Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30. © 2017 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21387

Cancer statistics, 2017

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

/pdf/meta-analysis-of-74-046-individuals-identifies-11-new-406eax0kye.pdf

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

The Rotterdam study

Background: Sequence variants, including the e4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease. Few rare variants affecting the risk of late-onset Alzheimer's disease have been found. Methods: We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer's disease and control participants and then tested for an association with Alzheimer's disease. We performed replication tests using case-control series from the United States, Norway, the Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. Results: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P = 3.42×10-10). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P = 2.1×10-12 in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P = 0.003). Conclusions: Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.) Copyright

/pdf/variant-of-trem2-associated-with-the-risk-of-alzheimer-s-2dn9pht6fo.pdf

Variant of TREM2 associated with the risk of Alzheimer's disease

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.

/pdf/the-rotterdam-study-objectives-and-design-update-2n3pqovgsq.pdf

The Rotterdam Study: Objectives and design update

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)-1β, IL-6, IL-10, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, E-selectin and tumour necrosis factor (TNF)-α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random-effects model. Seventy-eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL-6 [d = 1·32, 95% confidence interval (CI) 0·83-1·81], CRP (d = 1·83, 95% CI 0·76-2·90), TNF-α (d = 1·32, 95% CI 0·86-1·79), E-selectin (d = 1·78, 95% CI 1·32-2·25) and ICAM-1 (d = 1·77, 95% CI 1·15-2·39). The SMD between cases and controls for IL-1β and IL-10 was not significant. Age had a significant effect on the SMD for IL-6 and TNF-α. For IL-6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy. What's already known about this topic? Psoriasis is an inflammatory disease affecting the skin. Many studies have investigated whether it can also be considered a systemic disease, by analysing serum levels of inflammatory cytokines in patients with psoriasis. What does this study add? This study systematically synthesizes the evidence on selected serum inflammatory markers to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjd.12355

Markers of systemic inflammation in psoriasis: A systematic review and meta-analysis

Prevalence of actinic keratosis and its risk factors in the general population: The rotterdam study

Basal cell carcinoma (BCC) is the most common cancer in white-skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation (UVR) related skin cancers (i.e. field cancerization). As a result, the disability-adjusted life years and healthcare costs have risen significantly in recent decades. BCC is a complex disease, in which the interplay between UVR, phenotype (UVR-sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis. Prevention programmes with continual refinements and improvements could be of major importance in tackling the growing skin cancer problem. To provide the most appropriate BCC care, physicians should engage in shared decision-making and choose their treatments wisely.

Epidemiology of basal cell carcinoma: scholarly review.

https://www.jidonline.org/article/S0022-202X(15)34794-1/pdf

Tamar Nijsten

Papers

The Rotterdam Study: Objectives and design update

Markers of systemic inflammation in psoriasis: A systematic review and meta-analysis

Prevalence of actinic keratosis and its risk factors in the general population: The rotterdam study

Epidemiology of basal cell carcinoma: scholarly review.

Psoriasis May Not be an Independent Risk Factor for Acute Ischemic Heart Disease Hospitalizations: Results of a Large Population-Based Dutch Cohort