Time series analysis supporting the hypothesis that enhanced cosmic radiation during germ cell formation can increase breast cancer mortality in germ cell cohorts

 Techniques from cancer epidemiology and time series analysis were used to explore the hypothesis that cosmic radiation can induce germ cell changes leading to increases in future breast cancer mortality. A birth cohort time series for female breast cancer mortality was obtained using a model-independent, age-period-cohort analysis on age-specific mortality data for 1940–1990. The birth cohort series contained several oscillatory components, which were isolated and compared to the corresponding frequency components of a cosmic ray surrogate time series – Greenland ice-core ¹⁰Be concentrations. A technique, referred to as component wave-train alignment, was used to show that the breast cancer and cosmic ray oscillations were phase-locked approx. 25 years before the time of birth. This is consistent with the time of germ cell formation, which occurs during the fetal development stage of the preceding generation. Evidence is presented that the observable oscillations in the birth cohort series were residues of oscillations of much larger amplitude in the germ cell cohort, which were attenuated by the effect of the broad maternal age distribution. It is predicted that a minimum of 50% of breast cancer risk is associated with germ cell damage by cosmic radiation (priming event), which leads to the development of individuals with a higher risk of breast cancer. It is proposed that the priming event, by preceding other steps of carcinogenesis, works in concert with risk factor exposure during life. The priming event is consistent with epigenetic changes such as imprinting. Received: 10 June 1996 / Revised: 4 December 1996 / Accepted: 19 December 1996     

Secular trends in incidence and mortality of bladder cancer in China, 1990–2017: A joinpoint and age-period-cohort analysis

BackgroundBladder cancer is closely related to occupational carcinogens, and China is undergoing a rapid industrialization. However, trend of bladder cancer incidence and mortality remains unknown in China.MethodsIncidence and mortality rates of bladder cancer (1990–2017) were collected for each 5-year age group stratified by gender (males/females) from the Global Burden of Disease (GBD) 2017 study. The average annual percentage change (AAPC) of rates were analyzed by joinpoint regression analysis; age, period and cohort effects on incidence and mortality were simultaneously estimated by age-period-cohort model.ResultsThrough 1990–2017, age-standardized incidence rates significantly rose in men (AAPC = 0.72%, 95% CI: 0.5%, 0.9%) while decreased in women (-1.25%: -1.6%, -0.9%); age-standardized mortality rates decreased in both men (-1.09%: -1.2%, -0.9%) and women (-2.48%: -2.8%, -2.2%). The joinpoint regression analysis showed the mortality almost decreased in all age groups; while the incidence increased in men for older age groups (from 45 to 49 to 80–84). Moreover, age effect showed the incidence and mortality increased with age; the incidence and mortality increased with time period, while in women period effect stop decreasing and began to increase since 2007; cohort effect showed them decreased with birth cohorts.ConclusionsThe incidence of bladder cancer is increasing in men but mortality decreases in both sexes. Both the incidence and mortality in men substantially increase with age and period, while the rates in women increased with period since 2007. The period effect may indicate the increased risks to bladder cancer in Chinese men. Etiological studies are needed to identify the factors driving these trends of bladder cancer.     

Increased incidence of colon cancer among individuals younger than 50 years: A 17 years analysis from the cancer registry of the municipality of Milan,Italy

BackgroundColorectal cancer (CRC) overall incidence has been decreasing in the last decade. However, there is evidence of an increasing frequency of early-onset CRC in young individuals in several countries. The aim of this study is to evaluate the trends of CRC occurrence over 17 years in the municipality of Milan, Italy, focusing on early-onset CRC.Population and methodsThis retrospective study was performed using the Cancer Registry of the municipality of Milan, including all cases of CRC diagnosed 1999-2015. Incidence rates were stratified by age and anatomic subsite, and trends over time were measured using the estimated annual percentage change. Age-period-cohort modelling was used to disentangle the different effects.Results18,783 cases of CRC were included. CRC incidence rates among individuals aged 50–60 years declined annually by 3% both in colon and in rectal cancer. Conversely, in adults younger than 50 years, overall CRC occurrence increased annually by 0.7%, with a diverging trend for colon (+2.6%) and rectal (−5.3%) cancer. Among individuals aged 60 years and older, CRC incidence rates increased by 1.0% annually up to 2007, and decrease thereafter by 4% per year, both for colon and rectal cancer. Age-period-cohort models showed a reduction of CRC risk for the cohorts born up to 1979, followed by an increase in younger cohorts. In contrast, rectal cancer among women showed a systematic risk decrease for all birth cohorts.ConclusionsThe study highlights increasing incidence of colon cancer in younger subjects and a decrease in incidence rates for rectal cancer in females.     

