Incidence of Burkitt lymphoma in the United States during 2000 to 2019.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that occurs worldwide. A study of BL in the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program during 1973 to 2005 (n = 3043) revealed three age-specific incidence peaks of BL and rates that were rising. We studied BL cases diagnosed in SEER 22 during 2000 to 2019 (n = 11 626) to investigate age-specific BL incidence rates and temporal trends. The age-standardized BL incidence rate was 3.96/million person-years, with a 2.85:1 male-to-female ratio. The BL rate among both Hispanic and White individuals was higher than in Black individuals (4.52, 4.12 vs 3.14). Age-specific BL rates showed peaks during pediatric, adult and elderly years in males and pediatric and elderly peaks in females. Based on 4524 BL cases with HIV status (SEER 13), only one peak in adult males (45 years) was observed. Overall age-standardized BL incidence rates rose 1.2%/year (not significant) up to 2009 then fell significantly by 2.4%/year thereafter. Temporal trends in BL rates during 2000 to 2019 varied with age group as pediatric BL rates rose 1.1%/year, while elderly BL rates fell 1.7%/year and adult BL rates rose 3.4%/year until 2007 before falling 3.1%/year thereafter. Overall survival from BL was 64% at 2 years, being highest in pediatric patients and lowest in Black and elderly individuals vs other subgroups. Survival improved by 20% between 2000 and 2019. Our data suggest that BL age-specific incidence rates are multimodal and that overall BL rates rose up to 2009 and then fell, suggesting changes in etiological factors or diagnosis.

Body Composition and Metabolomics in the Alberta Physical Activity and Breast Cancer Prevention Trial.

BACKGROUND: Obesity is correlated with many biomarkers, but the extent to which these correlate with underlying body composition is poorly understood. OBJECTIVES: Our objectives were to 1) describe/compare distinct contributions of fat/lean mass with BMI-metabolite correlations and 2) identify novel metabolite biomarkers of fat/lean mass. METHODS: The Alberta Physical Activity and Breast Cancer Prevention Trial was a 2-center randomized trial of healthy, inactive, postmenopausal women (n = 304). BMI (in kg/m2) was calculated using weight and height, whereas DXA estimated fat/lean mass. Ultra-performance liquid chromatography and mass spectrometry measured relative concentrations of serum metabolite concentrations. We estimated partial Pearson correlations between 1052 metabolites and BMI, adjusting for age, smoking, and site. Fat mass index (FMI; kg/m2) and lean mass index (LMI; kg/m2) correlations were estimated similarly, with mutual adjustment to evaluate independent effects. RESULTS: Using a Bonferroni-corrected α level <4.75 × 10-5,  we observed 53 BMI-correlated metabolites (|r| = 0.24-0.42). Of those, 21 were robustly correlated with FMI (|r| > 0.20), 25 modestly (0.10 ≤ |r| ≤ 0.20), and 7 virtually null (|r| < 0.10). Ten of 53 were more strongly correlated with LMI than with FMI. Examining non-BMI-correlated metabolites, 6 robustly correlated with FMI (|r| = 0.24-0.31) and 2 with LMI (r = 0.25-0.26). For these, correlations for fat and lean mass were in opposing directions compared with BMI-correlated metabolites, in which correlations were mostly in the same direction. CONCLUSIONS: Our results demonstrate how a thorough evaluation of the components of fat and lean mass, along with BMI, provides a more accurate assessment of the associations between body composition and metabolites than BMI alone. Such an assessment makes evident that some metabolites correlated with BMI predominantly reflect lean mass rather than fat, and some metabolites related to body composition are not correlated with BMI. Correctly characterizing these relations is important for an accurate understanding of how and why obesity is associated with disease.

Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts.

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. SIGNIFICANCE: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.

iCARE: An R package to build, validate and apply absolute risk models.

This report describes an R package, called the Individualized Coherent Absolute Risk Estimator (iCARE) tool, that allows researchers to build and evaluate models for absolute risk and apply them to estimate an individual's risk of developing disease during a specified time interval based on a set of user defined input parameters. An attractive feature of the software is that it gives users flexibility to update models rapidly based on new knowledge on risk factors and tailor models to different populations by specifying three input arguments: a model for relative risk, an age-specific disease incidence rate and the distribution of risk factors for the population of interest. The tool can handle missing information on risk factors for individuals for whom risks are to be predicted using a coherent approach where all estimates are derived from a single model after appropriate model averaging. The software allows single nucleotide polymorphisms (SNPs) to be incorporated into the model using published odds ratios and allele frequencies. The validation component of the software implements the methods for evaluation of model calibration, discrimination and risk-stratification based on independent validation datasets. We provide an illustration of the utility of iCARE for building, validating and applying absolute risk models using breast cancer as an example.

