Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers.
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.


RESULTS
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.
Leu
Monica
M
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Reilly
Marie
M
Czene
Kamila
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics; D015986:Confounding Factors, Epidemiologic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics; D013548:Sweden / Q000453:epidemiology