR = 1.26, 95% CI = 1.10–1.43) and dominant model (OR = 1.21, 95% CI = 1.09–1.34). Stratified analysis by ethnicity showed significant association between rs2910164 polymorphism and gastric cancer susceptibility in Asians (OR = 1.10, 95% CI = 1.00–1.23 for G vs. C; OR = 1.25, 95% CI = 1.09–1.43 for GG vs. CC; OR = 1.19, 95% CI = 1.07–1.33 for GG vs. GC+CC, respectively). When stratified by genotyping methods and sample size, increased gastric cancer risk was only observed with the method by TaqMan and the sample size more than 1000.ConclusionIn summary, this meta-analysis indicated that miR-146a rs2910164 polymorphism was associated with the susceptibility to gastric cancer, especially in Asian population.     

Clinical significance of Stratifin,ERα and PR promoter methylation in tumor and serum DNA in Indian breast cancer patients

Objectives:The objective of this study was to determine the concordance of promoter methylation of stratifin, ERα and PR in tumor and circulating DNA in breast cancer patients and their association with clinicopathological parameters and disease prognosis.Design and methods:Methylation specific PCR were carried out to investigate the promoter methylation status of stratifin, ERα and PR in tumor and circulating DNA in 100 breast cancer patients in a prospective study. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.Results:Significant association was observed between promoter methylation of stratifin in tumors (61%) and paired sera (56%) (r = 0.78; p ≤ 0.001). Loss of stratifin expression was observed in 47% tumors and was associated with poor overall survival (p = 0.05). Significant correlation was observed between methylation status of ERα with PRB (p < 0.0001, OR = 20.8, 95% CI = 7.4–58.0) and stratifin (p = 0.003, OR = 2.0, 95% CI = 0.8–4.4).Conclusion:This study underscores the potential utility of serum DNA methylation of these genes as surrogate for tumor DNA methylation as a promising tool for cancer diagnosis.     

Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a Chinese population

ObjectiveCoronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methionine sulfoxide reductase A (MSRA: rs10903323 G/A) and vascular endothelial growth factor A (VEGFA: rs699947 C/A, rs2010963 G/C, and rs3025039 C/T) contribute to CAD susceptibility.Designs and methodsWe examined the association between the four polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS).ResultsWhen the MSRA rs10903323 GG homozygous genotype was used as the reference group, the GA and GA/AA genotypes were associated with a significantly increased risk of CAD (GA vs GG: adjusted OR = 1.36, 95% CI = 1.02–1.82, p = 0.038; GA/AA vs GG: adjusted OR = 1.33, 95% CI = 1.01–1.76, p = 0.042). The AA homozygous genotype was not associated with a risk of CAD. In the recessive model, when the MSRA rs10903323 GG/GA genotypes were used as the reference group, the AA homozygous genotype was not associated with a risk of CAD. Logistic regression analyses revealed that the VEGFA rs699947 C/A, VEGFA rs2010963 G/C, and VEGFA rs3025039 C/T polymorphisms were not associated with a risk of CAD.ConclusionsThese findings suggest that the functional MSRA rs10903323 G/A polymorphism is associated with CAD development. However, our results allow only a preliminary conclusion, which must be validated with a larger study of a more diverse ethnic population.     

GSTM1-null and GSTT1-null genotypes are associated with essential arterial hypertension in patients with type 2 diabetes

ObjectiveTo evaluate whether the genetic polymorphisms of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1), Ile105Val of the GSTP1 (rs947894), and the Val16Ala polymorphism of the MnSOD (rs4880) are associated with essential arterial hypertension (EAH) in Caucasians with type 2 diabetes.Design and methods1015 Slovenian subjects (Caucasians) with type 2 diabetes with/without EAH were enrolled in the cross-sectional study. Genotypes were determined by multiplex PCR amplification and PCR-restriction fragment length polymorphism method.ResultsIn the cross-sectional study, GSTM1-null genotype and GSTT1-null genotype were associated with EAH in subjects with type 2 diabetes (59.0% vs. 50.3%, p = 0.007; 28.5% vs. 20.7%, p = 0.008; consequently).ConclusionAfter adjustment for age, body mass index, and hsCRP level, GSTM1-null and GSTT1-null genotypes were found to be independent risk factors for the development of EAH in Slovenian patients with type 2 diabetes.     

Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans

BackgroundAssociations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors.MethodsWe genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database.ResultsWith a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P = 0.025, OR = 1.47, 95% CI = 1.05–2.06; P = 0.023, OR = 1.53, 95% CI = 1.06–2.22) and adults (P = 0.018, OR = 1.10, 95% CI = 1.02–1.19; P = 0.001, OR = 1.16, 95% CI = 1.06–1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P = 0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P = 0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found.ConclusionsFTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.     

