Cancer trends in young adults, often under 50 years, reflect recent changes in carcinogenic exposures, which could foreshadow the future overall disease burden. Previous studies reported an increase ...in early onset colorectal cancer, which could partly reflect the obesity epidemic. We examined age-specific contemporary incidence trends in the USA for 30 common cancers, including 12 obesity-related cancers.
We obtained incidence data for invasive cancers among people aged 25–84 years diagnosed from Jan 1, 1995, to Dec 31, 2014, for 25 population-based state registries in the USA. All patients in the registry were included in the analyses. We considered the 20 most common cancer types and 12 obesity-related cancers (30 cancer types in total). We used age-period-cohort modelling to estimate average annual percentage change in incidence rates by 5-year age group (25–29 years to 80–84 years in 5-year increments) and incidence rate ratios (IRR) by birth cohort (10-year overlapping birth cohorts from 1910–19 to 1980–89 in 5-year increments). No exclusion criteria were applied after including all invasive cancer cases based on age group and diagnosis year.
From 1995 to 2014 there were 14 672 409 incident cases for 30 types of cancer. Incidence significantly increased for six of 12 obesity-related cancers (multiple myeloma, colorectal, uterine corpus, gallbladder, kidney, and pancreatic cancer) in young adults (25–49 years) with steeper rises in successively younger generations. Annual increases ranged from 1·44% (95% CI −0·60 to 3·53) for multiple myeloma to 6·23% (5·32–7·14) for kidney cancer at age 25–29 years, and ranged from 0·37% (0·03–0·72) for uterine corpus cancer to 2·95% (2·74–3·16) for kidney cancer at age 45–49 years. Compared with people born around 1950, IRRs for those born around 1985 ranged from 1·59 (95% CI 1·14–2·21) for multiple myeloma to 4·91 (4·27–5·65) for kidney cancer. Conversely, incidence in young adults increased in successively younger generations for only two cancers (gastric non-cardia cancer and leukaemia), and decreased for eight of the 18 additional cancers, including smoking and HIV infection-associated cancers.
The risk of developing an obesity-related cancer seems to be increasing in a stepwise manner in successively younger birth cohorts in the USA. Further studies are needed to elucidate exposures responsible for these emerging trends, including excess bodyweight and other risk factors.
Intramural Research Department of the American Cancer Society and the Intramural Research Program of the National Cancer Institute.
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.
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.
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.
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/.
The Web tool can help cancer surveillance researchers make important discoveries about emerging cancer trends and patterns.
The National Cancer Institute Inherited Bone Marrow Failure Syndromes Cohort enrolls patients with the four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and ...Shwachman-Diamond syndrome, and follows them with a common comprehensive protocol. The current analysis includes more than double the numbers of patients and person-years since our first report, published in 2010. Patients with Fanconi anemia and dyskeratosis congenita developed head and neck and anogenital squamous cell carcinomas at rates that were hundreds-fold greater than those of the general population. In competing risk analyses the cumulative incidence of severe bone marrow failure, leading to stem cell transplantation or death, was more than 70% by age 60. Patients with Diamond-Blackfan anemia developed lung, colon, and cervical cancer at rates greater than those of the general population. The cumulative incidence of severe bone marrow failure in those with Diamond-Blackfan anemia was 50% by age 60. The smaller group, with Shwachman-Diamond syndrome, have not as yet developed a significant number of solid tumors, but 40% developed bone marrow failure by age 50. The risk of solid tumors following stem cell transplantation in Fanconi anemia and in dyskeratosis congenita was significantly higher than in non-transplanted patients. There was no clear association of genotype with cancer in any of the syndromes. Cancer was most common in Fanconi anemia, followed by dyskeratosis congenita; Diamond-Blackfan anemia and Shwachman-Diamond syndrome are less cancer-prone, but nonetheless all patients are at increased risks of bone marrow failure and specific cancers.
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Hepatocellular carcinoma (HCC) incidence rates have been increasing in the United States for the past 35 years. Because HCC has a poor prognosis, quantitative forecasts could help to inform ...prevention and treatment strategies to reduce the incidence and burden of HCC.
Single-year HCC incident case and population data for the years 2000 to 2012 and ages 35 to 84 years were obtained from the SEER 18 Registry Database. We forecast incident HCC cases through 2030, using novel age-period-cohort models and stratifying by sex, race/ethnicity, and age. Rates are presented because absolute numbers may be influenced by population increases.
Rates of HCC increased with each successive birth cohort through 1959. However, rates began to decrease with the 1960 to 1969 birth cohorts. Asians/Pacific Islanders (APIs) have had the highest HCC rates in the United States for many years, but the rates have stabilized and begun to decline in recent years. Between 2013 and 2030, rates among APIs are forecast to decline further, with estimated annual percentage changes of -1.59% among men and -2.20% among women. Thus, by 2030, Asians are forecast to have the lowest incidence rates among men, and Hispanics are forecast to have the highest rates among men (age-standardized rate, 44.2). Blacks are forecast to have the highest rate among women (age-standardized rate, 12.82).
