Association between polycyclic aromatic hydrocarbon exposure and hypertension among the U.S. adults in the NHANES 2003-2016: A cross-sectional study.

The global burden of hypertension, the major cause of cardiovascular disease (CVD) globally, remains unresolved. Exposure to PM2.5 has been linked to hypertension (HTN) in adults and the elderly globally according to previous studies. Nonetheless, evidence on the association of polycyclic aromatic hydrocarbon (PAH) exposure and HTN risk in the general adult population in the United States was limited. To investigate the relationship between PAH exposure and HTN in adults in the United States, cross-sectional data during 2003 and 2016 from the National Health and Nutrition Examination Survey (NHANES) on a stratified multistage random sample of the civilian non-institutionalized population were utilized. After eliminating individuals with incomplete information of interest, the final analysis contained 8951 subjects aged ≥20. In the multivariate logistic regression model, 1-hydroxynaphthalene and 2-hydroxyfluorene were found positively associated with increased risk of HTN among overall participants after adjusting for the covariates. 1-hydroxynaphthalene and 2-hydroxynaphthalene showed positive associations with HTN risk among overweight participants. In the Bayesian kernel machine regression (BKMR) model, 1-hydroxynaphthalene and 2-hydroxyfluorene presented great importance to HTN risk among overall individuals. In the male subgroup analyses by BKMR, 2-hydroxyfluorene presented a positive effect on HTN risk when the remaining OH-PAHs were set at their 25th, 50th, and 75th percentile. Our findings highlight the complexities of estimating the risk of HTN associated with mixed PAH exposure, and additional longitudinal studies are required to determine the exact link between PAH exposure and HTN risk, as well as the underlying mechanisms.

Urine 2-hydroxyphenanthrene is associated with current asthma: evidence from NHANES 2007-2012.

OBJECTIVE: The current study aims to explore the effects of nine urine monohydroxy PAH metabolites (OHPAH) including 1-hydroxynaphthalene (1-OHNAP), 2-hydroxynaphthalene (2-OHNAP), 3-hydroxyfluorene (3-OHFLU), 9-hydroxyfluorene (9-OHFLU), 1-hydroxyphenanthrene (1-OHPHE), 2-hydroxyphenanthrene (2-OHPHE), 3-hydroxyphenanthrene (3-OHPHE), and 1-hydroxypyrene (1-OHPYR) on current asthma in people in the United States using a variety of statistical techniques. METHODS: A cross-sectional examination of a subsample of 3804 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) was conducted between 2007 and 2012. To investigate the relationship between urine OHPAHs levels and current asthma, multivariate logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) were utilized. RESULTS: In the multivariate logistic regression model, after controlling for confounders, urine 2-OHPHE was associated with current asthma in both male (AOR = 7.17, 95% CI: 1.28-40.08) and female (AOR = 2.91, 95% CI: 1.06-8.01) smokers. In the qgcomp analysis, 2-OHPHE (39.5%), 1-OHNAP (33.1%), and 2-OHNAP (22.5%) were the major positive contributors to the risk of current asthma (OR = 2.29, 95% CI: 0.99, 5.25), and in female smokers, 9-OHFLU (25.8%), 2-OHFLU (21.5%), and 2-OHPHE (15.1%) were the major positive contributors (OR = 2.19, 95% CI: 1.06, 4.47). The results of the BKMR model basically agreed with qgcomp analysis. CONCLUSION: Our results demonstrate a strong association of urine 2-OHPHE with current asthma, and further longitudinal studies are needed to understand the precise relationship between PAH exposure and current asthma risk.

Association between food insecurity and access to a mental health professional: cross-sectional analysis of NHANES 2007-2014.