Motivators and barriers to Latinas' participation in clinical trials: The role of contextual factors

ObjectiveLatinas are underrepresented in clinical trials despite the rise in Hispanic population. This study examines the factors associated with Latinas' willingness to participate in preventive breast cancer randomized clinical trials (RCTs).MethodsWomen self-identifying as Latina, over age 40, with no prior history of breast cancer were eligible. Using the Behavior Model for Vulnerable Populations, we administered a survey (n = 168) to assess predisposing (e.g., knowledge), enabling (e.g., trust) and need factors (e.g., risk perception). Intention to participate was defined using a lenient (maybe, probably or definitely) and a stringent criterion (probably and definitely). Chi-square tests and logistic regression models examined the associations of predisposing, enabling, and need factors with women's intentions to participate in RCTs.ResultsMost participants (74.9%) were monolingual Spanish-speaking immigrants. Most (83.9%) reported willing to participate in clinical trials using the lenient definition (vs. 43.1% under the stringent definition). Using the lenient definition, the odds of willing to participate in RCTs were significantly lower for unmarried women (OR = .25, 95% CI = .08–.79) and those with lower cancer risk perceptions (OR = .20, 95% CI = .06–.63), while being significantly higher for women with lower language acculturation (OR = 6.2, 95% CI = 1.8–20.9). Using the stringent definition, women who did not endorse a motivation to enroll to help family members (if they had cancer) had significantly lower odds to report intent (OR = .33, 95% CI = .13–.86).ConclusionMany RCTs may have limited generalizability due to the low representation of minorities. Culturally targeted interventions that address the importance of family for Latinos may ultimately increase their participation in RCTs.     

Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy

BackgroundCommon single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM).MethodsGenotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay.ResultsSignificantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P < 0.0001, OR = 1.730, 95% CI = 1.345–2.227, and P < 0.0001, OR = 1.794, 95% CI = 1.350–2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P = 0.0001 and P < 0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P = 0.451, OR = 1.102, 95% CI = 0.856–1.418).ConclusionsBoth the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.     

Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese

BackgroundImpaired ubiquitin–proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD).MethodsWe conducted a case–control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD.ResultsNo significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls ≥ 60 years of age (P = 0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals ≥ 60 years of age (OR = 0.61; 95% CI = 0.41–0.90, P = 0.010). This is also true for T allele (OR = 0.64; 95% CI = 0.44–0.91, P = 0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR = 0.42; 95% CI = 0.22–0.81, P = 0.009) and UCHL1 C-carrying genotype (OR = 0.67; 95% CI = 0.47–0.97, P = 0.032).ConclusionsOur results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people ≥ 60 years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.     

Chinese herbal medicine Kuntai capsule for treatment of menopausal syndrome: a systematic review of randomized clinical trials

ObjectivesKuntai capsule has been widely used for the treatment of menopausal syndrome in China for long time. We conducted this review to assess efficacy and safety of Kuntai capsule for the treatment of menopausal syndrome.MethodsWe searched studies in PubMed, ClinicalTrials, the Cochrane Library, China National Knowledge Infrastructure Database(CNKI), China Science and Technology Journal Database (VIP), Wan fang Database and Chinese Biomedical Literature Database(CBM) until November 20, 2014. Randomized trials on Kuntai capsule for menopausal syndrome, compared with placebo or hormone replacement therapy (HRT) were included. Two reviewers independently retrieved the randomized controlled trials (RCTs) and extracted the information. The Cochrane risk of bias method was used to assess the quality of the included studies, and a Meta-analysis was conducted with Review Manager 5.2 software.ResultsA total of 17 RCTs (1455 participants) were included. The studies were of low methodological quality. Meta-analysis indicated that there was no statistical difference in the Kupperman index (KI) [WMD = 0.51, 95% CI (−0.04, 1.06)], the effective rate of KI [OR = 1.21, 95% CI (0.72, 2.04)], E2 level [WMD = −15.18, 95% CI (−33.93, 3.56)], and FSH level [WMD = −3.46, 95% CI (−7.2, 0.28)] after treatment between Kuntai versus HRT group (P > 0.05). However, Compared with HRT, Kuntai capsule could significantly reduce the total incidence of adverse events [OR = 0.28, 95% CI (0.17, 0.45)].ConclusionsKuntai capsule may be effective for treating menopausal syndrome and lower risk of side effects. The studies we analyzed were of low methodological quality. Therefore, more strictly designed large-scale randomized clinical trials are needed to evaluate the efficacy of Kuntai capsule in menopausal syndrome.     

