Faculty Bibliography

BACKGROUND: Polycyclic aromatic hydrocarbons (PAH) are produced by the burning and processing of fuel oils, and have been associated with oxidant stress, insulin resistance and hypertension in adults. Few studies have examined whether adolescents are susceptible to cardiovascular effects of PAHs. OBJECTIVE: To study associations of PAH exposure with blood pressure (BP) and brachial artery distensibility (BAD), an early marker of arterial wall stiffness, in young boys attending three schools in Jeddah, Saudi Arabia in varying proximity to an oil refinery. METHODS: Air samples collected from the three schools were analyzed for PAHs. PAH metabolites (total hydroxyphenanthrenes and 1-hydroxypyrene) were measured in urine samples from 184 adolescent males, in whom anthropometrics, heart rate, pulse pressure, brachial artery distensibility and blood pressure were measured. Descriptive, bivariate and multivariable analyses were performed to assess relationships of school location and urinary PAH metabolites with cardiovascular measures. RESULTS: Total suspended matter was significantly higher (444+/-143mug/m(3)) at the school near the refinery compared to a school located near a ring road (395+/-65mug/m(3)) and a school located away from vehicle traffic (232+/-137mug/m(3)), as were PAHs. Systolic (0.47 SD units, p=0.006) and diastolic (0.53 SD units, p<0.001) BP Z-scores were highest at the school near the refinery, with a 4.36-fold increase in prehypertension (p=0.001), controlling for confounders. No differences in pulse pressure, BAD and heart rate were noted in relationship to school location. Urinary total hydroxyphenanthrenes and 1-hydroxypyrene were not associated with cardiovascular outcomes. CONCLUSIONS: Proximity to an oil refinery in Saudi Arabia is associated with prehypertension and increases in PAH and particulate matter exposures. Further study including insulin resistance measurements, better control for confounding, and longitudinal measurement is indicated.

Substance abuse represents one of the most common diagnoses in jail settings and features prominently in the path into criminal justice involvement. In addition, substance abuse plays a major role in mortality, morbidity, and recidivism after release from jail. In 2008, a substance abuse treatment program was begun within the New York City jail system, the nation's second largest. This program, A Road Not Taken (ARNT), works collaboratively with courts, security officials within the jail, and community programs to identify inmates who have substance abuse concerns and provide in-jail programming and coordination of treatment after jail. An evaluation of ARNT participants revealed that they experienced a lower rate in incarceration after their program participation than they did before participation.

Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

[This corrects the article DOI: 10.1371/journal.pone.0117574.].

Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH)D concentration in GWAS were also associated with plasma 25(OH)D in our study (p-trend <0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH)D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.

Background: A subset of high grade serous carcinomas may arise from the fallopian tube, while some endometrioid and clear cell carcinomas may derive from endometrial tissue. Previous studies have suggested differences in ovarian cancer risk factors by histologic subtypes, but had limited sample sizes. In the Ovarian Cancer Cohort Consortium (OC3), we evaluated associations of reproductive, hormonal, demographic and lifestyle factors, and family history of cancer with ovarian cancer subtypes. Identification of potential differences in associations among subtypes is important for clarifying ovarian cancer etiology and for developing novel prevention and risk prediction approaches. Methods: Among over 1.2 million women from 21 cohort studies, 4,347 ovarian cancers with histology information were identified during follow-up (3223 serous, 555 endometrioid, 316 mucinous, 253 clear cell). We used competing risks Cox proportional hazards regression to compute risk factor associations by histologic subtype. Models were stratified on study and year of birth and adjusted for age, parity and oral contraceptive use; subtype heterogeneity was evaluated by a likelihood ratio test. Unsupervised hierarchical clustering was used to evaluate patterns of risk factors by histology. Results: Most risk factors showed significant heterogeneity across histologic subtypes. Higher parity was most strongly associated with lower risks of endometrioid (RR per child: 0.79; 95%CI: 0.74-0.85) and clear cell (RR: 0.69; 95%CI: 0.61-0.78) carcinomas (p-het<0.0001). Age at menopause was positively and tubal ligation was inversely associated only with endometrioid and clear cell carcinomas (p-het = 0.02 and 0.003, respectively). Long-term menopausal hormone use (>5 years) was associated with endometrioid carcinomas (RR: 2.23; 95% CI: 1.46-3.42) and serous carcinomas (RR: 1.66; 95% CI: 1.44-1.92), and inversely associated with clear cell carcinomas (RR: 0.43; 95% CI: 0.20-0.91; p-het = 0.001). Family history of breast cancer was associated with increased risk of serous carcinomas (RR:1.13; 95% CI:1.02-1.27) and endometrioid carcinomas (RR: 1.44; 95% CI: 1.12-1.87; p-het = 0.02). Smoking (per 20 pack years) showed a positive association with mucinous carcinomas (RR: 1.38; 95% CI: 1.09-1.75) and an inverse association with clear cell carcinomas (RR:0.62; 95% CI: 0.46-0.85; p-het = 0.001). In unsupervised hierarchical clustering, serous and mucinous carcinomas clustered in one group and endometrioid and clear cell carcinomas in the other. Conclusion: Our results demonstrate heterogeneous associations of risk factors with ovarian cancer subtypes, supporting the hypothesis that the subtypes develop through different pathways. Most established risk factors were more strongly associated with non-serous carcinomas, suggesting that risk prediction may be more challenging for serous cancers, the most fatal subtype

The global economic downturn has been associated with increased unemployment in many countries. Insights into the impact of unemployment on specific health conditions remain limited. We determined the association between unemployment and prostate cancer mortality in members of the Organisation for Economic Co-operation and Development (OECD). We used multivariate regression analysis to assess the association between changes in unemployment and prostate cancer mortality in OECD member states between 1990 and 2009. Country-specific differences in healthcare infrastructure, population structure, and population size were controlled for and lag analyses conducted. Several robustness checks were also performed. Time trend analyses were used to predict the number of excess deaths from prostate cancer following the 2008 global recession. Between 1990 and 2009, a 1% rise in unemployment was associated with an increase in prostate cancer mortality. Lag analysis showed a continued increase in mortality years after unemployment rises. The association between unemployment and prostate cancer mortality remained significant in robustness checks with 46 controls. Eight of the 21 OECD countries for which a time trend analysis was conducted, exhibited an estimated excess of prostate cancer deaths in at least one of 2008, 2009, or 2010, based on 2000-2007 trends. Rises in unemployment are associated with significant increases in prostate cancer mortality. Initiatives that bolster employment may help to minimise prostate cancer mortality during times of economic hardship.

Several studies have investigated associations between socioeconomic status (SES) and indicators of children's physiological and cognitive self-regulation. Although objective measures of family SES may be good proxies for families' experiences of disadvantage, less is known about subjective aspects of families' experiences. We hypothesize that subjective social status (SSS) and perceived stress may be important independent predictors of children's stress physiology and executive functioning (EF). Eighty-two children from diverse SES backgrounds were administered EF measures and provided saliva samples for cortisol assay. Caregivers reported on objective SES, SSS, and perceived stress. Results suggest that SES and SSS are both independently and positively related to EF. In models predicting stress physiology, higher perceived stress was associated with lower baseline cortisol. Moreover, SES and age interacted to predict cortisol levels such that among younger children, lower SES was associated with higher cortisol, whereas among older children, lower SES was associated with lower cortisol. Results highlight the importance of considering both objective and subjective indicators of families' SES and stressful experiences in relation to multiple aspects of children's self-regulation.