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.     

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.     

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.     

Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer

BackgroundGlutathione peroxidase 3 (GPX3) can enhance an antioxidant's capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer.MethodsWe first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs.ResultsAmong five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls, 3 SNPs were significant: intronic SNP rs3805435 (OR = 0.70, P = 0.037), intronic SNP 3828599 (OR = 0.68, P = 0.025), and 3′ UTR SNP rs2070593 (OR = 0.48, P = 0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D′ = 0.91).ConclusionsThe reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P = 0.004), whereas the 3′UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk.     

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.     

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.     

A miR-29c binding site genetic variant in the 3′-untranslated region of LAMTOR3 gene is associated with gastric cancer risk

Single nucleotide polymorphisms (SNPs) in the 3′-untranslated regions (UTRs) targeted by putative mircoRNAs (miRNAs) could influence the susceptibility of cancer. Recently, miR-29c has been reported to be down-regulated in gastric cancer (GC) and serve as a tumor suppressor that regulated tumor progression. The present study was aimed at investigating whether the miR-29c binding site SNPs within the 3′-UTRs of target genes affected the gastric cancer risk. Using bioinformatics tools, we chose three SNPs (IGHMBP2 rs3750980, LAMTOR3 rs11944405 and WWOX rs2288035) located in miR-29c binding sites. We genotyped these three SNPs to assess their associations with GC risk in a case-control study comprising 753 GC cases and 950 controls. Among these three SNPs, we found a significantly decreased risk of GC associated with the LAMTOR3 rs11944405 T > C polymorphism [TC vs. TT, adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63–0.99; TC/CC vs. TT, adjusted OR = 0.81, 95% CI = 0.65–1.00]. The significant association was also presented in the subgroup analysis by age (≤ 65), sex (female), depth of invasion (T3/T4), lymph node metastasis (N1-3), distant metastasis (M0) and TNM stage (III/IV). However, no significant association was detected for IGHMBP2 rs3750980 and WWOX rs2288035. Our results suggested that the LAMTOR3 rs11944405 polymorphism may be a potential biomarker for genetic susceptibility to GC.     

Implication of CLU gene polymorphisms in Chinese patients with Alzheimer's disease

BackgroundClusterin (also called apolipoprotein J) has a potential central role in the pathogenesis of Alzheimer's disease (AD). Recently, two genome-wide association studies have identified three variants in CLU gene encoding clusterin associated with AD risk in Caucasians, while there are no studies on the association of CLU with AD risk in Asians.MethodsThe study investigated 324 sporadic late-onset AD (LOAD) and 388 healthy controls matched for sex and age in a Han Chinese population. Three common genetic variants (rs2279590, rs11136000 and rs9331888) in CLU gene were genotyped using MALDI-TOF mass spectrometry.ResultsThe minor allele (G) of the rs9331888 polymorphism within CLU was significantly associated with an increased risk of LOAD (OR = 1.39, 95% CI = 1.13–1.72, P = 0.002). Logistic regression analysis revealed that the rs9331888 polymorphism presented strong associations with LOAD in the dominant, recessive and additive models. No significant differences in genotype and allele frequencies of the rs2279590 and rs11136000 polymorphisms were found between LOAD patients and controls. Haplotype analysis identified a risk haplotype (CCG) (OR = 1.66) and a protective haplotype (CCC)(OR = 0.70).ConclusionsOur findings implicate CLU as a susceptibility gene for LOAD in Han Chinese.     

HER2 codon 655 polymorphism is associated with advanced uterine cervical carcinoma

Objectives:It has been suggested that overexpression of HER2 in advanced cervical tumors can be considered an independent predictor of poor patient outcome.Design and methods:Employing PCR-RFLPs, we examined the distribution of HER2 Ile655Val (rs 1136201) genotypes and alleles in patients with advanced cervical cancer (n = 109) and controls (n = 220).Results:Odds ratio (OR) for patients with advanced cervical cancer with the HER2 Val/Val homozygous or Val/Ile heterozygous state was 1.778 (95% CI = 1.117–2.830, p = 0.0176). We also observed an association of the HER2 Val/Val genotype with advanced cervical cancer in the patient group OR = 3.706 (95% CI = 1.061–12.950, p = 0.0459). However, we did not find a significant association between the distribution of genotypes or alleles and cancer characteristics for the HER2 Ile655Val polymorphism.Conclusions:Our results indicate that the HER2 655Val variant may be associated with the incidence of advanced cervical cancer.     