BACKGROUND: To determine if individuals with food insecurity (FI) were less likely to have seen a mental health professional (MHP) within the past year than individuals without FI. METHODS: This is a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States between 2007 and 2014. All participants 20 years of age or older were eligible for this study. We excluded participants who were pregnant, missing FI data, or missing data from the Patient Health Questionnaire (PHQ-9). The primary outcome was self-reported contact with a MHP in the past 12 months. We used multivariable logistic regression models to test the association between FI and contact with a MHP, controlling for all demographic and clinical covariates. RESULTS: Of the 19,789 participants, 13.9% were food insecure and 8.1% had major depressive disorder (MDD). In bivariate analysis, participants with FI were significantly more likely to have MDD (5.3% vs 2.8%, p < 0.0001) and to have been seen by a MHP in the preceding 12 months (14.0% vs 6.9%, p < 0.0001). In multivariable models, adults with FI had higher odds of having seen a MHP (OR = 1.32, CI: 1.07, 1.64). CONCLUSIONS: This study demonstrates that individuals with FI were significantly more likely to have seen a MHP in the preceding 12 months compared to individuals without FI. Given the growing interest in addressing unmet social needs in healthcare settings, this data suggests that visits with MHPs may be a valuable opportunity to screen for and intervene on FI.

Breastfeeding and Atopic Dermatitis Risk: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

OBJECTIVES: The effect of breastfeeding on atopic dermatitis (AD) remains controversial. To determine the association -between breastfeeding and AD, we conducted an updated meta-analysis of prospective cohort studies. METHODS: A comprehensive search of PubMed, EMBASE, MEDLINE and Cochrane Library was conducted. Studies meeting the predetermined criteria were evaluated by 2 authors independently. The pooled relative risk (RR) adjusted for confounders with its 95% CI was calculated by a random-effects model. Heterogeneity was explored by subgroup analysis and meta-regression. RESULTS: A total of 27 studies were included for meta-analysis. The pooled estimates for the effect of total and exclusive breastfeeding on AD were 1.01 (95% CI 0.93-1.10) and 0.99 (95% CI 0.88-1.11), respectively. Heterogeneity was substantial across studies (total: p < 0.01 or I2 = 65.2%; exclusive: p < 0.01 or I2 = 72.3%). There was a weak evidence for a protective effect of breastfeeding against AD in cohorts with atopic heredity (total: RR 0.85, 95% CI 0.74-0.98; exclusive: RR 0.83, 95% CI 0.70-0.97). In cohorts without atopic heredity, the effect shifted to the risk side when limited to exclusive breastfeeding (RR 1.19, 95% CI 1.02-1.40) while it dropped towards null when limited to total breastfeeding (RR 1.11, 95% CI 0.94-1.31). CONCLUSIONS: There is no association between AD and breastfeeding, regardless of total or exclusive breastfeeding patterns. There is some evidence for a protective function of exclusive and total breastfeeding in a cohort with atopic heredity. The effect shifts to the risk side in cohorts without atopic heredity. However, these findings should be interpreted with caution because heterogeneity is evident.

Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes.

BACKGROUND: Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis. RESULTS: Single nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10-7. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = -1.14 (0.20); p-value = 9.1 × 10-9). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8). CONCLUSIONS: Genetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.

Development of a video-simulation instrument for assessing cognition in older adults.

BACKGROUND: Commonly used methods to assess cognition, such as direct observation, self-report, or neuropsychological testing, have significant limitations. Therefore, a novel tablet computer-based video simulation was created with the goal of being valid, reliable, and easy to administer. The design and implementation of the SIMBAC (Simulation-Based Assessment of Cognition) instrument is described in detail, as well as informatics "lessons learned" during development. RESULTS: The software emulates 5 common instrumental activities of daily living (IADLs) and scores participants' performance. The modules were chosen by a panel of geriatricians based on relevance to daily functioning and ability to be modeled electronically, and included facial recognition, pairing faces with the correct names, filling a pillbox, using an automated teller machine (ATM), and automatic renewal of a prescription using a telephone. Software development included three phases 1) a period of initial design and testing (alpha version), 2) pilot study with 10 cognitively normal and 10 cognitively impaired adults over the age of 60 (beta version), and 3) larger validation study with 162 older adults of mixed cognitive status (release version). Results of the pilot study are discussed in the context of refining the instrument; full results of the validation study are reported in a separate article. In both studies, SIMBAC reliably differentiated controls from persons with cognitive impairment, and performance was highly correlated with Mini Mental Status Examination (MMSE) score. Several informatics challenges emerged during software development, which are broadly relevant to the design and use of electronic assessment tools. Solutions to these issues, such as protection of subject privacy and safeguarding against data loss, are discussed in depth. Collection of fine-grained data (highly detailed information such as time spent reading directions and the number of taps on screen) is also considered. CONCLUSIONS: SIMBAC provides clinicians direct insight into whether subjects can successfully perform selected cognitively intensive activities essential for independent living and advances the field of cognitive assessment. Insight gained from the development process could inform other researchers who seek to develop software tools in health care.

