Journal of the National Cancer Institute Advance Access originally published online on September 9, 2008
JNCI Journal of the National Cancer Institute 2008 100(18):1318-1325; doi:10.1093/jnci/djn290
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© The Author 2008. Published by Oxford University Press.
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Evaluation of Bias in Familial Risk Estimates: A Study of Common Cancers Using Swedish Population-based Registers
Affiliation of authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Correspondence to: Kamila Czene, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77, Stockholm, Sweden (e-mail: kamila.czene{at}ki.se).
Background: Bias in estimates of familial cancer may result if population-based registers fail to identify relatives as affected when disease occurs before the start-up of registration (ie, "left-truncation" of family history).
Methods: Apparent familial relative risks (among offspring of parents with cancer) of colorectal, lung, breast, and prostate cancers and melanoma in a Swedish cohort were compared with relative risks in a simulated population. The study cohort (approximately 7 million individuals) was based on the Swedish MultiGenerational Register linked to the Swedish Cancer Register for the period 1961–2002. A similar population of related individuals (approximately 7 million) with complete family information was simulated by using the R-package PopLab and used to estimate the sensitivity of the observed family history. This sensitivity was then used to calculate corrected age group–specific and overall risks, which were compared with the apparent familial risks of cancer in the cohort.
Result: The apparent familial risks for colorectal, lung, breast, and prostate cancers and melanoma were 1.99 (95% confidence interval [CI] = 1.85 to 2.14), 2.05 (95% CI = 1.86 to 2.26), 1.84 (95% CI = 1.76 to 1.92), 2.33 (95% CI = 2.19 to 2.48), and 2.68 (95% CI = 2.35 to 3.07), with corresponding absolute rates of 3.69, 2.59, 16.05, 10.38, and 2.96 per 10 000 person-years, among offspring of parents diagnosed with the same cancer. Corrected age group–specific and overall estimates of the familial risks were close to these apparent risks for all studied cancers (all approximately 2.0), except for melanoma. For melanoma, the corrected estimate of 3.18 (95% CI = 2.73 to 3.64) was somewhat larger than the apparent estimate and was not included in the confidence interval for the apparent estimate. When the exposure of interest was a parent affected at a younger age, this bias was more pronounced; the apparent estimate for melanoma changed from 4.07 (95% CI = 3.21 to 5.16) to 5.67 (95% CI = 4.51 to 6.83) after correction.
Conclusions: For common cancers, risk estimates from the Swedish MultiGenerational cohort do not generally appear to be biased by left-truncation.
| CONTEXT AND CAVEATS Prior knowledge Bias in estimates of familial cancer risks may occur in population-based studies when family history is incomplete if relatives of study subjects are diagnosed with cancer before the beginning of cancer registration. Study design Corrected familial risks (due to a parent having cancer) of colorectal, lung, female breast, and prostate cancers and melanoma were calculated for 1961–2002 after comparing apparent risks among a Swedish cohort from the Swedish MultiGeneration Register linked to the national Cancer Register and risks from a simulated population, with complete family history, for this period. Study contribution Corrected familial risks were similar to the apparent risks for all cancers and were close to 2.0, except melanoma, for which the corrected value was approximately 3.2. Implications For most of the common cancers studied, the Swedish MultiGeneration Register provided unbiased familial risks. Study limitations The bias in familial risks of other types of cancer should be evaluated in this population and in other populations with national cancer registries before these results can be generalized to other types of cancer and to other populations. From the Editors
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Manuscript received February 11, 2008; revised June 23, 2008; accepted July 17, 2008.
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J Natl Cancer Inst 2008 100: 1269.
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