a Bureau of Reproductive and Child Health, Laboratory Centre for Disease Control, Canada.
b Cancer Bureau, Laboratory Centre for Disease Control, Canada.
Reprint requests to: Dr Yang Mao, Cancer Bureau, LCDC Building #6, Tunney's Pasture, AL 0601C1, Ottawa, Ontario, Canada K1A 0L2. E-mail: yang_mao{at}hc-sc.gc.ca
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Abstract |
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Methods From 1970 through 1995, 7296 cases of testicular cancer were registered in the Canadian provinces of Ontario, Saskatchewan and British Columbia. In addition to analyses of the secular trends by age group and birth cohort, an age-period-cohort (APC) model with standard Poisson assumptions was fitted to the data to assess the time effects.
Results The age-adjusted incidence rate for seminomas increased by 53%, from 1.5 per 100 000 males in 19701971 to 2.3 per 100 000 males in 19941995. Non-seminomas increased by 91%, from 1.1 to 2.1 per 100 000 males over the same period. Non-seminomas were more frequent at young ages whereas seminomas dominated in older ages. In contrast to seminomas, non-seminomas occurred predominantly among adolescent men (1519 years), with a fourfold increase between 19701971 and 19941995. Age-period-cohort modelling showed that the increase in the risk of both seminomas and non-seminomas followed a birth cohort pattern, but with differences in birth cohorts in addition to significantly distinct age patterns.
Conclusions Our findings support the hypothesis postulating aetiological heterogeneity in the development of seminomas and non-seminomas. We suggest that epidemiological studies of testicular cancer treat seminomas and non-seminomas separately.
Keywords Testicular cancer, cancer incidence, cohort effect, statistical models, Canada
Accepted 1 March 2000
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Introduction |
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Previous studies have suggested that the two main histological types of testicular cancer, namely seminomas and non-seminomas, may have distinctive aetiological profiles, even though they may share risk factors.7,8 Several epidemiological studies have examined time trends in the incidence of testicular cancer by histological type. Zheng et al. found that seminoma incidence peaks at about age 35 while non-seminomas peak about 10 years earlier among Connecticut (US) males.4 Wanderås et al. and Weir et al. also reported different age patterns in the incidence of the two histological subtypes of testicular cancer in Norway and Ontario, Canada.9,10 However, limited sample sizes in these studies prevented the investigators from extensively examining epidemiological difference between seminomas and non-seminomas. The paucity of clues to the aetiological heterogeneity of seminomas and non-seminomas suggests that further epidemiological studies are needed. This study examines the differences in the incidence patterns of testicular seminomas and non-seminomas using cancer registry data from the Canadian provinces of Ontario, Saskatchewan and British Columbia.
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Methods |
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The information regarding the CCR and the quality of Canadian cancer incidence data has been well documented.11,12 Generally, cancer data from these three provincial registries are comparable and reliable, and the completeness and the quality are rated highly.11,13 All three cancer registries used the Systematized Nomenclature of Pathology for histological classification before 1979, but those records were then converted to the International Classification of Disease for Oncology first edition (ICD-O-1) codes. By 19741978, 95% of testicular cancer cases had been confirmed by microscopy, and 1% by death certificates only.11,12 Testicular cancer was coded as 186 in the ICD-O-1. The cases were sub-divided into three broad histological groups: seminomas (ICD-O-1 morphology code 906), germ-cell non-seminomas or non-seminomas (ICD-O-1 morphology codes 907, 908, 910), and unspecified and other histological types of testicular cancer.
Secular trends in the incidence of seminomas and non-seminomas between 1970 and 1995 were estimated by linear regression models using the logarithms of the yearly rates for specific age groups of interest. The average annual per cent change (AAPC) was derived from the expression [exp(ß) 1] x 100, where ß is the regression coefficient of the model. All age-adjusted incidence rates were calculated using direct standardization with the World Standard Population serving as the standard.14
Analyses integrating age at diagnosis, time period of diagnosis and birth cohort were then performed. Age at diagnosis was grouped into 5-year intervals (1519 years to 7074 years). The period of diagnosis is reduced to cover from 1971 to 1995 in order to obtain five equal 5-year intervals. Corresponding to these age groups and time periods, a total of 16 overlapping 10-year birth cohorts (18961905 to 19711980, identified by the central year of birth from 1901 to 1976) were constructed.