APOL1 associations with nephropathy, atherosclerosis, and all-cause mortality in African Americans with type 2 diabetes.

Albuminuria and reduced estimated glomerular filtration rate (eGFR) associate with two apolipoprotein L1 gene (APOL1) variants in nondiabetic African Americans (AAs). Whether APOL1 associates with subclinical atherosclerosis and survival remains unclear. To determine this, 717 African American-Diabetes Heart Study participants underwent computed tomography to determine coronary artery-, carotid artery-, and aorta-calcified atherosclerotic plaque mass scores in addition to the urine albumin:creatinine ratio (UACR), eGFR, and C-reactive protein (CRP). Associations between mass scores and APOL1 were assessed adjusting for age, gender, African ancestry, body mass index (BMI), hemoglobin A1c, smoking, hypertension, use of statins and angiotensin-converting enzyme inhibitors, albuminuria, and eGFR. Participants were 58.9% female with mean age 56.5 years, eGFR 89.5 ml/min per 1.73 m(2), UACR 169.6 mg/g, and coronary artery-, carotid artery-, and aorta-calcified plaque mass scores of 610, 171, and 5378, respectively. In fully adjusted models, APOL1 risk variants were significantly associated with lower levels of carotid artery-calcified plaque (ß=-0.42, s.e. 0.18; dominant model) and marginally lower coronary artery plaque (ß=-0.36, s.e. 0.21; dominant model), but not with aorta-calcified plaque, CRP, UACR, or eGFR. By the end of a mean follow-up of 5.0 years, 89 participants had died. APOL1 nephropathy risk variants were significantly associated with improved survival (hazard ratio 0.67 for one copy; 0.44 for two copies). Thus, APOL1 nephropathy variants associate with lower levels of subclinical atherosclerosis and reduced risk of death in AAs with type 2 diabetes mellitus.

Re-Sequencing of the APOL1-APOL4 and MYH9 Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression.

BACKGROUND: In African Americans (AAs), APOL1 G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the APOL1 loci, since earlier age ESKD is observed in some AAs with one APOL1 renal-risk variant, and because the adjacent gene MYH9 is associated with nephropathy in populations lacking G1 and G2 variants. METHODS: Re-sequencing was performed across a ∼275 kb region encompassing the APOL1-APOL4 and MYH9 genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single APOL1 G1 or G2 risk variant. RESULTS: Sequencing identified 3,246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions. No new coding variations were identified. Eleven variants, including a rare APOL3 Gln58Ter null variant (rs11089781), were genotyped in a replication panel of 1,571 AA ESKD cases and 1,334 controls. After adjusting for APOL1 G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with <2 APOL1 G1 and/or G2 alleles (849 cases; 1,139 controls), the APOL3 null variant was nominally associated with ESKD (recessive model, OR 1.81; p = 0.026); however, analysis in 807 AA cases and 634 controls from the Family Investigation of Nephropathy and Diabetes did not replicate this association. CONCLUSION: Additional common variants in the APOL1-APOL4-MYH9 region do not contribute significantly to ESKD risk beyond the APOL1 G1 and G2 alleles.

Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease.

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.

Gene-gene interactions in APOL1-associated nephropathy.

