Purpose: Dietary intake of long-chain Ï-3 (LC n-3) polyunsaturated fatty acids may reduce inflammation and in turn decrease risk of
prostate cancer development and progression. This potential effect ...may be modified by genetic variation in cyclooxygenase-2 ( COX-2 ), a key enzyme in fatty acid metabolism and inflammation.
Experimental Design: We used a case-control study of 466 men diagnosed with aggressive prostate cancer and 478 age- and ethnicity-matched controls.
Diet was assessed with a semiquantitative food frequency questionnaire, and nine COX-2 tag single nucleotide polymorphisms (SNP) were genotyped. We used logistic regression models to estimate odds ratios (OR)
for association and interaction.
Results: Increasing intake of LC n-3 was strongly associated with a decreased risk of aggressive prostate cancer ( P trend ⤠0.0001). The OR (95% confidence interval) for prostate cancer comparing the highest with the lowest quartile of n-3 intake
was of 0.37 (0.25-0.54). The LC n-3 association was modified by SNP rs4648310 (+8897 A/G), flanking the 3â² region of COX-2 ( P interaction = 0.02). In particular, the inverse association was even stronger among men with this variant SNP. This reflected the observation
that men with low LC n-3 intake and the variant rs4648310 SNP had an increased risk of disease (OR, 5.49; 95% confidence interval,
1.80-16.7), which was reversed by increasing intake of LC n-3.
Conclusions: Dietary LC n-3 polyunsaturated fatty acids appear protective for aggressive prostate cancer, and this effect is modified
by the COX-2 SNP rs4648310. Our findings support the hypothesis that LC n-3 may impact prostate inflammation and carcinogenesis through
the COX-2 enzymatic pathway.
Colorectal cancer (CRC) incidence and mortality rates vary across race/ethnicity. Socioeconomic status (SES) also influences CRC rates; however, these associations might be inconsistent across ...racial/ethnic groups and tumor subsite. We examined associations between area-level SES and CRC incidence and mortality in a population-based registry study of non-Hispanic Whites, African Americans, Hispanics, and Asians/Pacific Islanders from California.
Data on 52,608 incident CRC cases (1998-2002) and 14,515 CRC deaths (1999-2001) aged ≥50 years were obtained from the California Cancer Registry. Based on 2000 U.S. Census data, each cancer case and death was assigned a multidimensional census tract-level SES index. SES-specific quintiles of CRC incidence and mortality rates, incidence rate ratios (IRR) and mortality rate ratios, and 95% confidence intervals (CI) were estimated. Analyses were stratified by anatomical site, including left- versus right-sided tumors, race/ethnicity, and stage of disease.
Overall CRC incidence and SES did not show a clear association, yet patterns of associations varied across tumor subsite and race/ethnicity. Positive associations between SES and CRC incidence were found in Hispanics SES Q5 v. Q1: IRR = 1.54, CI = 1.39-1.69, irrespective of the subsite. For Whites SES Q5 v. Q1: IRR = 0.80, CI = 0.77-0.83, and African Americans SES Q5 v. Q1: IRR = 0.83, CI = 0.70-0.97 inverse associations were observed, predominantly for left-sided tumors. Mortality rates declined with increasing SES in Whites, whereas in Hispanics mortality rates significantly increased with SES.
Our findings show that SES differences in CRC incidence and mortality vary considerably across anatomical subsite and race/ethnicity.
Studies combining area- and individual-level SES information are warranted.
Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans.
We further evaluated this G84E missense mutation (rs138213197) in two ...genetic association studies of prostate cancer: a family-based study of brothers and a case-control study of more aggressive disease (N = 2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans.
In our studies, the mutation was found exclusively among men with prostate cancer (carrier frequency = 1.48%) or unaffected brothers of cases carrying the mutation (frequency = 0.34%), and carrying the mutation gave an OR for disease = 4.79 (P = 0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P = 3.5 × 10(-17)), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P < 1 × 10(-5).
The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men.
Testing for the G84E mutation in men with a positive family history may help distinguish those who merit more regular screening for prostate cancer.
Increased exposure of colonic and rectal epithelial cells to the promitotic and antiapoptotic effects of insulin and insulin-like growth factors (IGF) is hypothesized to increase colorectal cancer ...risk.