Associations between genetic polymorphisms of paraoxonase genes and coronary artery disease in a Taiwanese population

ObjectiveWe evaluated the relationship between polymorphisms of the paraoxonase (PON) gene and the risk of coronary artery disease (CAD) in Taiwanese patients.MethodsOur sample set included 369 volunteers, classified into two groups: 162 healthy volunteers and 207 CAD patients aged 60.0 ± 9.7 and 64.3 ± 12.3 years, respectively. Polymorphisms of the PON1 and PON2 genes were determined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) techniques.ResultsThe results indicate that for the PON1 gene, the homozygous genotype RR was found significantly more often among the CAD group compared with the healthy group (OR = 1.965, 95% CI = 1.223–3.159, p = 0.005). Furthermore, for the PON2 gene, the homozygous genotype CC was found significantly more often among the CAD group compared with the control group (OR = 2.525, 95% CI = 1.103–5.780, p = 0.026).ConclusionsIndividuals homozygous for the R allele of the PON1 gene and the C allele of the PON2 gene are more likely to have an increased risk of CAD.     

Knowledge and attitudes regarding clinical trials and willingness to participate among prostate cancer patients

BackgroundEnrollment of minorities in clinical trials remains low. Through a California population-based study of men with early stage prostate cancer, we examined the relationships between race/ethnicity and 1) attitudes, 2) knowledge and 3) willingness to participate in clinical trials.MethodsFrom November 2011–November 2012, we identified all incident cases of prostate cancer in African American, Latino, and Asian American men ages 18–75 years, and a random sample of white men diagnosed in 2008, through the California Cancer Registry, living within 60 miles of a site offering ≥ 1 clinical trial. Participants completed a 30-min telephone interview in English, Spanish, or Chinese. In this cross-sectional population-based study, multivariable logistic regression was used to estimate associations between race/ethnicity and 1) attitudes, 2) knowledge and 3) willingness to participate.ResultsOf 855 participants, 52% were ≥ 65 years, 42% were white, 24% Latino, 19% African American and 15% Asian American. The majority (81%) had medium-to-high health literacy. Compared to non-Latino white men, African American men were less likely to have above average knowledge of clinical trials (OR = 0.55; CI = 0.35–0.86), as were Asian American (OR = 0.55; CI = 0.33–0.93) and Latino men (OR = 0.30; CI = 0.18–0.48). There were no racial/ethnic differences in willingness to participate. The attitude that “researchers are the main beneficiaries” was negatively associated with willingness (OR = 0.63; CI = 0.43–0.93); the attitude that “patients are the main beneficiaries” was positively associated with willingness to participate (OR = 1.57; CI = 1.07–2.29).ConclusionsMen with early stage prostate cancer are willing to take part in clinical trials and this willingness does not vary by race/ethnicity.     

Association of haplotypes in the IL8 gene with susceptibility to chronic periodontitis in a Brazilian population

BackgroundInterleukin 8 (IL-8) is a chemokine related to the initiation and amplification of acute and chronic inflammatory processes. Polymorphisms in the IL8 gene have been associated with inflammatory diseases. We investigated whether the ? 845(T/C) and ? 738(T/A) single nucleotide polymorphisms (SNPs) in the IL8 gene, as well as the haplotypes they form together with the previously investigated ? 353(A/T), are associated with susceptibility to chronic periodontitis.MethodsDNA was extracted from buccal epithelial cells of 400 Brazilian individuals (control n = 182, periodontitis n = 218). SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Disease associations were analyzed by the χ² test, Exact Fisher test and Clump program. Haplotypes were reconstructed using the expectation-maximization algorithm and differences in haplotype distribution between the groups were analyzed to estimate genetic susceptibility for chronic periodontitis development.ResultsWhen analyzed individually, no SNPs showed different distributions between the control and chronic periodontitis groups. Although, nonsmokers carrying the TTA/CAT (OR = 2.35, 95% CI = 1.03–5.36) and TAT/CTA (OR = 6.05, 95% CI = 1.32–27.7) haplotypes were genetically susceptible to chronic periodontitis. The TTT/TAA haplotype was associated with protection against the development of periodontitis (for nonsmokers OR = 0.22, 95% CI = 0.10–0.46).ConclusionAlthough none of the investigated SNPs in the IL8 gene was individually associated with periodontitis, some haplotypes showed significant association with susceptibility to, or protection against, chronic periodontitis in a Brazilian population.     

