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Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP interaction pairs can predict PCa aggressiveness with a medium to large effect size. For the EA PCa patients, the interaction between rs1801133 (MTHFR) and rs2236225 (MTHFD1), and rs1801131 (MTHFR) and rs7587117 (SLC4A5) were significantly associated with aggressive PCa. For the AA PCa patients, the interaction of DHFR-19bp polymorphism and rs4652 (LGALS3) was significantly associated with aggressive PCa. Conclusions: These SNP–SNP interactions in the folate metabolism-related genes have a larger impact than SNP individual effects on tumor aggressiveness for EA and AA PCa patients. These findings can provide valuable information for potential biological mechanisms of PCa aggressiveness.

Environmental and occupational agents are causes of cancer and disease worldwide while their control and the reduction of the associated disease burden remains complex.This paper summarizes the current status of the burden of environmental and occupational causes of disease in the Americas based on presentations from a panel on environment, occupation and other environmental risk factors for cancer in the Americas, delivered in Panama, at the international conference Promoting Health Equity and Transnational Collaborations for the Prevention and Control of Cancer in the Americas.Three case studies are presented to illustrate the impact of specific environmental and occupational agents and the challenge of control.There are still fully avoidable exposures to carcinogens, as well documented in the case of asbestos in Brazil. Thus, there are abundant targets for intervention to reduce cancer in the Americas.Los agentes ambientales y ocupacionales son causas de cáncer y enfermedades en todo el mundo, mientras que su control y reducción de la carga de enfermedad asociada siguen siendo puntos complejos.Este documento resume el estado actual de la carga de las causas ambientales y ocupacionales de las enfermedades en las Américas a partir de las presentaciones de un panel sobre medio ambiente, ocupación y otros factores de riesgo ambientales para el cáncer en las Américas, realizado en Panamá, en la conferencia internacional Promoviendo la Equidad en Salud y las Colaboraciones Transnacionales para la Prevención y el Control del Cáncer en las Américas.Se presentan tres estudios de caso para ilustrar el impacto de agentes ambientales y ocupacionales específicos y el desafío del control.Todavía hay exposiciones totalmente evitables a los carcinógenos, como está bien documentado en el caso del asbesto en Brasil. Hay abundantes puntos estratégicos de intervención para reducir el cáncer en las Américas.

Background We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ. Materials and methods Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC. Results CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings. Conclusion We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.

In the version of this article originally published, the names of the equally contributing authors and jointly supervising authors were switched. The correct affiliations are: “These authors contributed equally: David V. Conti, Burcu F. Darst. These authors jointly supervised this work: David V. Conti, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman.” The error has been corrected in the HTML and PDF versions of the article.

International audience; Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Background: Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. Patients and methods: We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Results: Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 mg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. Conclusions: This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer. © The Author 2016.

Low unit response rates can increase bias and compromise study validity. Response rates have continued to fall over the past decade despite all efforts to increase participation. Many factors have been linked to reduced response, yet relatively few studies have employed multivariate approaches to identify characteristics that differentiate respondents from nonrespondents since it is hard to collect information on the latter. We aimed to assess factors contributing to enrollment of prostate cancer (PCa) patients. We combined data from the North Carolina-Louisiana (LA) PCa Project's LA cohort, with additional sources such as US census tract and LA tumor registry data. We included specific analyses focusing on blacks, a group often identified as hard to enroll in health-related research. The ability to study the effect of Hurricane Katrina, which occurred amidst enrollment, as a potential determinant of nonresponse makes our study unique. Older age (≥ 70) for blacks (OR 0.65) and study phase with respect to Hurricane Katrina for both races (OR 0.59 for blacks, OR 0.48 for whites) were significant predictors of participation with lower odds. Neighborhood poverty for whites (OR 1.53) also was a significant predictor of participation, but with higher odds. Among blacks, residence in Orleans parish was associated with lower odds of participation (OR 0.33) before Katrina. The opposite occurred in whites, with lower odds (OR 0.43) after Katrina. Our results overall underscore the importance of tailoring enrollment approaches to specific target population characteristics to confront the challenges posed by nonresponse. Our results also show that recruitment-related factors may change when outside forces bring major alterations to a population's environment and demographics.

Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for =15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for

To examine the association between socio-cultural factors and patient-provider communication and related racial differences.Data analysis included 1854 men with prostate cancer from a population-based study. Participants completed an assessment of communication variables, physician trust, perceived racism, religious beliefs, traditional health beliefs, and health literacy. A multi-group structural equation modeling approach was used to address the research aims.Compared with African Americans, Caucasian Americans had significantly greater mean scores of interpersonal treatment (p0.01), prostate cancer communication (p0.001), and physician trust (p0.001), but lower mean scores of religious beliefs, traditional health beliefs, and perceived racism (all p values0.001). For both African and Caucasian Americans, better patient-provider communication was associated with more physician trust, less perceived racism, greater religious beliefs (all p-values0.01), and at least high school education (p0.05).Socio-cultural factors are associated with patient-provider communication among men with cancer. No evidence supported associations differed by race.To facilitate patient-provider communication during prostate cancer care, providers need to be aware of patient education levels, engage in behaviors that enhance trust, treat patients equally, respect religious beliefs, and reduce the difficulty level of the information.

To examine the multidimensional concept of patient-health care provider (HCP) communication, its effects on patient satisfaction with oncology care services, and related racial differences.The current analysis draws from a population-based survey sample of 1011 African American and 1034 Caucasian American men with newly diagnosed prostate cancer. The variables of satisfaction with health care services, interpersonal treatment, contextual knowledge of the patient, and prostate cancer communication were analyzed using multiple-group structural equation modeling.Regardless of race, patient-HCP communication was related positively to interpersonal treatment by the HCP, HCP's contextual knowledge of the patient, and prostate cancer communication. More positive patient-HCP communication was related to more satisfaction with health care services. Racial differences were significant in the relationships between patient-HCP communication and prostate cancer communication.Content and interpersonal relationships are important aspects of patient-HCP communication and affect patient satisfaction with oncologic care for prostate cancer.HCPs need to integrate the transfer of information with emotional support and interpersonal connection when they communicate with men with newly diagnosed prostate cancer.

Bosetti, C Lucenteforte, E Bracci, P M Negri, E Neale, R E Risch, H A Olson, S H Gallinger, S Miller, A B Bueno-de-Mesquita, H B Talamini, R Polesel, J Ghadirian, P Baghurst, P A Zatonski, W Fontham, E Holly, E A Gao, Y T Yu, H Kurtz, R C Cotterchio, M Maisonneuve, P Zeegers, M P Duell, E J Boffetta, P La Vecchia, C eng 5R01-CA098870/CA/NCI NIH HHS/ CA098889/CA/NCI NIH HHS/ CA108370/CA/NCI NIH HHS/ CA109767/CA/NCI NIH HHS/ CA59706/CA/NCI NIH HHS/ CA89726/CA/NCI NIH HHS/ N01-PC-35136/PC/NCI NIH HHS/ R01 CA97075/CA/NCI NIH HHS/ U01 CA074783/CA/NCI NIH HHS/ U01-CA74783/CA/NCI NIH HHS/ U24 CA074783/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2013/08/24 06:00 Ann Oncol. 2013 Nov;24(11):2903-10. doi: 10.1093/annonc/mdt336. Epub 2013 Aug 22.; International audience; BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