Escalating burden of breast cancer in southern Thailand: Analysis of 1990–2010 incidence and prediction of future trends

BackgroundThailand is undergoing an epidemiologic transition, with decreasing incidence of infectious diseases and increasing rates of chronic conditions, including cancer. Breast cancer has the highest incidence rates among females both in the southern region Thailand and throughout Thailand. However, there is a lack of research on the epidemiology of this and other cancers.MethodsHere we use cancer incidence data from the Songkhla Cancer Registry to characterize and analyze the incidence of breast cancer in Southern Thailand. We use joinpoint analysis, age-period-cohort models and nordpred analysis to investigate the incidence of breast cancer in Southern Thailand from 1990 to 2010 and project future trends from 2010 to 2029.ResultsWe found that age-adjusted breast cancer incidence rates in Southern Thailand increased by almost 300% from 1990 to 2010 going from 10.0 to 27.8 cases per 100,000 person-years. Both period and cohort effects played a role in shaping the increase in incidence. Three distinct incidence projection methods consistently suggested that incidence rates will continue to increase in the future with incidence for women age 50 and above increasing at a higher rate than for women below 50.ConclusionsTo date, this is the first study to examine Thai breast cancer incidence from a regional registry. This study provides a basis for future planning strategies in breast cancer prevention and to guide hypotheses for population-based epidemiologic research in Thailand.     

Forecasting with the age-period-cohort model and the extended chain-ladder model

We consider forecasting from age-period-cohort models, as wellas from the extended chain-ladder model. The parameters of thesemodels are known only to be identified up to linear trends.Forecasts from such models may therefore depend on arbitrarylinear trends. A condition for invariant forecasts is proposed.A number of standard forecast models are analysed.     

The impact of skin cancer prevention efforts in New South Wales,Australia: Generational trends in melanoma incidence and mortality

BackgroundIn Australia, skin cancer awareness campaigns have focused on raising the awareness and consequences of skin cancer and highlighting the importance of utilising sun protection.MethodsTrends in melanoma incidence and mortality have been explored elsewhere in Australia and this study sought to examine the trends in NSW. Anonymised incidence and mortality data for in situ and invasive melanoma from 1988 to 2014 were obtained from the NSW Cancer Registry. Trends of melanoma incidence and mortality were analysed using segmented regression to allow for changes over time. Birth cohort patterns were assessed using age–period–cohort models.ResultsOver the period, incidence of in situ melanoma increased in all age groups although the rates were lowest in those under 40 years of age. Incidence of invasive melanoma was either stable or decreased in people under 60, while it increased in those aged 60 and above, particularly in men. Age–period–cohort analysis revealed decreasing age-specific incidence of invasive melanoma under 40 years of age. Melanoma mortality over the period was stable or decreased in all groups except in men aged 60 or over. Overall, mortality rates generally declined or remained stable particularly in recent years.ConclusionIt is encouraging that rates of invasive melanoma are declining in the younger age cohorts – which could be attributed to both primary prevention efforts with individuals protecting their skin as well as early detection through self assessment and clinician performed skin checks. In addition, whilst it is important to monitor the increasing rates of in situ melanoma, the increase is likely due to early detection and treatment of melanoma that could have progressed to invasive melanoma and therefore detection whilst still in situ is an improved outcome. Overall, the results demonstrate the need to continue to improve the understanding of and compliance with primary skin cancer prevention measures in order to reduce population UVR exposure and overall melanoma incidence.     

A population-based age-period-cohort study of colorectal cancer incidence comparing Asia against the West

