Opportunities for Cancer Prevention During Midlife Highlights from a Meeting of Experts

AbstractThis paper provides highlights from a CDC-hosted meeting on opportunities for cancer prevention during midlife (roughly ages 45–64 years). Positive changes during this phase of life have the potential to prevent cancer incidence later in life, making this phase an opportune time for targeted prevention efforts to facilitate healthy aging and increased longevity. Risk and protective factors discussed during the meeting included exposure to radiation from medical imaging procedures, circadian disruption, chemical exposures, dietary factors, alcohol consumption, obesity, physical activity, diabetes, and the human microbiome. Although many of these factors are well recognized as being related to cancer incidence, others are not as widely recognized or have emerged as growing areas of research.Meeting participants discussed promising strategies for cancer prevention targeting this age group. Just as there are multiple determinants of cancer risk, there are likely multiple solutions. Changes to social and physical environments may facilitate healthy behaviors and minimize harmful exposures. Information shared during the meeting about health disparities in the U.S. highlighted the need to go beyond traditional approaches to cancer prevention to truly reach vulnerable populations. Partnerships are also a key component to prevention efforts; community-based and nonprofit organizations, the healthcare system, research institutions, state health departments, and federal agencies were all noted as important partners in prevention efforts. Coordinated, multi-disciplinary efforts across multiple chronic diseases may provide opportunities for synergistic effects. Further, leveraging key partnerships and existing communication channels can maximize success and facilitate timely translation of research findings into public health practice

Lung cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study.

BACKGROUND: Results from the second CONCORD study (CONCORD-2) indicated that 5-year net survival for lung cancer was low (range, 10%-20%) between 1995 and 2009 in most countries, including the United States, which was at the higher end of this range. METHODS: Data from CONCORD-2 were used to analyze net survival among patients with lung cancer (aged 15-99 years) who were diagnosed in 37 states covering 80% of the US population. Survival was corrected for background mortality using state-specific and race-specific life tables and age-standardized using International Cancer Survival Standard weights. Net survival was estimated for patients diagnosed between 2001 and 2003 and between 2004 and 2009 at 1, 3, and 5 years after diagnosis by race (all races, black, and white); Surveillance, Epidemiology, and End Results Summary Stage 2000; and US state. RESULTS: Five-year net survival increased from 16.4% (95% confidence interval, 16.3%-16.5%) for patients diagnosed 2001-2003 to 19.0% (18.8%-19.1%) for those diagnosed 2004-2009, with increases in most states and among both blacks and whites. Between 2004 and 2009, 5-year survival was lower among blacks (14.9%) than among whites (19.4%) and ranged by state from 14.5% to 25.2%. CONCLUSIONS: Lung cancer survival improved slightly between the periods 2001-2003 and 2004-2009 but was still low, with variation between states, and persistently lower survival among blacks than whites. Efforts to control well established risk factors would be expected to have the greatest impact on reducing the burden of lung cancer, and efforts to ensure that all patients receive timely and appropriate treatment should reduce the differences in survival by race and state. Cancer 2017;123:5079-99. Published 2017. This article is a U.S. Government work and is in the public domain in the USA

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Role of smoking in global and regional cancer epidemiology: current patterns and data needs

Although smoking is widely recognized as a major cause of cancer, there is little information on how it contributes to the global and regional burden of cancers in combination with other risk factors that affect background cancer mortality patterns. We used data from the American Cancer Society's Cancer Prevention Study II (CPS-II) and the WHO and IARC cancer mortality databases to estimate deaths from 8 clusters of site-specific cancers caused by smoking, for 14 epidemiologic subregions of the world, by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS-II hazards were adjusted for important covariates. In the year 2000, an estimated 1.42 (95% CI 1.27-1.57) million cancer deaths in the world, 21% of total global cancer deaths, were caused by smoking. Of these, 1.18 million deaths were among men and 0.24 million among women; 625,000 (95% CI 485,000-749,000) smoking-caused cancer deaths occurred in the developing world and 794,000 (95% CI 749,000-840,000) in industrialized regions. Lung cancer accounted for 60% of smoking-attributable cancer mortality, followed by cancers of the upper aerodigestive tract (20%). Based on available data, more than one in every 5 cancer deaths in the world in the year 2000 were caused by smoking, making it possibly the single largest preventable cause of cancer mortality. There was significant variability across regions in the role of smoking as a cause of the different site-specific cancers. This variability illustrates the importance of coupling research and surveillance of smoking with that for other risk factors for more effective cancer prevention. (C) 2005 Wiley-Liss, Inc

How many deaths are attributable to smoking in the United States? Comparison of methods for estimating smoking-attributable mortality when smoking prevalence changes

Background: The number of smoking-attributable deaths is commonly estimated using current and former smoking prevalences or lung cancer mortality as an indirect metric of cumulative population smoking. Neither method accounts for differences in the timing with which relative risks (RRs) for different diseases change following smoking initiation and cessation. We aimed to develop a method to account for time-dependent RRs. Methods: We used birth cohort lung cancer mortality and its change over time to characterize time-varying cumulative smoking exposure. We analyzed data from the American Cancer Society Cancer Prevention Study II to estimate RRs for disease-specific mortality associated with current and former smoking, and change in RRs over time after cessation. Results: When lung cancer was used to measure cumulative smoking exposure, 254,700 male and 227,000 female deaths were attributed to smoking in the US in 2005. A modified method in which RRs for different diseases decreased at different rates after cessation yielded similar but slightly lower estimates [251,900 (male) and 221,100 (female)]. The lowest estimates resulted from the method based on smoking prevalence [225,800 (male) and 163,700 (female)]. Conclusions: Although all methods estimated a large number of smoking attributable deaths, future efforts should account for temporal changes in smoking prevalence and in accumulation/reversibility of disease-specific risks