Background: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. Materials and methods: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11 338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. Results: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipeonly smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for = 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). Conclusion: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Disasters and their environmental and health consequences know no bounds. Although no geographic area or population is exempt from natural or manmade disasters, Louisiana and its neighboring coastal states on the Gulf of Mexico have had more than their fair share over the past 5 years. The latest environmental disaster is the BP Deepwater Horizon oil spill, which began on 20 April 2010, < 5 years after Hurricanes Katrina and Rita wreaked havoc in the same area. The effects of hurricanes, which are annual events, are relatively well understood, but the environmental and human health effects of oil spills are much less so. The amount of oil released from the spill site peaked at about 62,000 barrels/day (Robertson and Krauss 2010) until the well was permanently capped on 15 July 2010. The U.S. Geological Survey (USGS 2010) estimated that as of 1 August 2010, 4.4–5.4 million barrels of oil were released. In addition, approximately 1 billion ft3 of natural gas has been flared, well over 265,000 barrels of oil have been burned, and > 1.8 million gallons of dispersant (primarily Corexit 9500 but also Corexit 9527) have been applied. More than 52,000 workers have been involved with spill training and cleanup efforts [National Institute for Occupational Safety and Health (NIOSH) 2010a], and BP estimates that the cleanup is about 90% complete (Heron R, personal communication). However, others question this estimate [Georgia Sea Grant 2010; National Oceanic and Atmospheric Administration (NOAA) 2010]. In addition, there are concerns about effects of oil on oxygen levels in the water and the ability of bacteria and other organisms to break down oil and dispersants at all water depths. Data are available on acute health effects in humans exposed to 7 of 39 large oil spills documented throughout the world (reviewed by Aguilera et al. 2010). These relatively short-term cross-sectional studies have documented acute disorders, including low back pain, headache, inflammation of the eyes and throat, nausea, injuries, lower respiratory tract effects, and psychological effects including depression. To date, workers involved in fishing and clean-up in Louisiana—the most heavily impacted state—have reported headaches, nausea, breathing difficulties, cough, throat irritation, eye irritation, and injuries (Lousiana Department of Health and Hospitals 2010) consistent with acute effects documented in past spills (Aguilera et al. 2010). As of 8–14 August 2010, 376 persons in Louisiana had reported health complaints. Nationally, there have been 2,130 acute health complaints related to this spill (NIOSH 2010b), and as of 7 September 2010, U.S. poison centers had taken 1,155 calls concerning exposure to an oil spill–related toxicant, such as oil, dispersant, contaminated food, or associated toxicants (American Association of Poison Control Centers 2010). In addition, two studies have reported that mental stress and physical symptoms have been experienced by 35–45% of Gulf Coast respondents (Abramson et al. 2010; Lee et al. 2010). Heavy fuel oils are classified as possible human carcinogens [International Agency for Research on Cancer (IARC) 1989], and there is ample evidence in laboratory animal studies that heavy oil is carcinogenic (Marathon Petroleum Company 2005). Further, many individual substances found in crude oil, including benzene, benzo[a]pyrene, and arsenic are class 1 human carcinogens (IARC, in press), and other chemicals in the oil and dispersants may also be carcinogenic. In addition, exposure to heavy oil and related contaminants may be able to increase cancer risk indirectly through, for example, mechanisms related to stress (Reiche et al. 2004), immunosuppression (Grulich et al. 2007), or endocrine disruption (Soto and Sonnenschein 2010). Although long-term follow-up is essential to assess potential impacts of oil spill exposures on cancer and other chronic diseases, essentially no long-term epidemiologic studies have been reported in the literature, nor has population research been conducted on the health effects of exposure to oil, its breakdown products, and dispersants via the food chain. Long-term study is also needed to examine effects of these exposures on pregnant women and their infants. Bis(2-ethylhexyl) phthalate, which is present in both Corexit 9500 and Corexit 9527, has been associated with testicular effects, fertility, toxicity to kidneys, and cancer (Agency for Toxic Substances and Disease Registry 2002; Tickner et al. 2001). Benzene exposure during pregnancy has been associated with low birth weight and childhood leukemia, and exposures to polyaromatic hydrocarbon have been associated with low birth weight and small head circumference (Slama et al. 2009; U.S. Environmental Protection Agency 2009); other outcomes of potential concern include spontaneous abortion, birth defects, and aneuploidy (Eskenazi B, personal communication). There are many challenges to designing and performing optimal epidemiologic studies in this environment: Meaningful community involvement is essential so concerns can be addressed, and accurate documentation is needed for individuals involved in spill cleanup or who live in the impacted areas (e.g., a register). This cohort should include oil rig and response workers (both exposed and presumably unexposed workers); cleanup workers on ships and on the shore; first responders, including health care workers; and representative individuals and families from the general population, with special attention to those involved in maritime/marine activities. A cohort study requires a long-term commitment from both study participants and researchers, and it must represent rigorous science and be conducted in a manner that protects the rights of individual participants. A study of this cohort should include quantitative exposure estimation through biomonitoring, genotoxicity studies, risk assessments, and other techniques, and determination of intermediate and long-term effects; it should also assess the potential for ongoing exposures via contamination of the food chain and the disposal of oil/dispersant–soaked material in landfills or through burning. Exposure is time dependent; thus, identification and enrollment of the workers, their families, and the communities need to begin now with the collection of basic epidemiologic, occupational, and baseline health data, as well as collection and banking of biological samples from participants. A multidisciplinary team of scientists, including epidemiologists, biostatisticians, biochemists, and other environmental scientists, is needed to contribute to the design, conduct, and interpretation of these human health studies. It is both reasonable and responsible to be concerned about cancer and other diseases of long latency arising from this unfortunate incident, and we have the tools and expertise to evaluate these health concerns throughout the impacted states. All parties must act with expedience, professionalism, and commitment to the populations of the Gulf South.