In a case-control study nested within the Multiethnic Cohort, we attempted to replicate associations for five genetic variants associated with IGF system biomarkers, insulin, or glucose and to examine their association with the risk of colorectal cancer. In a subset of participants, the association between circulating biomarkers and colorectal cancer risk was examined. Unconditional logistic regression was used to calculate ORs and 95% confidence intervals (CI) for genetic variants (1,954 cases/2,587 controls) and serum biomarkers (258 cases/1,701 controls).
Associations with circulating biomarkers were replicated in the Multiethnic Cohort for IGF1 rs35767 and for IGFBP3 rs2854744, rs2854746, and rs3110697 (P < 0.05). Homozygous carriers of the glucokinase regulator (GCKR) rs780094 variant T-allele were at a decreased risk of colorectal cancer (OR, 0.77; 95% CI, 0.64-0.92). In risk factor-adjusted models, participants with the highest prediagnostic IGF-II levels were at an increased risk OR (T1 vs. T3), 1.58; 95% CI, 1.09-2.28; P(trend) = 0.011 and participants with the highest prediagnostic IGF-binding protein (IGFBP)-3 levels were at a decreased risk of colorectal cancer (OR, 0.53; 95% CI, 0.34-0.83; P(trend) = 0.003).
These data provide further support for a role of prediagnostic IGF and insulin levels in the etiology of colorectal cancer.
Future studies attempting to replicate the association between the GCKR rs780094 variant and the risk of colorectal cancer are warranted.
Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNP) associated with the risk of prostate cancer. Our objective was to determine whether these SNPs affect ...the progression of prostate cancer.
We genotyped 26 SNPs previously associated with prostate cancer risk among 788 aggressive prostate cancer patients who were treated by radical prostatectomy or radiation therapy. Prostate cancer progression was defined as biochemical recurrence based on posttreatment prostate-specific antigen levels of >0.3 ng/mL for radical prostatectomy patients or a 2-ng/mL increase above the nadir for radiation therapy patients, initiation of hormone treatment, or metastases. We assessed the association between independent and combined SNPs and disease progression by Cox proportional hazards regression.
Five SNPs showed independent associations with prostate cancer progression (rs12621278, rs629242, rs9364554, rs4430796, and rs5945572) based on stepwise regression analysis. The strongest SNP was rs12621278 in the ITGA6 locus, which was associated with a 2.4-fold increased risk of progression (P = 0.0003). When considering the sum of risk alleles across these five SNPs, each additional allele was associated with a 29% increase in risk of progression (95% confidence interval, 1.12-1-47).
We found that five of the recently highlighted prostate cancer susceptibility loci also influence prostate cancer progression beyond the known clinicopathologic predictors. If confirmed, these genetic variants might help clarify which tumors are likely to progress and require more aggressive treatment in contrast to those that might not have substantial effects on morbidity or mortality.
Genetic susceptibility variants for prostate cancer development may also inform disease progression.
Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the ...associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (βmeta = 0.2244 (standard error, 0.0548); P = 4 × 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (βmeta = -0.2796 (standard error, 0.0709); P = 8 × 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.
Purpose We analyzed the risk of dying of a second cancer after radical prostatectomy for clinically localized prostate cancer. Materials and Methods We studied 1,910 patients who consecutively ...underwent radical prostatectomy between 1992 and 2004. These patients had a median age of 65 years, a median prostate specific antigen of 7.6 ng/ml and a median followup of 5.9 years. Overall disease specific, comorbid, second cancer specific and other mortality data were used as study end points in competing risk analyses. Fatal second cancers were subdivided into 10 categories. The numbers of observed deaths from second cancers were compared with expected rates using cancer registry data. Results The risk of dying of a second cancer within 10 years after radical prostatectomy was 4.1%. This death rate was lower than that of comorbidity (5.8%) and prostate cancer (5.4%). Among second cancers colorectal cancer (0.74%), lung cancer (0.69%) and lymphoma, myeloma or leukemia (0.66%) were the most common causes of death after 10 years. Whereas the mortality rates from the other second cancers were within the expected range, fatal lung cancer occurred significantly less frequently than expected. Conclusions The low probability of dying of a second malignancy within 10 years after surgery (about 4%) and the nevertheless relatively large contribution of second cancers to competing mortality (about 40%) reflect the good general health status of men selected for radical prostatectomy.