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.     

The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta-analysis of 1938 cases and 1990 controls

ObjectivesGenetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD.Design and methodsTwo investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0.Results5 case–control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR = 0.595, 95%CI = 0.298–1.188, P = 0.141; G/G vs G/A + A/A: OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G/G + G/A vs A/A: OR = 0.611, 95%CI = 0.334–1.119, P = 0.111; OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G vs A: OR = 0.843, 95%CI = 0.675–1.053, P = 0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P = 0.008, P = 0.021, P = 0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity.ConclusionsOur meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.     

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 the MS4A2 gene promoter C-109T or the 7th exon E237G polymorphisms with asthma risk: A meta-analysis

Background and objectiveA large number of studies have examined the association between the Membrane-spanning 4 domains, superfamily A, number 2 (MS4A2) gene C-109T (rs1441586) or E237G (rs569108) variants and asthma risk. However, the results are inconsistent and inconclusive. To derive a more precise estimation, a meta-analysis was performed.MethodsMeta-analyses were conducted with the data from case–control association studies (24 studies with 4496 asthmatics and 4571 controls for E237G variant and 9 studies including 2005 cases and 1868 control for C-109T polymorphisms, respectively). Random-effects model was used to calculate summary odds ratios (ORs).ResultsFor the MS4A2 gene E237G variant, no significant associations with asthma were found in overall population; we observed an elevated risk of atopic asthma among subjects with the 237G allele (OR = 1.341, 95% CI: 1.039–1.732 for G versus E and OR = 1.374, 95% CI: 1.032–1.828 for EG + GG versus EE) in the stratified meta-analysis. As for the MS4A2 gene C-109T polymorphism, no significant associations with asthma risk were observed in the total population; in subgroup analysis by ethnicity of subjects we found increased asthma risk among Asians carrying T allele (OR = 1.140, 95% CI: 1.019–1.276 for T versus C and OR = 1.359, 95% CI: 1.029–1.794 for TT versus CC).ConclusionsData indicated that the MS4A2 gene E237G variant may be a risk factor for developing atopic asthma and the promoter -109T allele is a potential risk factor of asthma in Asians.     

Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

ObjectivesMatrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population.Design and methodsStudy enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms ? 1607 1G/2G, ? 519 A/G and ? 340 T/C were genotyped by PCR and RFLP methods.ResultsIndividuals carrying MMP-1 ? 1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR = 1; OR = 1.87 95% CI 1.29–2.07; OR = 3.49 95% CI 1.67–7.30, p = 0.0009, respectively). Compared to the referent haplotype 2G_? 1607-T_? 340-A_? 519, the haplotypes 1G_? 1607-T_? 340-A_? 519, 1G_? 1607-T_? 340-G_? 519 and 2G_? 1607-C_? 340-A_? 519 had statistically significant protective effect on CP presence (OR = 0.41, 95% CI 0.29–0.81, p = 0.01; OR = 0.56, 95% CI 0.44–0.89, p = 0.01; OR = 0.43, 95% CI 0.27–0.86, p = 0.02, respectively).ConclusionsMMP-1 ? 1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.     

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.     

The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese diffuse large B cell lymphoma patients

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR = 1.48, 95% CI: 1.08–2.02, Pc = 0.03; GT: OR = 1.96, 95% CI: 1.25–3.07, Pc < 0.01), while genotype AT in this locus seemed to be protective (OR = 0.29, 95% CI: 0.02–0.72, Pc = 0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR = 2.38, 95% CI: 1.52–3.74, Pc < 0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR = 5.21, 95% CI: 2.58–10.54, Pc < 0.01); haplotype of G-T in 2677–3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR = 3.97, 95% CI: 2.31–6.85, Pc < 0.01; 2677GT/3435TT: OR = 4.55, 95% CI: 2.02–10.22, Pc < 0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677–3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.     

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.     

Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men

BackgroundSingle nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men.MethodSerum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged ≥ 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using T_m-shift allele-specific PCR.ResultsSNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p < 0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p = 0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p = 0.019 and p = 1 × 10^? 5, respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p = 1 × 10^? 5).ConclusionThe genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.