Identifying potential targets for prevention and treatment of amyotrophic lateral sclerosis based on a screen of medicare prescription drugs.

Background: Few well-established factors are associated with risk of amyotrophic lateral sclerosis (ALS). We comprehensively evaluate prescription drugs use in administrative health claims from U.S. Medicare beneficiaries in relation to ALS risk to generate hypotheses for further research. Methods: This is a population-based case-control study of 10,450 U.S. Medicare participants (ages 66-89 years) diagnosed with ALS, based on Medicare Parts A and B fee-for-service claims, between 1 January 2008, and 31 December 2014, and 104,500 controls (1:10 ratio) frequency-matched on age, sex, and selection year. Odds ratios (ORs) for the ALS association with 685 prescription drugs were estimated using logistic regression models for both a one- and three-year lag period. Covariates included demographic characteristics and key comorbidities, among other factors. Prescription drug use was based on Medicare Part D claims. We adjusted for multiple comparisons using a Bonferroni correction. Additional a priori analyses of sex hormone drugs were also undertaken. Results: In the large drug screen, we found 10 drugs significantly associated with lower ALS risk after the multiple-testing correction in a one-year and three-year lag analysis. These included several drugs for hypertension, diabetes, and cardiovascular disease. In a separate a priori inquiry of sex hormone drugs, tamoxifen was related to lower ALS risk, and testosterone to a higher risk in women. Conclusions: These associations warrant replication in databases that include information on the severity and duration of medical conditions underlying drug use, and drug use over a longer portion of individuals' lifespans, to further help evaluate confounding by indication.

Trends in Major Gastrectomy for Cancer: Frequency and Outcomes.

BACKGROUND: Declining incidence of gastric cancer in the USA has presumably resulted in lower rates of major gastrectomy for cancer. The impact on perioperative outcomes remains undefined. The aims of this study were to characterize national trends in frequency of major gastrectomy for cancer, identify factors associated with in-hospital mortality, and examine outcome disparities by race/ethnicity. METHODS: Nationwide inpatient sample data from 1993 to 2013 were queried for procedural and diagnostic codes (ICD-9) relating to total and partial gastrectomy procedures. Gastric resections for cancer were compared to those for peptic ulcer disease for reference. Patient demographics, comorbidity score, mortality, and hospital characteristics were recorded as covariates. RESULTS: A significant decrease in annual rates of partial and total gastrectomy was observed from 1993 to 2013 (p < 0.0001). The change in absolute number and percent decline was greater for partial gastrectomy (- 39.3%) than total gastrectomy (- 19%). There was a 34.0% decrease in gastrectomy for cancer in Whites and a 61.2% increase among Hispanic patients over two decades. In-hospital mortality also significantly decreased over the study period (7.7% to 2.7%). Factors associated with lower mortality rates included male sex and treatment at urban teaching hospitals. Analysis of trends revealed that gastrectomy for cancer was performed with increasing frequency at urban teaching hospitals. CONCLUSIONS: The frequency of major gastric resections in the USA has declined over two decades. Overall, in-hospital mortality rates also have decreased significantly. Declining in-hospital mortality after gastrectomy for cancer is associated with more frequent treatment at urban teaching hospitals.

Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013.

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.

Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer.

Background: In a European cohort, it was previously reported that 35% of oropharyngeal cancer (OPC) patients were human papillomavirus type-16 (HPV16) seropositive up to 10 years before diagnosis vs 0.6% of cancer-free controls. Here, we describe the kinetics of HPV16-E6 antibodies prior to OPC diagnosis. Methods: We used annual serial prediagnostic blood samples from the PLCO Cancer Screening Trial. Antibodies to HPV were initially assessed in prediagnostic blood drawn at study enrollment from 198 incident head and neck cancer patients (median years to cancer diagnosis = 6.6) and 924 matched control subjects using multiplex serology, and subsequently in serial samples (median = 5/individual). Available tumor samples were identified and tested for HPV16 RNA to define HPV-driven OPC. Results: HPV16-E6 antibodies were present at baseline in 42.3% of 52 OPC patients and 0.5% of 924 control subjects. HPV16-E6 antibody levels were highly elevated and stable across serial blood samples for 21 OPC patients who were seropositive at baseline, as well as for one OPC patient who seroconverted closer to diagnosis. All five subjects with HPV16-driven OPC tumors were HPV16-E6-seropositive, and the four subjects with HPV16-negative OPC tumors were seronegative. The estimated 10-year cumulative risk of OPC was 6.2% (95% confidence interval [CI] = 1.8% to 21.5%) for HPV16-E6-seropositive men, 1.3% (95% CI = 0.1% to 15.3%) for HPV16-E6-seropositive women, and 0.04% (95% CI = 0.03% to 0.06%) among HPV16-E6-seronegative individuals. Conclusions: Forty-two percent of subjects diagnosed with OPC between 1994 and 2009 in a US cohort were HPV16-E6 seropositive, with stable antibody levels during annual follow-up for up to 13 years prior to diagnosis. Tumor analysis indicated that the sensitivity and specificity of HPV16-E6 antibodies were exceptionally high in predicting HPV-driven OPC.

Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults.

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.

Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States.

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.

Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001-12.

Descriptive epidemiological information on myeloproliferative neoplasms (MPNs) and myelodysplastic (MDS)/MPNs is largely derived from single institution and European population-based studies. Data obtained following adoption of the World Health Organization classification of haematopoietic neoplasms and JAK2 V617F mutation testing are sparse. Using population-based data, we comprehensively assessed subtype-specific MPN and MDS/MPN incidence rates (IRs), IR ratios (IRRs) and relative survival (RS) in the United States (2001-12). IRs were highest for polycythaemia vera (PV) (IR = 10·9) and essential thrombocythaemia (ET) (IR = 9·6). Except for ET and mastocytosis, overall IRs were significantly higher among males (IRRs = 1·4-2·3). All evaluable MPNs were associated with lower IRs among Hispanic whites than non-Hispanic whites (NHWs), with the exception of BCR-ABL1-positive chronic myeloid leukaemia (CML), chronic eosinophilic leukaemia (CEL) and juvenile myelomonocytic leukaemia. Except for CEL, Asians/Pacific Islanders had significantly lower MPN IRs than NHWs. ET, MPN-unclassifiable and CEL IRs were 18%, 19% and 60% higher, respectively, among blacks than NHWs. Five-year RS was more favourable for younger (<60 years) than older individuals and for women compared with men, except for PV at older ages. RS was highest (>90%) for younger PV and ET patients and lowest (<20%) for older chronic myelomonocytic leukaemia and atypical BCR-ABL1-negative CML patients. Varying MPN and MDS/MPN incidence patterns by subtype support distinct aetiologies and/or susceptible populations. Decreased survival rates as compared to that expected in the general population were associated with every MPN subtype, highlighting the need for new treatments, particularly among older individuals.

International long-term trends and recent patterns in the incidence of leukemias and lymphomas among children and adolescents ages 0-19 years.

To enhance understanding of etiology, we examined international population-based cancer incidence data for lymphoid leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma and myeloid leukemia among children aged 0-19. Based on temporal trends during 1978-2007 in 24 populations, lymphoid leukemia and myeloid leukemia incidence rates generally have not changed greatly and differences in rates for non-Hodgkin and for Hodgkin lymphoma have diminished in some regions. Lymphoid leukemia rates during 2003-2007 in 54 populations varied about 10-fold, with rates highest in US white Hispanics (50.2 per million person-years) and Ecuador (48.3) and lowest in US blacks (20.4), Tunisia (17.7) and Uganda (6.9). Non-Hodgkin lymphoma rates varied 30-fold, with very high rates in sub-Saharan Africa (146.0 in Malawi and 54.3 in Uganda) and low rates (≤ 10) in some Asian populations (China, Japan, India, the Philippines and Thailand) and U.S. Asian-Pacific Islanders, eastern and northern European populations and Puerto Rico. Hodgkin lymphoma rates varied 15-fold, with rates highest in Italy (21.3) and lowest in China (1.7). Myeloid leukemia rates varied only about fivefold, with rates highest in the Philippines and Korea (exceeding 14.0) and lowest in Eastern Europe (5.9 in Serbia and 5.3 in the Czech Republic) and Uganda (2.7). The boy/girl average incidence rate ratios were 2.00 or lower. Age-specific patterns differed among the four hematopoietic malignancies, but were generally consistent within major categories world-wide, except for non-Hodgkin lymphoma. A systematic world-wide approach comparing postulated etiologic factors in low- versus high-risk populations may help clarify the etiology of these childhood malignancies.

Prostate cancer incidence in 43 populations worldwide: An analysis of time trends overall and by age group.