Poisson regression modelling was used to estimate the age, period, and cohort effects with the assumptions that the number of cancer incident cases follows a Poisson distribution and the incidence rates are a multiplicative function of the included model parameters, making the logarithm of the rates an additive function of the parameters.1518 For example, the form of the age-period-cohort (APC) model was given by
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Results |
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The age-specific incidence rates for seminomas and non-seminomas by birth cohort were plotted in Figures 2 and 3, respectively. The incidence of seminomas showed a slight decline in men born between 1921 and 1941 and a dramatic increase in those born in later cohorts. The highest rates were observed among those aged 3039 years in all birth cohorts. Non-seminomas showed a plateau in early birth cohorts but a substantial increase in cohorts since 1941. The incidence rates were the highest among those aged 2529 years across the observed birth cohorts.
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Discussion |
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It is generally accepted that the frequent occurrence of testicular cancer in young men and the rarity of the disease in old men suggest that exposures to risk factors early in life, possibly in utero, are likely to be more important than exposures in adulthood.22,23 Also, the rapid increase in testicular cancer in young males is most likely the result of multiple risk factors acting in combination. However, the only well-established association is that between cryptorchism and testicular cancer.23,24 Many aetiological hypotheses have been proposed to explain the observed increase in testicular cancer. These include increases in exposure to oestrogen in utero, early life exposure to viruses, trauma to the testis, parental occupational exposures, effects from male sex hormones and genetic factors.2527
In most earlier analytical and descriptive epidemiological studies, testicular cancer has been treated as a single entity. Little attention was given to the differences in the epidemiological features of the two major histological types because of the unavailability of reliable histological data and the relatively small number of subjects with this disease. A few descriptive studies have examined the age-specific incidence patterns, although no distinct conclusive clues to aetiological differences were derived, in part because of the limited size of the population studied.4,28 On the other hand, analytical studies have suggested that aetiological heterogeneity between the two main histological types of testicular cancer may exist.8,29,30 One study further suggests that seminomas and non-seminomas may have different factors at the initiating or promoting stage of carcinogenesis.7 Another study has proposed that one causative factor might be responsible for the observed earlier increase in seminomas between 1935 and 1965 and another for the later increase in non-seminomas beginning in the 1970s.1
A study which focused on the analysis of testicular cancer in young boys and adolescent men using combined data from three European countries lends support to the hypothesis that testicular cancer in young boys is aetiologically distinct from testicular cancer in adults.31 This study also proposed that the particularly high increase (average annual increase of 6%) in the incidence rates of testicular cancer in adolescent men is likely the result of a secular trend towards earlier age at puberty. However, that study did not examine testicular cancer by histological type in either age group. Our study shows that non-seminomas predominated in both groups of males (boys and adolescents). This suggests that adolescent men, unlike older adults, are exposed to factors which predispose them to developing non-seminomas. This implies that non-seminomas which occurred mostly in children and younger men have one or more unique aetiological factors as opposed to seminomas. Nevertheless, some risk factors in perinatal and environmental exposures may be shared between the two types of testicular cancer.
Age-period-cohort modelling has considerable advantages over the simple analysis of temporal trends in cancer rates, though some limitations, such as the non-identifiability problem, are inherent.17,18 The coefficients obtained depend on the particular constraint imposed. In this analysis, however, the relative patterns for two histological types were based on constraints to obtain linear effects and departures from linearity as described by Holford.18 We observed substantial differences in the time trend effects in the incidence of testicular seminomas and non-seminomas. In most previous studies, in which testicular cancer was modelled as a single entity, birth cohort was identified as the determinant responsible for the observed increase.46 Testicular cancer is an anatomically and clinically distinct entity and diagnostic practice in this disease has not changed since at least the late 1970s.23 However, errors in cancer registration and coding may play a minor role in period effects over time. Therefore, we examined the time trends and compared the differences of incidence patterns between seminomas and non-seminomas in the presence of all the three time factors.
In summary, substantial epidemiological variations may provide clues for the development of specific testable aetiological hypotheses. It appears that no other cancer shows such distinctive incidence patterns between histological types as testicular cancer.4,23,28 Thus, in-depth analytical investigations are warranted to examine aetiological differences between the two main histological types of testicular cancer. We suggest that such studies treat testicular seminomas and non-seminomas separately.
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Acknowledgments |
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References |
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