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Age at Immigration and Duration of Stay in Relation to Risk for Testicular Cancer Among Finnish Immigrants in Sweden

Anders Ekbom, Lorenzo Richiardi, Olof Akre, Scott M. Montgomery, Pär Sparén

Affiliations of authors: A. Ekbom, Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden, and Department of Epidemiology, Harvard School of Public Health, Boston, MA; L. Richiardi, O. Akre, P. Sparén, Department of Medical Epidemiology, Karolinska Institutet, Stockholm; S. M. Montgomery, Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital.

Correspondence to: Anders Ekbom, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, M9:01, SE-171 76 Stockholm, Sweden (e-mail: Anders.Ekbom{at}medks.ki.se).

ABSTRACT

Although the incidence of testicular cancer is increasing, substantial differences in incidence between countries and populations exist. These differences cannot be explained solely by genetic differences, but environmental exposures, particularly early exposures, have been implicated in the etiology of testicular cancer. To assess whether early exposures contribute to the incidence of testicular cancer, we identified 93 172 Finnish men who immigrated to Sweden between 1969 and 1996 and followed them for the occurrence of testicular cancer. The risk of testicular cancer was lower for Finnish immigrants to Sweden than for the Swedish general population (standardized incidence ratio [SIR] = 0.34, 95% confidence interval [CI] = 0.21 to 0.53). The reduced risk was associated with both seminomas and non-seminomas. Neither age at immigration nor duration of stay in Sweden had any impact on the reduced risk. Although the type of environmental exposures remains unknown, the results strongly indicate that early exposures are major determinants for testicular cancer.


For at least 50 years, there has been an unexplained epidemic of testicular cancer in several populations (1,2), although there is a marked difference in incidence among countries. For example, the incidence of testicular cancer is more than twice as high in Sweden as it is in Finland and twice as high in Denmark as it is in Sweden (3).

The increasing trend in incidence is almost entirely the result of a birth cohort phenomenon and not a period effect, implying that lifetime risk of testicular cancer is highly dependent on year of birth (4,5). The birth cohort pattern, together with findings of carcinoma in situ at young ages (6), has led to the conclusion that the exposures contributing to the rising incidence occur early in life, possibly in utero.

Assessing how environmental exposures can affect cancer risk is problematic because of the time lag between exposure and the appearance of cancer. However, evaluating risks among immigrant populations provides the means to assess the effect of the environmental risk of disease. Results from migrant studies conducted in Israel (7), Australia (811), and New Zealand (12) indicated that those who emigrate from low-incidence areas to high-incidence areas retain a low risk for testicular cancer. However, those studies (712) lacked statistical power and an estimate of testicular cancer incidence in the immigrant’s country of origin, which hindered any definitive conclusions.

Finns who have immigrated to Sweden constitute an ideal population for studying the risk of testicular cancer among immigrants for several reasons. First, a large number of people have emigrated from Finland to Sweden during the last 40 years. Second, both countries have detailed nationwide cancer registries. Third, there is a pronounced difference in the incidence of testicular cancer between Sweden and Finland (1). The results of a recent study (13) of Finnish immigrants in Sweden indicate that their incidence of testicular cancer is low and comparable to that of men from Finland (standardized incidence ratio [SIR] = 0.44, 95% confidence interval [CI] = 0.31 to 0.60). However, the study was confined to those who emigrated as adults and was not stratified by duration of stay. We therefore conducted a registry-based cohort study to investigate whether age at immigration to Sweden and duration of stay modify the risk for testicular cancer among Finnish emigrants.

All Swedish residents can be identified by their national registration number (14). The 10-digit number contains information on date of birth and sex. By using that number, Statistics Sweden—a national database—can obtain information regarding year of immigration and country of origin from the Total Population Register, which contains data from 1969 to the present. The study cohort consisted of 93 172 men born in Finland who immigrated to Sweden between 1969 and 1994. The age distribution of these immigrants is given in Table 1Go.


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Table 1. Number of Finnish immigrants by age at immigration from 1969 through 1994
 
The cohort members were followed from the date of immigration until the date of diagnosis of testicular cancer, death, emigration, or end of follow-up (December 31, 1996), whichever occurred first. Follow-up was done through linkage to three different Swedish registries: 1) the Swedish Emigration Registry (15), maintained by Statistics Sweden since 1969, provided data on the date of emigration for any Swedish resident taking up permanent residence outside of Sweden; 2) the Swedish Cancer Registry (16), maintained by the National Board of Health and Welfare since 1958 to which all Swedish physicians and pathologists are required by law to report cancer diagnoses, provided data on all incident testicular cancer cases and the histopathologic subtype (seminomas or non-seminomas); and 3) the Swedish Causes of Death Register (15), maintained by the National Board of Health and Welfare since 1952, provided the date of death and underlying cause of death for all deceased Swedish residents. All registries use the national registration number as an identifier. The completeness of the reporting for testicular cancer is close to 100% (16).