Although liver cancer has long had some of the most rapidly increasing incidence rates, the decreasing rates seen among APIs, individuals younger than 65 years, and cohorts born after 1960 suggest that there will be declines in incidence of HCC in future years. Prevention efforts should be focused on individuals in the 1950 to 1959 birth cohorts, Hispanics, and blacks.
Human papillomavirus (HPV) has been identified as the cause of the increasing oropharyngeal cancer (OPC) incidence in some countries. To investigate whether this represents a global phenomenon, we ...evaluated incidence trends for OPCs and oral cavity cancers (OCCs) in 23 countries across four continents.
We used data from the Cancer Incidence in Five Continents database Volumes VI to IX (years 1983 to 2002). Using age-period-cohort modeling, incidence trends for OPCs were compared with those of OCCs and lung cancers to delineate the potential role of HPV vis-à-vis smoking on incidence trends. Analyses were country specific and sex specific.
OPC incidence significantly increased during 1983 to 2002 predominantly in economically developed countries. Among men, OPC incidence significantly increased in the United States, Australia, Canada, Japan, and Slovakia, despite nonsignificant or significantly decreasing incidence of OCCs. In contrast, among women, in all countries with increasing OPC incidence (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and United Kingdom), there was a concomitant increase in incidence of OCCs. Although increasing OPC incidence among men was accompanied by decreasing lung cancer incidence, increasing incidence among women was generally accompanied by increasing lung cancer incidence. The magnitude of increase in OPC incidence among men was significantly higher at younger ages (< 60 years) than older ages in the United States, Australia, Canada, Slovakia, Denmark, and United Kingdom.
OPC incidence significantly increased during 1983 to 2002 predominantly in developed countries and at younger ages. These results underscore a potential role for HPV infection on increasing OPC incidence, particularly among men.
We develop a new age-period-cohort model for cancer surveillance research; the theory and methods are broadly applicable. In the new model, cohort deviations are weighted to account for the variable ...number of periods that each cohort is observed. Weighting ensures that the fitted rates can be naturally expressed as a function of age × a function of period × a function of cohort. Furthermore, the age, period, and cohort deviations are split into orthogonal quadratic components plus higher-order terms. These decompositions enable powerful combination significance tests of first- and second-order age, period, and cohort effects. The regression parameters of the orthogonal quadratic polynomials (global curvatures) quantify how fast on average the trends in the rates are changing. Importantly, the global curvature for cohort determines the least squares slope of the expected annual percentage changes by age group versus age (local drifts), thereby providing a powerful one-degree-of-freedom test of age-period interactions. We introduce new estimable functions, including age gradients that quantify the rate of change of the longitudinal and cross-sectional age curves at each attained age, and gradient shifts that quantify how the cross-sectional age trend varies by period. We illustrate the new model using nationally representative multiple myeloma incidence. Comprehensive proofs are given in technical appendices. We provide an R package.
Abstract
Background
The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity. In recent decades, the prevalence ...rates of these two major causes declined and increased, respectively, with changes in Western lifestyles. We therefore assessed gastric cancer incidence trends for US race/ethnic groups, 1995–2013.
Methods
Age-standardized rates (ASRs) from 45 North American Association of Central Cancer Tumor Registries were summarized by estimated annual percentage change (EAPC) and 95% confidence intervals (CIs). Age period cohort models supplemented standard descriptive techniques and projected future trends.
Results
There were 137 447 noncardia cancers in 4.4 billion person-years of observation. Among non-Hispanic whites, the ASR was 2.2 per 100 000 person-years, with an EAPC of –2.3% (95% CI = –2.0% to –2.6%). Notwithstanding this overall decline, EAPCs rose 1.3% (95% CI = 0.6% to 2.1%) for persons younger than age 50 years and fell –2.6% (95% CI = –2.4% to –2.9%) for older individuals. These converging trends manifested a birth cohort effect more pronounced among women than men, with incidence among women born in 1983 twofold (95% CI = 1.1-fold to 3.6-fold) greater than those born in 1951. Age interaction was also statistically significant among Hispanic whites, with slightly increasing vs decreasing EAPCs for younger and older individuals, respectively. Incidence declined regardless of age for other races. Current trends foreshadow expected reversals in both falling incidence and male predominance among non-Hispanic whites.
Conclusions
Dysbiosis of the gastric microbiome associated with modern living conditions may be increasing risk of autoimmune gastritis and consequent noncardia cancer. The changing face by age and sex of gastric cancer warrants analytical studies to identify potential causal mechanisms.
Colorectal cancer (CRC) incidence in the United States is declining rapidly overall but, curiously, is increasing among young adults. Age-specific and birth cohort patterns can provide etiologic ...clues, but have not been recently examined.
CRC incidence trends in Surveillance, Epidemiology, and End Results areas from 1974 to 2013 (n = 490 305) were analyzed by five-year age group and birth cohort using incidence rate ratios (IRRs) and age-period-cohort modeling.