BACKGROUND: Two APOL1 nephropathy variants confer substantial risk for non-diabetic end-stage kidney disease (ESKD) in African Americans (AAs). Since not all genetically high-risk individuals develop ESKD, modifying factors likely contribute. Forty-two potentially interactive single nucleotide polymorphisms (SNPs) from a genome-wide association study in non-diabetic ESKD were tested for interaction with APOL1 to identify genes modifying risk for non-diabetic nephropathy. METHODS: SNPs were examined in an expanded sample of 1367 AA non-diabetic ESKD cases and 1504 AA non-nephropathy controls, with validation in an independent family-based cohort containing 608 first-degree relatives of index cases with non-diabetic ESKD. Logistic regression and mixed models were fitted to test for interaction effects with APOL1 on ESKD, estimated kidney function and albuminuria. RESULTS: Among ESKD samples, 14 of 42 SNPs demonstrated suggestive APOL1 interaction with P-values <0.05. After Bonferroni correction, significant interactions with APOL1 were seen with SNPs in podocin (rs16854341; NPHS2, P = 8.0 × 10(-4)), in SDCCAG8 (rs2802723; P = 5.0 × 10(-4)) and near BMP4 (rs8014363; P = 1.0 × 10(-3)); with trends for ENOX1 (rs9533534; P = 2.2 × 10(-3)) and near TRIB1 (rs4457349; P = 5.7 × 10(-3)). The minor allele in NPHS2 markedly changed the APOL1-ESKD association odds ratio (OR) from 7.03 to 1.76 (∼50% reduction in effect per copy of the minor allele), rs2802723 changed the OR from 5.1 to 10.5, and rs8014363 increased the OR from 4.8 to 9.5. NPHS2 (P = 0.05) and SDCCAG8 (P = 0.03) SNPs demonstrated APOL1 interaction with albuminuria in independent family-based samples. CONCLUSIONS: Variants in NPHS2, SDCCAG8 and near BMP4 appear to interact with APOL1 to modulate the risk for non-diabetic ESKD in AAs.

Differential effects of MYH9 and APOL1 risk variants on FRMD3 Association with Diabetic ESRD in African Americans.

Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed using the Affymetrix SNP Array 6.0 in 966 AA with T2DN and 1,032 non-diabetic, non-nephropathy (NDNN) controls, with and without adjustment for c22 nephropathy risk variants. No associations were seen between FRMD3 SNPs and T2DN before adjusting for c22 variants. However, logistic regression analysis revealed seven FRMD3 SNPs significantly interacting with MYH9-a finding replicated in 640 additional AA T2DN cases and 683 NDNN controls. Contrasting all 1,592 T2DN cases with all 1,671 NDNN controls, FRMD3 SNPs appeared to interact with the MYH9 E1 haplotype (e.g., rs942280 interaction p-value = 9.3E⁻7 additive; odds ratio [OR] 0.67). FRMD3 alleles were associated with increased risk of T2DN only in subjects lacking two MYH9 E1 risk haplotypes (rs942280 OR = 1.28), not in MYH9 E1 risk allele homozygotes (rs942280 OR = 0.80; homogeneity p-value = 4.3E⁻4). Effects were weaker stratifying on APOL1. FRMD3 SNPS were associated with T2DN, not type 2 diabetes per se, comparing AAs with T2DN to those with diabetes lacking nephropathy. T2DN-associated FRMD3 SNPs were detectable in AAs only after accounting for MYH9, with differential effects for APOL1. These analyses reveal a role for FRMD3 in AA T2DN susceptibility and accounting for c22 nephropathy risk variants can assist in detecting DN susceptibility genes.

Relationship Between Family History and Quality of Life in Patients with Psoriasis: A Cross-Sectional Study from China.

Purpose: The purpose of this study was to investigate the comprehensive impact of family history of psoriasis, lesion size, disease severity, and the possibility of joint involvement on patients' quality of life(QoL). Patients and Methods: Data from 5961 patients with psoriasis recruited from 440 hospitals throughout China were analyzed. The effects of family history of psoriasis, Body Surface Area(BSA), Psoriasis Area and Severity Index(PASI), and Psoriasis Epidemiology Screening Tool(PEST) on their Dermatology Life Quality Index(DLQI) were studied using a moderated chained mediated effects test. Results: A total of 912 patients (15.30%) had a family history of psoriasis, and 5071 patients (85.10%) had plaque psoriasis. In patients with plaque psoriasis, the variables of family history, PASI, PEST, and DLQI were positively correlated with each other. Additionally, in patients with other types of psoriasis, PASI was positively correlated with PEST and DLQI. Age was positively correlated with PASI and PEST and negatively correlated with DLQI in patients with plaque psoriasis; their Body Mass Index(BMI) and disease duration were in positive correlation with PASI and PEST. The mediation effect of PASI and PEST between family history and DLQI was remarkable in patients with plaque psoriasis and not in those with other types of psoriasis. BSA moderated the association between family history and PASI in patients with plaque psoriasis. Conclusion: PASI and PEST play a chain mediating role in the relationship between family history and DLQI in patients with plaque psoriasis, and high levels of BSA increase the ability of family history to positively predict PASI in plaque psoriasis, thereby affecting the patient's QoL.

