A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

IMPORTANCE Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer.OBJECTIVE To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene × environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTSCase-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent.EXPOSURES Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. MAIN OUTCOMES AND MEASURES Colorectal cancer.RESULTS Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P = 6.2 × 10 −28 ) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 × 10 −9 for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P = 7.7 × 10 −33 ) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 × 10 −9 for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 × 10 −30 ) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P = .76). CONCLUSIONS AND RELEVANCEIn this genome-wide investigation of gene × environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.

Purpose Earlier Women's Health Initiative Dietary Modification trial findings suggested that a low-fat eating pattern may reduce breast cancers with greater mortality. Therefore, as a primary outcome-related analysis from a randomized prevention trial, we examined the long-term influence of this intervention on deaths as a result of and after breast cancer during 8.5 years (median) of dietary intervention and cumulatively for all breast cancers diagnosed during 16.1 years (median) of follow-up. Patients and MethodsThe trial randomly assigned 48,835 postmenopausal women with normal mammograms and without prior breast cancer from 1993 to 1998 at 40 US clinical centers to a dietary intervention with goals of a reduction of fat intake to 20% of energy and an increased intake of fruits, vegetables, and grains (40%; n = 19,541) or to a usual diet comparison (60%; n = 29,294). ResultsIn the dietary group, fat intake and body weight decreased (all P , .001). During the 8. ConclusionCompared with a usual diet comparison group, a low-fat dietary pattern led to a lower incidence of deaths after breast cancer.

In healthy adults from the general population, we found a significant and robust association between depression and anemia. Further studies are needed to assess the longitudinal relationship between both conditions and determine the mechanisms underlying this association.

We assessed the role of four candidate genes encoding proteins involved in dopaminergic transmission, the dopamine transporter (DAT), the dopamine receptor D2 (DRD2), and the main catabolic enzymes of dopamine, monoamine oxidase A (MAOA) and B (MAOB), through allelic association studies in a population of familial and sporadic Parkinson's disease (PD). Using intronic polymorphisms of the four candidate genes, we studied the allelic distributions of the polymorphic markers in 18 affected members, one patient was chosen randomly from each PD family; 60 sporadic PD and 60 healthy unrelated control subjects were matched for sex and for country of origin. All subjects were white. To complete the study of the DRD2, we subsequently tested 40 additional sporadic PD and 40 control patients, who were recruited using a similar procedure. For DAT, MAOA, MAOB polymorphisms, similar allelic frequencies were present in familial, sporadic PD and control patients. In contrast, at the DRD2 locus, the overall allelic distribution was significantly different in the sporadic PD (p < 0.01) and in the familial PD groups (p < 0.05), each was compared with the controls. The odd ratios were significant (p < 0.01) in sporadic PD and in familial PD for allele 3 with respective values of 1.84 (95% CI, 1.23-2.74) and 2.83 (95% CI, 1.32-6.08). Individuals who were homozygous for allele 3 were 2.3 times more frequent in the sporadic PD than in controls. Results suggest that DRD2, but not DAT, MAOA and MAOB, might be a genetic determinant of PD in the population tested.

BackgroundThe aim of this study was to investigate the association of gene expression profiles in subcutaneous adipose tissue with weight change in kidney transplant recipients and to gain insights into the underlying mechanisms of weight gain.Methodology/Principal FindingsA secondary data analysis was done on a subgroup (n = 26) of existing clinical and gene expression data from a larger prospective longitudinal study examining factors contributing to weight gain in transplant recipients. Measurements taken included adipose tissue gene expression profiles at time of transplant, baseline and six-month weight, and demographic data. Using multivariate linear regression analysis controlled for race and gender, expression levels of 1553 genes were significantly (p<0.05) associated with weight change. Functional analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes classifications identified metabolic pathways that were enriched in this dataset. Furthermore, GeneIndexer literature mining analysis identified a subset of genes that are highly associated with obesity in the literature and Ingenuity pathway analysis revealed several significant gene networks associated with metabolism and endocrine function. Polymorphisms in several of these genes have previously been linked to obesity.Conclusions/SignificanceWe have successfully identified a set of molecular pathways that taken together may provide insights into the mechanisms of weight gain in kidney transplant recipients. Future work will be done to determine how these pathways may contribute to weight gain.

Background Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer. What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for colorectal cancer modify this association. Methods We performed a pooled analysis of 8 studies, including 6,796 colorectal cancer cases and 7,770 controls to evaluate the association between cigarette smoking history and colorectal cancer risk, and to investigate potential effect modification by other risk factors. Results Current smokers (OR=1.26, 95% CI=1.11–1.43) and former smokers (OR=1.18, 95% CI=1.09–1.27), relative to never smokers, showed higher risks of colorectal cancer. Former smokers remained at higher colorectal cancer risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: the excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer, but not until about 20 years post-quitting for distal colon cancer. Further, we observed borderline statistically significant additive interactions between smoking status and BMI (relative excess risk due to interaction [RERI]=0.15, 95% CI:−0.01–0.31, P=0.06) and significant additive interaction between smoking status and fruit consumption (RERI=0.16, 95% CI: 0.01–0.30, P=0.04). Conclusion Colorectal cancer risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking. Impact These results contribute to a better understanding of the mechanisms through which smoking impacts colorectal cancer etiology.

Since its global emergence in 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused multiple epidemics in the United States. Because medical treatments for the virus are still emerging and a vaccine is not yet available, state and local governments have sought to limit its spread by enacting various social distancing interventions such as school closures and lockdown, but the effectiveness of these interventions is unknown. We applied an established, semi-mechanistic Bayesian hierarchical model of these interventions on SARS-CoV-2 spread in Europe to the United States, using case fatalities from February 29, 2020 up to April 25, 2020, when some states began reversing their interventions. We estimated the effect of interventions across all states, contrasted the estimated reproduction number, Rt, for each state before and after lockdown, and contrasted predicted future fatalities with actual fatalities as a check on the model’s validity. Overall, school closures and lockdown are the only interventions modeled that have a reliable impact on Rt, and lockdown appears to have played a key role in reducing Rt below 1.0. We conclude that reversal of lockdown, without implementation of additional, equally effective interventions, will enable continued, sustained transmission of SARS-CoV-2 in the United States.