Prostate cancer is a significant public health burden and a major cause of morbidity and mortality among men worldwide. Analyzing geographic patterns and temporal trends may help identify high-risk populations, suggest the degree of PSA testing, and provide clues to etiology. We used incidence data available from the International Agency for Research on Cancer (IARC) and certain cancer registries for 43 populations across five continents during a median period of 24 years. Trends in overall prostate cancer rates showed five distinct patterns ranging from generally monotonic increases to peaking of rates followed by declines, which coincide somewhat with changes in the prevalence of PSA testing. Trends in age-specific rates generally mirrored those in the overall rates, with several notable exceptions. For populations where overall rates increased rapidly and then peaked, exemplified in North America and Oceania, the highest incidence tended to be most pronounced and occurred during earlier calendar years among older men compared with younger ones. For populations with almost continual increases in overall rates, exemplified in Eastern Europe and Asia, peaks were evident among men aged ≥ 75 years in many instances. Rates for ages 45-54 years did not clearly stabilize or decline in the majority of studied populations. Global geographic variation remained substantial for both overall and age-specific incidence rates regardless of levels of PSA testing, with the lowest rates consistently in Asia. Explanations for the persistent geographic differences and the continuing increases of especially early-onset prostate cancer remain unclear.

US lung cancer trends by histologic type.

BACKGROUND: Lung cancer incidence rates overall are declining in the United States. This study investigated the trends by histologic type and demographic characteristics. METHODS: Surveillance, Epidemiology, and End Results (SEER) program rates of microscopically confirmed lung cancer overall and squamous cell, small cell, adenocarcinoma, large cell, other, and unspecified carcinomas among US whites and blacks diagnosed from 1977 to 2010 and white non-Hispanics, Asian/Pacific Islanders, and white Hispanics diagnosed from 1992 to 2010 were analyzed by sex and age. RESULTS: Squamous and small cell carcinoma rates declined since the 1990s, although less rapidly among females than males. Adenocarcinoma rates decreased among males and only through 2005, after which they then rose during 2006 to 2010 among every racial/ethnic/sex group; rates for unspecified type declined. Male/female rate ratios declined among whites and blacks more than among other groups. Recent rates among young females were higher than among males for adenocarcinoma among all racial/ethnic groups and for other specified carcinomas among whites. CONCLUSIONS: US lung cancer trends vary by sex, histologic type, racial/ethnic group, and age, reflecting historical cigarette smoking rates, duration, cessation, cigarette composition, and exposure to other carcinogens. Substantial excesses among males have diminished and higher rates of adenocarcinoma among young females have emerged as rates among males declined more rapidly. The recognition of EGFR mutation and ALK rearrangements that occur primarily in adenocarcinomas are the primary basis for the molecular revolution that has transformed lung cancer diagnosis and treatment over the past decade, and these changes have affected recent type-specific trends.

A web tool for age-period-cohort analysis of cancer incidence and mortality rates.

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.

Incidence of marginal zone lymphoma in the United States, 2001-2009 with a focus on primary anatomic site.

The aetiology of marginal zone lymphoma (MZL) is purported to differ by anatomic site. While this is supported by clinical series of single MZL sites, no population-based study has comprehensively assessed incidence patterns across sites. To gain insight into disease aetiology, we assessed MZL incidence by site using data from 18 U.S. Surveillance, Epidemiology and End Results (SEER) Program population-based registries. We calculated age-adjusted incidence rates (IRs) by sex, race, and calendar year. During 2001-2009, 4,081 (IR = 5·7/1,000,000 person-years) and 8,821 (IR = 12·3) individuals were diagnosed with nodal MZL and extranodal MZL, respectively. The most common extranodal sites were stomach (IR = 3·8), spleen (IR = 1·6), eye/adnexa (IR = 1·4), and lung, skin, and salivary glands (IRs = 0·9-1·0). We observed distinct age-specific patterns by MZL site, with IRs increasing steeply at younger ages and less prominently after mid-life at several sites, except skin. Gender and racial/ethnic disparities were also apparent across sites. Between 2001-2005 and 2006-2009, MZL IRs decreased significantly for gastric (-15%) and soft tissue (-28%) sites, whereas IRs increased significantly for lung (18%), skin (43%), and kidney/renal pelvis (116%). In combination, our findings support the contention that MZL is characterized by aetiological heterogeneity across sites and susceptibility is probably influenced by intrinsic characteristics and environmental exposures.

Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up.

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.

Mood disorders and risk of lung cancer in the EAGLE case-control study and in the U.S. Veterans Affairs inpatient cohort.