Associations of plasma proteomics and age-related outcomes with brain age in a diverse cohort.

Machine learning models are increasingly being used to estimate "brain age" from neuroimaging data. The gap between chronological age and the estimated brain age gap (BAG) is potentially a measure of accelerated and resilient brain aging. Brain age calculated in this fashion has been shown to be associated with mortality, measures of physical function, health, and disease. Here, we estimate the BAG using a voxel-based elastic net regression approach, and then, we investigate its associations with mortality, cognitive status, and measures of health and disease in participants from Atherosclerosis Risk in Communities (ARIC) study who had a brain MRI at visit 5 of the study. Finally, we used the SOMAscan assay containing 4877 proteins to examine the proteomic associations with the MRI-defined BAG. Among N = 1849 participants (age, 76.4 (SD 5.6)), we found that increased values of BAG were strongly associated with increased mortality and increased severity of the cognitive status. Strong associations with mortality persisted when the analyses were performed in cognitively normal participants. In addition, it was strongly associated with BMI, diabetes, measures of physical function, hypertension, prevalent heart disease, and stroke. Finally, we found 33 proteins associated with BAG after a correction for multiple comparisons. The top proteins with positive associations to brain age were growth/differentiation factor 15 (GDF-15), Sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SEVP 1), matrilysin (MMP7), ADAMTS-like protein 2 (ADAMTS), and heat shock 70 kDa protein 1B (HSPA1B) while EGF-receptor (EGFR), mast/stem-cell-growth-factor-receptor (KIT), coagulation-factor-VII, and cGMP-dependent-protein-kinase-1 (PRKG1) were negatively associated to brain age. Several of these proteins were previously associated with dementia in ARIC. These results suggest that circulating proteins implicated in biological aging, cellular senescence, angiogenesis, and coagulation are associated with a neuroimaging measure of brain aging.

Rural-urban disparities in health status among US cancer survivors.

BACKGROUND: Although rural residents are more likely to be diagnosed with more advanced cancers and to die of cancer, little is known about rural-urban disparities in self-reported health among survivors. METHODS: The authors identified adults who had a self-reported history of cancer from the National Health Interview Survey (2006-2010). Rural-urban residence was defined using US Census definitions. Logistic regression with weighting to account for complex sampling was used to assess rural-urban differences in health status after accounting for differences in demographic characteristics. RESULTS: Of the 7804 identified cancer survivors, 20.8% were rural residents. This translated to a population of 2.8 million rural cancer survivors in the United States. Rural survivors were more likely than urban survivors to be non-Hispanic white (P < .001), to have less education (P < .001), and to lack health insurance (P < .001). Rural survivors reported worse health in all domains. After adjustment for sex, race/ethnicity, age, marital status, education, insurance, time since diagnosis, and number of cancers, rural survivors were more likely to report fair/poor health (odds ratio, 1.39; 95% confidence interval, 1.20-1.62), psychological distress (odds ratio, 1.23; 95% confidence interval, 1.00-1.50), ≥2 noncancer comorbidities (odds ratio, 1.15; 95% confidence interval, 1.01-1.32), and health-related unemployment (odds ratio, 1.66; 95% confidence interval, 1.35-2.03). CONCLUSIONS: The current results provide the first estimates of the proportion and number of US adult cancer survivors who reside in rural areas. Rural cancer survivors are at greater risk for a variety of poor health outcomes, even many years after their cancer diagnosis, and should be a target for interventions to improve their health and well being.

HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).

Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate cancer (194 of 382, 51 %) than those without (42 of 137, 30 %), P = 9.9 × 10(-8) [odds ratio 4.42 (95 % confidence interval 2.56-7.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P = 6.5 × 10(-6)). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95 % of carriers, consistent with a founder effect. Clinical characteristics of cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in ~5 % of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer.

Rural-urban differences in health behaviors and implications for health status among US cancer survivors.