BackgroundColorectal cancer (CRC) is the third most common cancer worldwide but incidence varied widely. Despite the role of genetics, CRC is also sensitive to macro-environmental factors. Few studies have ever compared across different countries/regions to suggest possible macro-environmental risk factors of CRC. We estimated the effects of age, period and cohort on the changes of incidence of colorectal cancer across different countries/regions.MethodsPoisson regression age-period-cohort (APC) models were conducted to estimate the age, period and cohorts effects on CRC incidence across the West (i.e., the UK, the US and Australia) and Asia (i.e. Japan, Hong Kong, Shanghai, Singapore and India). We maximized the length of the study period according to each country’s data availability.ResultsWestern populations show upward inflections for their 1950s–1960s cohorts, while Asian populations (except India) show downward inflections for their 1950s cohorts. Japanese population also shows upward inflections for its 1960s cohorts, similar to the Western populations. There are apparent upward inflections towards the more recent cohorts for Hong Kong, Shanghai and Singapore; nevertheless, the confidence intervals are wider towards the more recent cohorts.ConclusionOur findings imply an increasing risk of CRC in both Western and Asian populations as their younger cohorts reach older ages. These findings are consistent with the life course argument that macro-environmental changes associated with socio-economic development have specific effects that extend over the life course. Actions that pertain to altering lifestyle-related exposures over the life course are of great importance in combating young CRC risks in the future.     

Geographic disparities of breast cancer incidence in Portugal at the district level: A spatial age-period-cohort analysis, 1998-2011

BackgroundBreast cancer is the most common malignancy in women world-wide and the most common cause of cancer deaths, which can often be managed with early diagnosis and subsequent treatment. Here, we focus on geographic disparities in incidence within Portugal for three age groups of women (30−49; 50−69; 70−84 years).MethodsAge-period-cohort (APC) models are widely used in cancer surveillance, and these models have recently been extended to allow spatially-varying effects. We apply novel spatial APC models to estimate relative risk and age-adjusted temporal trends at the district level for the 20 districts in Portugal. Our model allows us to report on country-wide trends, but also to investigate geographic disparities between districts and trends within districts.ResultsAge-adjusted breast cancer incidence was increasing over 1998–2011 for all three age groups and in every district in Portugal. However, we detect spatially-structured between-district heterogeneity in relative risk and age-adjusted trends (Net Drifts) for each of the three age groups, which is most pronounced in the highly-screened (50−69yo) and late-onset (70−84yo) groups of women.ConclusionsWe present evidence of disparities in breast cancer incidence at a more granular geographic level than previously reported. Some disparities may be due to latent risk factors, which cannot be accounted for by age, birth year, and geographic location alone.ImpactOur study motivates resuming data collection for breast cancer incidence at the district level in Portugal, as well as the study of exogenous risk factors.     

Modeling Exposure Intensity and Susceptibility-Latency Effect from Retrospective Cohort Data - Application to Lung Cancer Mortality in Blackfoot Disease Endemic Area in Taiwan

It is challenge in epidemiology to characterize the temperol aspect of exposure-disease association. The authors propose a stochastic model to deal with exposures that are time-dependent and exhibit susceptibility and latency effects. The model is applied to a retrospective cohort data on lung cancer mortality in the blackfoot disease endemic area in Taiwan. The authors compare the proposed model with the multistage model, the back-calculation model, the catalytic model, and the age-period-cohort models.     

Trends in breast and cervical cancer in India under National Cancer Registry Programme: An Age-Period-Cohort analysis

BackgroundTrend analysis in cancer quantifies the incidence rate and explains the trend and pattern. Breast and cervical cancers are the two most common cancers among Indian women which contributed 39.4 % to the total cancer in India for the year 2020. This study aimed to report the time trends in cancer incidence of breast and cervical cancer using Age–Period–Cohort (APC) model from five Population Based Cancer Registries (PBCRs) in India for the period of 1985–2014.MethodAge-Period-Cohort model was fitted to five PBCRs of Bangalore, Chennai, Delhi, Bhopal and Barshi rural for breast and cervical cancer for 25−74 age-groups. The Estimated Annual Percent Change (EAPC) was calculated. Rate Ratio (RR) of cohort effects were estimated with a constraint of period slope to be zero (p = 0) since cohort has a stronger association with incidence than period.ResultA significant increase was noted in breast cancer in all PBCRs (EAPC, Range: Delhi, 1.2 % to Bangalore, 2.7 %) while significant decrease in cervical cancer (EAPC, Range: Bangalore -2.5 % to Chennai, -4.6 %) from all the PBCRs including Barshi rural during the period. RR estimates for breast cancer showed increasing trend whereas cervical cancer showed decreasing trend in successive birth cohorts across all five PBCRs.ConclusionIn both breast and cervical cancers, a significant age, cohort and period effect was noted in Bangalore, Chennai and Delhi. Despite period effect, the cohort effect was predominant and it may be attributed to the generational changes in risk factors among cancer breast and cervix.