BACKGROUND: Mood disorders may affect lung cancer risk. We evaluated this hypothesis in two large studies. METHODOLOGY/PRINCIPAL FINDINGS: We examined 1,939 lung cancer cases and 2,102 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study conducted in Italy (2002-2005), and 82,945 inpatients with a lung cancer diagnosis and 3,586,299 person-years without a lung cancer diagnosis in the U.S. Veterans Affairs Inpatient Cohort (VA study), composed of veterans with a VA hospital admission (1969-1996). In EAGLE, we calculated odds ratios (ORs) and 95% confidence intervals (CI), with extensive adjustment for tobacco smoking and multiple lifestyle factors. In the VA study, we estimated lung cancer relative risks (RRs) and 95% CIs with time-dependent Poisson regression, adjusting for attained age, calendar year, hospital visits, time within the study, and related previous medical diagnoses. In EAGLE, we found decreased lung cancer risk in subjects with a personal history of mood disorders (OR: 0.59, 95% CI: 0.44-0.79, based on 121 lung cancer incident cases and 192 controls) and family history of mood disorders (OR: 0.62, 95% CI: 0.50-0.77, based on 223 lung cancer cases and 345 controls). The VA study analyses yielded similar results (RR: 0.74, 95% CI: 0.71-0.77, based on 2,304 incident lung cancer cases and 177,267 non-cancer person-years) in men with discharge diagnoses for mood disorders. History of mood disorders was associated with nicotine dependence, alcohol and substance use and psychometric scales of depressive and anxiety symptoms in controls for these studies. CONCLUSIONS/SIGNIFICANCE: The consistent finding of a relationship between mood disorders and lung cancer risk across two large studies calls for further research into the complex interplay of risk factors associated with these two widespread and debilitating diseases. Although we adjusted for smoking effects in EAGLE, residual confounding of the results by smoking cannot be ruled out.

Cigarette smoking, alcohol intake, and thyroid cancer risk: a pooled analysis of five prospective studies in the United States.

OBJECTIVE: We examined the associations between cigarette smoking, alcohol intake, and thyroid cancer risk in a pooled analysis of five prospective studies. METHODS: Data from five prospective U.S. studies were standardized and then combined into one aggregate dataset (384,433 men and 361,664 women). Pooled hazard ratios (HR) and 95 % confidence intervals (CI) for thyroid cancer were estimated from mutually adjusted models of cigarette smoking and alcohol intake, which were additionally adjusted for age, sex, education, race, marital status, body mass index, and cohort. RESULTS: Over follow-up, 1,003 incident thyroid cancer cases (335 men and 668 women) were identified. Compared to never smokers, current smoking was associated with reduced risk of thyroid cancer (HR = 0.68, 95 % CI 0.55-0.85); this association was slightly stronger among non-drinkers (HR = 0.46, 95 % CI 0.29-0.74). No reduction in risk was observed for former, compared to never, smokers. Greater smoking intensity, duration, and pack-years were associated with further reductions in risk among former and current smokers. Alcohol intake was also inversely associated with thyroid cancer risk (≥7 drinks/week versus 0, HR = 0.72, 95 % CI 0.58-0.90, p trend = 0.002). Inverse associations with smoking and alcohol were more pronounced for papillary versus follicular tumors. CONCLUSION: The results of this pooled analysis suggest that both cigarette smoking and alcohol consumption are associated with reduced risks of papillary thyroid cancer and, possibly, follicular thyroid cancer.

Oral cavity and pharynx cancer incidence trends by subsite in the United States: changing gender patterns.

Objective. To evaluate oral cavity and pharynx cancer (OCPC) patterns by gender. Methods. We used Surveillance, Epidemiology, and End Results program data for 71,446 cases diagnosed during 1975-2008 to classify OCPC by anatomic subsite as potentially HPV-related or not, with oral tongue cancer considered a separate category. Results. Total OCPC rates among men were 2-4 times those among women. Among whites, total OCPC rates rose in the younger age groups due to substantial increases in successive birth cohorts for HPV-related cancers, more rapid among men than women, and oral tongue cancers, more rapid among women than men. Among blacks, total OCPC rates declined among cohorts born since 1930 reflecting the strong downward trends for HPV-unrelated sites. Among Hispanics and Asians, HPV-unrelated cancer rates generally declined, and oral tongue cancer rates appeared to be converging among young men and women. Conclusions. Decreases in total OCPC incidence reflect reductions in smoking and alcohol drinking. Rising HPV-related cancers among white men may reflect changing sexual practices. Reasons for the increasing young oral tongue cancer rates are unknown, but the narrowing of the gender differences provides a clue.