Trends and Racial Differences in the Use of Androgen Deprivation Therapy for Metastatic Prostate Cancer

ContextAndrogen deprivation therapy (ADT) is widely used to manage the symptoms of advanced prostate cancer and has been shown to slow the progression of the disease. Previous research investigating racial differences in the use of ADT has reported inconsistent findings.ObjectivesThe purpose of this study was to assess use trends for ADT overall and by type (orchiectomy and luteinizing hormone-releasing hormone [LHRH] agonists) and the factors associated with time to receipt for metastatic prostate cancer.MethodsData from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and Medicare claims database were obtained for 5,273 men, aged 65 years and older and diagnosed with Stage IV prostate cancer during 1991–1999 from seven SEER regions. An accelerated failure time regression model with log-normal distribution was used to examine factors associated with mean time to receipt of ADT.ResultsAfrican-American men were less likely than white men to receive any ADT after diagnosis (P < 0.001). Differences were noted in the time to receipt of ADT, with African-American men having a longer mean time to receipt of orchiectomy (time ratio [TR] = 1.50; 95% confidence interval [CI] = 1.03, 2.17) or LHRH agonist (TR = 1.42; 95% CI = 1.06, 1.89) than white men.ConclusionAfrican-American men with metastatic prostate cancer were significantly less likely to receive ADT and, when treated, had a slightly longer time to receipt than white men, which has implications for patients and physicians involved in the palliative management of metastatic prostate cancer.     

Hypervariability in a minisatellite 3' of the apolipoprotein B gene: Allelic distribution and influence on lipid profiles in Han Children from central China

BackgroundApolipoprotein B (apoB) gene 3' variable number tandem repeat (VNTR) is highly variable, and thereby be considered as an informative marker for associative analysis of lipid metabolism.MethodsWe conducted this study to probe the effect of apoB 3' VNTR alleles on lipid profiles in 500 Han children from central China, and to compare the allelic distribution of our subjects with multiple Chinese populations. 14 different alleles of the apoB gene 3' VNTR comprising from HVE22 to HVE44 were identified in our subjects.ResultsAllele size distribution followed unimodal curve with the main peak at HVE35 (58.0%). We detected 37 genotypes in this sampling, the most frequently seen was HVE35/35 with a frequency of 36.4%. M/L carriers had significantly higher total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apoB concentrations than did S/S, M/M or S/M carriers (p < 0.05). Individuals with L allele exhibited significantly higher TC, LDL-C, and apoB levels than those with M or S allele (p < 0.05). The allelic distribution in Central Han Chinese differed from Southern Han Chinese (X² = 41.2, p = 0.00), Zhuang Chinese (X² = 65.4, p = 0.00), and Uighur Chinese (X² = 45.6, p = 0.00). No significant differences in allelic frequencies were observed for apoB 3' VNTR in Central Han Chinese as compared to Northern Han Chinese (X² = 2.5, p = 0.29).ConclusionThis study identified the higher repeat alleles as potential risk factor for dyslipidemia in Han children from Central China. Although five Chinese populations demonstrated uniformly unimodal distributions of allelic frequencies with the main peaks at HVE32–HVE37, there was obvious heterogeneity among these populations.     

Serum neural precursor cell-expressed,developmentally down regulated 9 (NEDD9) level may have a prognostic role in patients with gastric cancer

BackgroundNeural precursor cell-expressed, developmentally down regulated 9 (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved in cancer cell adhesion, migration and invasion. The prognostic value of NEDD9 has been evaluated before and its expression is a predictor of poor prognosis in cancer patients. The objective of this study was to determine the clinical significance of the serum levels of NEDD9 in gastric cancer (GC) patients.Patients and methodsA total of 68 patients with a pathologically confirmed diagnosis of GC were enrolled into this study. Serum NEDD9 concentrations were determined by the solid-phase sandwich (ELISA) method. Twenty-eight healthy age- and sex-matched controls were included into the analysis.ResultsThe median age at diagnosis was 60 years, range 21 to 84 years. Forty-nine (72%) patients were male and cardia was the most common tumor localization (n = 37, 77%) in GC patients. The most frequent histologic subtype was adenocarcinoma (n = 45, 66%). Liver was the most common metastatic site in 32 patients with metastasis (n = 14, 44%). Sixty-one percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx-responsive. The median follow-up time was 8 months (range 1 to 23 months). At the end of the observation period, 17 patients (25%) experienced disease progression and 28 of the remaining patients (41%) died. Median progression-free survival (PFS) and overall survival (OS) of the whole group were 4.0 ± 0.7 months [95% confidence interval (CI) = 3–5 months] and 14.6 ± 1.2 months (95% CI = 12–17 months), respectively. One-year and 2-year OS rates were 54.4% (95% CI = 41.3–67.5) and 51.2% (95% CI = 37.3–65.1), respectively. The median serum NEDD9 levels of GC patients were significantly higher than controls (1339.51 vs. 1187.91 pg/mL, P = 0.02). There was no significant difference according to known disease-related clinicopathological or laboratory parameters (P > 0.05). Serum NEDD9 levels had a significant impact on PFS (P = 0.04). On the other hand, serum NEDD9 levels showed no significantly adverse effect on OS (P = 0.50).ConclusionSerum NEDD9 level may be a diagnostic marker for GC patients. Moreover, our study results showed that it was elevated in GC patients and had an unfavorable prognostic effect. However, it has no predictive role on CTx response.