We calculated SIRs to estimate the relative risk of testicular cancer, by histologic type, for Finnish immigrants (17). The time period of observation was from immigration to censoring. The numbers of observed testicular cancers, by histologic type, in the cohort were divided by the numbers of expected testicular cancers, which were derived from the age and period-specific rates in the general Swedish population. We calculated 95% CIs for SIRs, assuming a Poisson distribution for recorded numbers (17). We used the background incidence rate of testicular cancer for the Finnish population to calculate the SIR for testicular cancer for immigrants relative to general Finnish population.

From 1969 through 1996, there were 21 testicular cancers among Finnish immigrants in Sweden. The expected number of testicular cancers calculated from the Swedish population was 58.3 (SIR = 0.34, 95% CI = 0.21 to 0.53). There were 10 seminomas (SIR = 0.36, 95% CI = 0.17 to 0.65), nine non-seminomas (SIR = 0.31, 95% CI = 0.14 to 0.59), and two cancers that could not be classified because the histopathologic code was missing. SIRs for all individuals with testicular cancer are stratified by three age groups at immigration and by histopathologic group (Table 2Go). The SIRs were low, regardless of age at immigration and histopathologic group. Similarly, duration of stay did not seem to modify the risk for testicular cancer (Table 2Go).


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Table 2. Standardized incidence rate (SIR) and 95% confidence interval (CI) for Finnish immigrants to Sweden from 1969 through 1994 by age at immigration and histopathologic type and duration of stay
 
There was no trend across birth cohort or dates of immigration; the SIRs associated with seminomas and non-seminomas were all less than one (data not shown). There was no statistically significant difference in the incidence of testicular cancer between Finns who immigrated to Sweden and the general Finnish population (SIR = 0.85, 95% CI = 0.47 to 1.15); there were no statistically significant trends for duration of follow-up, histopathologic group, or birth cohort. However, those who immigrated to Sweden between 1969 and 1978 had an SIR of 0.65 (95% CI = 0.37 to 1.08) whereas those who immigrated between 1979 and 1994 had an SIR of 1.20 (95% CI = 0.44 to 2.62), suggesting a difference by calendar time of immigration.

In this study, we have confirmed that, after moving to Sweden, Finnish immigrants have a lower incidence of testicular cancer, regardless of the histopathologic form of the disease, than native Swedish men (13). Furthermore, neither age at immigration nor duration of stay modified the decrease in risk. The findings are compatible with the hypothesis that lifetime risk of testicular cancer is determined early in life, possibly before birth.

Our study has several strengths. First, we collected data regarding the immigration of approximately 100 000 males for whom age and date of immigration could be readily identified. Second, we conducted a non-differential follow-up by using data from the Swedish Cancer Registry. However, the power of the study is limited because of the small number of testicular cancers, which hinders a detailed assessment of the relationship between age at immigration and risk of testicular cancer. Although underreporting of cancer diagnoses could have occurred, it is highly unlikely because of the age groups. Death from cancer for those under age 50 is likely to be reported. It is difficult to identify any potential confounder that could have biased our results.

Our findings may be explained by a combination of genetic and environmental factors. Genetic susceptibility to testicular cancer may differ between Swedish and Finnish populations. Testicular cancer has a relatively strong heritability component, and the two populations are not closely related genetically (18). By contrast, genetic variation cannot explain other geographic variations in incidence, such as the strong gradients between Finnish and Estonian or between Swedish and Danish populations (1). Moreover, the increasing trend in incidence of testicular cancer cannot be explained in terms of genetics. Thus, it is likely that differences between the populations with respect to exposure of environmental factors early in life explain the low incidence of testicular cancer among Finnish immigrants. It is highly plausible that susceptibility to these exposures occurs in utero when the testicles are developing and differentiating in the presence of numerous growth-regulating factors.

High socioeconomic status has been implicated as a risk factor for testicular cancer, although with decreasing strength over time (19). However, the uniformity in incidence of testicular cancer among the general Swedish population (20) argues against socioeconomic status as a confounder and thus against socioeconomic status as the underlying reason for the decreased risk among Finnish immigrants in Sweden. Socioeconomic status was a risk factor for testicular cancer in Finland during the 1970s, but it was no longer considered to have an impact during the 1990s (19). Because the majority of Finnish immigrants to Sweden were blue-collar workers, it is of interest that the SIRs were similar for Finnish immigrants and the general Finnish population during the later time period.

It is unclear exactly what exposures are implicated by our findings. Because of differences in the incidence of testicular cancer over time and among countries (20), government regulations and national habits should be considered in an attempt to identify the underlying etiologic agent(s) of testicular cancer. For example, differences among nations in dairy industry practices, in storage or preparation of food items (21), or in maternal smoking habits (22) may contribute to the development of testicular cancer but, so far, no specific agent has been identified. It should be noted that, given that testicular cancer risk is largely determined in utero, the differences in testicular cancer incidence between Sweden and Finland today would be attributable to environmental differences that were present approximately 30 years ago.

In conclusion, although we are still without a good hypothesis regarding what exposures are associated with an increased incidence of testicular cancer, our results strongly implicate early exposures as major determinants. If the types of exposures could be identified, then cancer prevention strategies could be designed to curb the testicular cancer epidemic.

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Manuscript received January 22, 2003; revised May 28, 2003; accepted June 4, 2003.


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