Seregard S, Lundell G, Svedberg H, Kivelה T: Incidence of retinoblastoma from 1958 to 1998 in Northern Europe. Advantages of birth cohort analysis

Ophthalmology 2004;111:1228-1232.

1 Ophthalmic Pathology and Oncology Service, St. Erik’s Eye Hospital, Stockholm, Sweden

2 Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden

3 Oncology and Pediatric Ophthalmology Services, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland Received 26 February 2003; accepted 11 October 2003.

Available online 31 May 2004.

Abstract

Purpose

To assess change in incidence of retinoblastoma in Northern Europe and to compare commonly used methods for calculating its incidence against birth cohort analysis.

Design

Retrospective cohort study.

Participants

Individual and pooled data of 291 Swedish and 174 Finnish children diagnosed with retinoblastoma between 1958 and 1998.

Main outcome measures

Incidence per 1 million children younger than 5 years of age (37 812 035 person- years at risk) and per 100 000 live births (7 152 265 live-born children at risk).

Methods

Data were from Swedish and Finnish Cancer Registries and corresponding national referral centers for retinoblastoma. Incidence was calculated both by standard analysis per children younger than 5 years of age and per live births, and by birth cohort analysis. Curves were smoothed with robust, locally weighted regression. Linear regression was used to fit pooled data.

Results

The number of new retinoblastoma cases per year ranged from 0 to 13 (113 per birth cohort) in Sweden and from 0 to 10 in Finland (19 per birth cohort). The mean incidence was 11.8 (95% confidence interval [CI], 10.513.1) and 11.2 (95% CI, 9.413.0) per 1 million children younger than 5 years of age in Sweden and Finland, respectively, and 6.7 (95% CI, 5.97.5) and 6.2 (95% CI, 5.37.2) per 100 000 live births, respectively. Analysis based on year of diagnosis suggested moderate increase in incidence since 1990, but by birth cohort analysis, incidence rates were stable for both countries. The pooled incidence by birth cohort was 6.0 (95% CI, 5.46.6) per 100 000 live births, corresponding to 1 in 16 642 (95% CI, 15 10518 528) live births. Conclusions

The data suggest that the incidence of retinoblastoma is stable in Northern Europe. Analysis based on birth cohort is recommended for future epidemiologic studies, because it minimizes the effect of variable age at diagnosis of this developmental cancer and results in less variable incidence rates than standard analysis based on year of diagnosis.

Retinoblastoma is caused by inactivation of a dominant tumor suppressor gene, which controls cell cycling.[1] All bilateral and up to 15% of unilateral retinoblastomas result from germline mutations of this gene and are inherited as an autosomal dominant trait. [2 and 3] Half of the offspring to patients with hereditary retinoblastoma carry the mutant gene, and retinoblastoma develops in 90% of them. In medically advanced regions such as North America and Europe, retinoblastoma is diagnosed early, the chances of salvaging the eye and remaining vision are good, and the risk of dying of retinoblastoma is small. In fact, trilateral retinoblastoma [4] and second cancers [5] in these areas are now the most frequent causes of death among patients with hereditary tumors. [6 and 7]

Given these favorable prospects, patients with hereditary retinoblastoma are increasingly likely to produce offspring. Assuming that the mutation rate is stable, this would generate an increase in the incidence of retinoblastoma. To test for this hypothesis and to compare various methods of calculating the incidence of retinoblastoma, we analyzed the incidence rate during 4 decades, from 1958 to 1998, in 2 neighboring North European countries, Sweden and Finland.