To understand hospital policies and practices as the COVID-19 pandemic accelerated, the Society for Healthcare Epidemiology of America (SHEA) conducted a survey through the SHEA Research Network ...(SRN). The survey assessed policies and practices around the optimization of personal protection equipment (PPE), testing, healthcare personnel policies, visitors of COVID-19 patients in relation to procedures, and types of patients. Overall, 69 individual healthcare facilities responded in the United States and internationally, for a 73% response rate.
OBJECTIVEMultidrug-resistant organisms (MDROs) are increasingly reported in residential care homes for the elderly (RCHEs). We assessed whether implementation of directly observed hand hygiene (DOHH) ...by hand hygiene ambassadors can reduce environmental contamination with MDROs.METHODSFrom July to August 2017, a cluster-randomized controlled study was conducted at 10 RCHEs (5 intervention versus 5 nonintervention controls), where DOHH was performed at two-hourly intervals during daytime, before meals and medication rounds by a one trained nurse in each intervention RCHE. Environmental contamination by MRDOs, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum β-lactamse (ESBL)-producing Enterobacteriaceae, was evaluated using specimens collected from communal areas at baseline, then twice weekly. The volume of alcohol-based hand rub (ABHR) consumed per resident per week was measured.RESULTSThe overall environmental contamination of communal areas was culture-positive for MRSA in 33 of 100 specimens (33%), CRA in 26 of 100 specimens (26%), and ESBL-producing Enterobacteriaceae in 3 of 100 specimens (3%) in intervention and nonintervention RCHEs at baseline. Serial monitoring of environmental specimens revealed a significant reduction in MRSA (79 of 600 13.2% vs 197 of 600 32.8%; P<.001) and CRA (56 of 600 9.3% vs 94 of 600 15.7%; P=.001) contamination in the intervention arm compared with the nonintervention arm during the study period. The volume of ABHR consumed per resident per week was 3 times higher in the intervention arm compared with the baseline (59.3±12.9 mL vs 19.7±12.6 mL; P<.001) and was significantly higher than the nonintervention arm (59.3±12.9 mL vs 23.3±17.2 mL; P=.006).CONCLUSIONSThe direct observation of hand hygiene of residents could reduce environmental contamination by MDROs in RCHEs.Infect Control Hosp Epidemiol 2018;39:571-577.
Abstract
Background
Most nursing facilities (NFs) lack methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) surveillance programs due to limited resources ...and high costs. We investigated the utility of environmental screening of high-touch surfaces in patient rooms as a way to circumvent these challenges.
Methods
We compared MRSA and VRE culture data from high-touch surfaces in patients' rooms (14450 samples from 6 NFs) and ranked each site's performance in predicting patient colonization (7413 samples). The best-performing sites were included in a MRSA- and a VRE-specific panel that functioned as a proxy for patient colonization. Molecular typing was performed to confirm available concordant patient-environment pairs.
Results
We identified and validated a MRSA panel that consisted of the bed controls, nurse call button, bed rail, and TV remote control. The VRE panel included the toilet seat, bed controls, bed rail, TV remote control, and top of the side table. Panel colonization data tracked patient colonization. Negative predictive values were 89%-92% for MRSA and 82%-84% for VRE. Molecular typing confirmed a strong clonal type relationship in available concordant patient-environment pairs (98% for MRSA, 91% for VRE), pointing to common epidemiological patterns for environmental and patient isolates.
Conclusions
Environmental panels used as a proxy for patient colonization and incorporated into facility surveillance protocols can guide decolonization strategies, improve awareness of MRSA and VRE burden, and inform efforts to reduce transmission. Targeted environmental screening may be a viable surveillance strategy for MRSA and VRE detection in NFs.
Surveillance for antimicrobial-resistant organisms in nursing facilities is critically important but challenging. We developed simple panels of environmental sites that can be used as a proxy for determining nursing facility patient methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus colonization.