After decreasing in the previous decade, colon cancer incidence rates increased by 1.0% to 2.4% annually since the mid-1980s in adults age 20 to 39 years and by 0.5% to 1.3% since the mid-1990s in adults age 40 to 54 years; rectal cancer incidence rates have been increasing longer and faster (eg, 3.2% annually from 1974-2013 in adults age 20-29 years). In adults age 55 years and older, incidence rates generally declined since the mid-1980s for colon cancer and since 1974 for rectal cancer. From 1989-1990 to 2012-2013, rectal cancer incidence rates in adults age 50 to 54 years went from half those in adults age 55 to 59 to equivalent (24.7 vs 24.5 per 100 000 persons: IRR = 1.01, 95% confidence interval CI = 0.92 to 1.10), and the proportion of rectal cancer diagnosed in adults younger than age 55 years doubled from 14.6% (95% CI = 14.0% to 15.2%) to 29.2% (95% CI = 28.5% to 29.9%). Age-specific relative risk by birth cohort declined from circa 1890 until 1950, but continuously increased through 1990. Consequently, compared with adults born circa 1950, those born circa 1990 have double the risk of colon cancer (IRR = 2.40, 95% CI = 1.11 to 5.19) and quadruple the risk of rectal cancer (IRR = 4.32, 95% CI = 2.19 to 8.51).
Age-specific CRC risk has escalated back to the level of those born circa 1890 for contemporary birth cohorts, underscoring the need for increased awareness among clinicians and the general public, as well as etiologic research to elucidate causes for the trend. Further, as nearly one-third of rectal cancer patients are younger than age 55 years, screening initiation before age 50 years should be considered.
Human papillomavirus-positive oropharynx cancer incidence has increased rapidly in cohorts of US white men born during the 1930s to 1950s. It is unknown how the trajectory of the oropharynx cancer ...epidemic may be changing in the United States.
Using US cancer registry information, we investigated whether increases in oropharynx cancer have continued into recent birth cohorts and forecasted the future burden across age, sex, and race/ethnicity subgroups. Log-linear Joinpoint regression and age-period-cohort models were used to evaluate incidence trends during 1992 to 2015 and projections through 2029.
Among white men, oropharynx cancer incidence increased rapidly in individuals born during 1939 to 1955 (5.3% per 2-year birth cohort; 95% CI, 4.8% to 5.7%), but this rate of increase significantly moderated in individuals born during 1955 to 1969 (1.7% per 2-year birth cohort; 95% CI, 1.0% to 2.4%). Should these birth-cohort trends continue, from 2016 to 2029 we forecast that incidence will increase dramatically in older white men 65 to 74 years of age (from 40.7 to 71.2 per 100,000) and 75 to 84 years of age (from 25.7 to 50.1 per 100,000), moderately in white men 55 to 64 years of age (from 40.3 to 52.0 per 100,000), and remain stable in white men 45 to 54 years of age (approximately 18 per 100,000). Accounting for population growth, we project an increase in annual number of cases in the United States from 20,124 (95% CI, 19,779 to 20,469) in 2016 to 30,629 (95% CI, 29,413 to 31,845) in 2029, primarily driven by older individuals (age ≥ 65 years; from 7,976 95% CI, 7,782 to 8,172 to 18,072 95% CI, 17,271 to 18,895) and white men (from 14,453 95% CI, 14,142 to 14,764 to 22,241 95% CI, 21,119 to 23,364).
The exponential increase in oropharynx cancer incidence in young white US men has ebbed, and modest increases are occurring/anticipated in cohorts born after 1955. Continued strong increases in incidence in cohorts born before 1955, and an approximate 50% increase in size of the US population age 65 years or older through 2029, portend a substantial shift in burden to elderly white men.
Because of its rarity, male breast cancer is often compared with female breast cancer.
To compare and contrast male and female breast cancers, we obtained case and population data from the National ...Cancer Institute's Surveillance, Epidemiology, and End Results program for breast cancers diagnosed from 1973 through 2005. Standard descriptive epidemiology was supplemented with age-period-cohort models and breast cancer survival analyses.
Of all breast cancers, men with breast cancer make up less than 1%. Male compared with female breast cancers occurred later in life with higher stage, lower grade, and more estrogen receptor-positive tumors. Recent breast cancer incidence and mortality rates declined over time for men and women, but these trends were greater for women than for men. Comparing patients diagnosed from 1996 through 2005 versus 1976 through 1985, and adjusting for age, stage, and grade, cause-specific hazard rates for breast cancer death declined by 28% among men (P = .03) and by 42% among women (P approximately 0).
There were three intriguing results. Age-specific incidence patterns showed that the biology of male breast cancer resembled that of late-onset female breast cancer. Similar breast cancer incidence trends among men and women suggested that there are common breast cancer risk factors that affect both sexes, especially estrogen receptor-positive breast cancer. Finally, breast cancer mortality and survival rates have improved significantly over time for both male and female breast cancer, but progress for men has lagged behind that for women.
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