David P. Check

Importance: Thyroid cancer incidence has increased substantially in the United States over the last 4 decades, driven largely by increases in papillary thyroid cancer. It is unclear whether the increasing incidence of papillary thyroid cancer has been related to thyroid cancer mortality trends. Objective: To compare trends in thyroid cancer incidence and mortality by tumor characteristics at diagnosis. Design, Setting, and Participants: Trends in thyroid cancer incidence and incidence-based mortality rates were evaluated using data from the Surveillance, Epidemiology, and End Results-9 (SEER-9) cancer registry program, and annual percent change in rates was calculated using log-linear regression. Exposure: Tumor characteristics. Main Outcomes and Measures: Annual percent changes in age-adjusted thyroid cancer incidence and incidence-based mortality rates by histologic type and SEER stage for cases diagnosed during 1974-2013. Results: Among 77 276 patients (mean [SD] age at diagnosis, 48 [16] years; 58 213 [75%] women) diagnosed with thyroid cancer from 1974-2013, papillary thyroid cancer was the most common histologic type (64 625 cases), and 2371 deaths from thyroid cancer occurred during 1994-2013. Thyroid cancer incidence increased, on average, 3.6% per year (95% CI, 3.2%-3.9%) during 1974-2013 (from 4.56 per 100 000 person-years in 1974-1977 to 14.42 per 100 000 person-years in 2010-2013), primarily related to increases in papillary thyroid cancer (annual percent change, 4.4% [95% CI, 4.0%-4.7%]). Papillary thyroid cancer incidence increased for all SEER stages at diagnosis (4.6% per year for localized, 4.3% per year for regional, 2.4% per year for distant, 1.8% per year for unknown). During 1994-2013, incidence-based mortality increased 1.1% per year (95% CI, 0.6%-1.6%) (from 0.40 per 100 000 person-years in 1994-1997 to 0.46 per 100 000 person-years in 2010-2013) overall and 2.9% per year (95% CI, 1.1%-4.7%) for SEER distant stage papillary thyroid cancer. Conclusions and Relevance: Among patients in the United States diagnosed with thyroid cancer from 1974-2013, the overall incidence of thyroid cancer increased 3% annually, with increases in the incidence rate and thyroid cancer mortality rate for advanced-stage papillary thyroid cancer. These findings are consistent with a true increase in the occurrence of thyroid cancer in the United States.

IMPORTANCE: Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. OBJECTIVE: To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. DESIGN, SETTING, AND PARTICIPANTS: We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. EXPOSURES: Leisure-time physical activity of a moderate to vigorous intensity. MAIN OUTCOMES AND MEASURES: Incident cancer during follow-up. RESULTS: A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. CONCLUSIONS AND RELEVANCE: Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.

BACKGROUND: Age-period-cohort (APC) analysis can inform registry-based studies of cancer incidence and mortality, but concerns about statistical identifiability and interpretability, as well as the learning curves of statistical software packages, have limited its uptake. METHODS: We implemented a panel of easy-to-interpret estimable APC functions and corresponding Wald tests in R code that can be accessed through a user-friendly Web tool. RESULTS: Input data for the Web tool consist of age-specific numbers of events and person-years over time, in the form of a rate matrix of paired columns. Output functions include model-based estimators of cross-sectional and longitudinal age-specific rates, period and cohort rate ratios that incorporate the overall annual percentage change (net drift), and estimators of the age-specific annual percentage change (local drifts). The Web tool includes built-in examples for teaching and demonstration. User data can be input from a Microsoft Excel worksheet or by uploading a comma-separated-value file. Model outputs can be saved in a variety of formats, including R and Excel. CONCLUSIONS: APC methodology can now be carried out through a freely available user-friendly Web tool. The tool can be accessed at http://analysistools.nci.nih.gov/apc/. IMPACT: The Web tool can help cancer surveillance researchers make important discoveries about emerging cancer trends and patterns.

IMPORTANCE: An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention. OBJECTIVE: To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors. DESIGN, SETTING, AND PARTICIPANTS: Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality. EXPOSURES: Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors. MAIN OUTCOMES AND MEASURES: Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking). RESULTS: The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population. CONCLUSIONS AND RELEVANCE: This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation.

Although preservation of the spleen following abdominal trauma and spleen-preserving surgical procedures have become gold standards, about 22,000 splenectomies are still conducted annually in the USA. Infections, mostly by encapsulated organisms, are the most well-known complications following splenectomy. Recently, thrombosis and cancer have become recognized as potential adverse outcomes post-splenectomy. Among more than 4 million hospitalized USA veterans, we assessed incidence and mortality due to infections, thromboembolism, and cancer including 8,149 cancer-free veterans who underwent splenectomy with a follow-up of up to 27 years. Relative risk estimates and 95% confidence intervals were calculated using time-dependent Poisson regression methods for cohort data. Splenectomized patients had an increased risk of being hospitalized for pneumonia, meningitis, and septicemia (rate ratios=1.9-3.4); deep venous thrombosis and pulmonary embolism (rate ratios=2.2); certain solid tumors: buccal, esophagus, liver, colon, pancreas, lung, and prostate (rate ratios =1.3-1.9); and hematologic malignancies: non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and any leukemia (rate ratios =1.8-6.0). They also had an increased risk of death due to pneumonia and septicemia (rate ratios =1.6-3.0); pulmonary embolism and coronary artery disease (rate ratios =1.4-4.5); any cancer: liver, pancreas, and lung cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, and any leukemia (rate ratios =1.3-4.7). Many of the observed risks were increased more than 10 years after splenectomy. Our results underscore the importance of vaccination, surveillance, and thromboprophylaxis after splenectomy.