PURPOSE: Rural US adults have increased risk of poor outcomes after cancer, including increased cancer mortality. Rural-urban differences in health behaviors have been identified in the general population and may contribute to cancer health disparities, but have not yet been examined among US survivors. We examined rural-urban differences in health behaviors among cancer survivors and associations with self-reported health and health-related unemployment. METHODS: We identified rural (n = 1,642) and urban (n = 6,162) survivors from the cross-sectional National Health Interview Survey (2006-2010) and calculated the prevalence of smoking, physical activity, overweight/obesity, and alcohol consumption. Multivariable models were used to examine the associations of fair/poor health and health-related unemployment with health behaviors and rural-urban residence. RESULTS: The prevalence of fair/poor health (rural 36.7 %, urban 26.6 %), health-related unemployment (rural 18.5 %, urban 10.6 %), smoking (rural 25.3 %, urban 15.8 %), and physical inactivity (rural 50.7 %, urban 38.7 %) was significantly higher in rural survivors (all p < .05); alcohol consumption was lower (rural 46.3 %, urban 58.6 %), and there were no significant differences in overweight/obesity (rural 65.4 %, urban 62.6 %). All health behaviors were significantly associated with fair/poor health and health-related unemployment in both univariate and multivariable models. After adjustment for behaviors, rural survivors remained more likely than urban survivors to report fair/poor health (OR = 1.21, 95 % CI 1.03-1.43) and health-related unemployment (OR = 1.49, 95 % CI 1.18-1.88). CONCLUSIONS: Rural survivors may need tailored, accessible health promotion interventions to address health-compromising behaviors and improve outcomes after cancer.

Racial/Ethnic disparities in health care receipt among male cancer survivors.

OBJECTIVES: We examined racial/ethnic disparities in health care receipt among a nationally representative sample of male cancer survivors. METHODS: We identified men aged 18 years and older from the 2006-2010 National Health Interview Survey who reported a history of cancer. We assessed health care receipt in 4 self-reported measures: primary care visit, specialist visit, flu vaccination, and pneumococcal vaccination. We used hierarchical logistic regression modeling, stratified by age (< 65 years vs ≥ 65 years). RESULTS: In adjusted models, older African American and Hispanic survivors were approximately twice as likely as were non-Hispanic Whites to not see a specialist (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.19, 2.68 and OR = 2.09; 95% CI = 1.18, 3.70, respectively), not receive the flu vaccine (OR = 2.21; 95% CI = 1.45, 3.37 and OR = 2.20; 95% CI = 1.21, 4.01, respectively), and not receive the pneumococcal vaccine (OR = 2.24; 95% CI = 1.54, 3.24 and OR = 3.10; 95% CI = 1.75, 5.51, respectively). CONCLUSIONS: Racial/ethnic disparities in health care receipt are evident among older, but not younger, cancer survivors, despite access to Medicare. These survivors may be less likely to see specialists, including oncologists, and receive basic preventive care.

Photoredox catalysis in alkene and alkyne alkylsulfonylations: the construction of Markovnikov selective α-sulfones.

Photoredox alkene or alkyne alkylsulfonylation has been achieved with phthalimide esters and sulfinates providing unexpected α-sulfones. Mechanistic studies disclose that the preferential alkyl radical addition to the alkene or the Markovnikov hydrosulfonation of the alkyne should contribute to the formation of the ß-alkylated α-sulfones. Moreover, the reaction is easy to operate covering quite large substrate scales including primary, secondary and tertiary alkyl groups and all sorts of terminal aryl alkenes or alkynes. Besides, the reaction was also suitable for the sulfonylation of several drug molecules.

Nickel-Catalyzed 8-Aminoquinoline Directed Reductive Dialkylcyclization/Homodialkylation of Unactivated Alkenes.

Chemo and regioselective dialkylation of alkene is an efficient protocol for constructing useful chemicals, but challenges remain in the unrestricted application of alkylating reagents. Alkyl bromide belongs to the easy-to-access and operable alkyl electrophiles that can be used in reductive coupling with alkenes. Here, we reported convenient strategies for dialkylcyclization and homodialkylation of unactivated ß,γ- and γ,δ-unsaturated alkenyl amides with 1,3-dibromoalkanes or primary alkyl bromides under nickel-catalyzed reductive conditions that exhibited high regioselectivity and functional-group tolerance.

Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG.

BACKGROUND: In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS: In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS: Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS: These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer.