title: A methodological issue in the analysis of second-primary cancer incidence in long-term survivors of childhood cancers.
abstract: Survival of childhood cancer patients has increased remarkably in the last several decades due to therapeutic improvements. Associated with this progress is the emerging need to accurately assess/minimize late effects of cancer therapy in long-term survivors. This paper considers a methodological issue in assessing the risk of second-primary malignant neoplasms, a major late effect of concern, using second-primary female breast cancer as an example. In the assessment of second-primary malignant neoplasm risk, attained age is a critical factor that must be taken into account. Even with follow-up of decades, childhood-cancer survivors are still at relatively young ages for developing adult-onset diseases. Attained ages at follow-up, however, modify cancer risk considerably; for example, in the general population, women aged 40 years have about fivefold increased breast cancer risk compared with women aged 30 years. A failure to account for the natural age-associated increase of risk could alter, or even reverse, analytical conclusions. This problem was studied empirically by both descriptive and regression analyses of two major studies of long-term childhood-cancer survivors, the Childhood Cancer Survivor Study (1975-1999) and the Late Effects Study Group (1955-1994). These showed appreciable differences in the analytical results by not accounting for the natural age-associated increase of risk, illustrating a significant impact of this methodological issue on study conclusions.
authors: Cancer Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. yyasui@fhcrc.org
authors: Yutaka
authors: Y
authors: Yasui
authors: Yan
authors: Y
authors: Liu
authors: Joseph P
authors: JP
authors: Neglia
authors: Debra L
authors: DL
authors: Friedman
authors: Smita
authors: S
authors: Bhatia
authors: Anna T
authors: AT
authors: Meadows
authors: Lisa R
authors: LR
authors: Diller
authors: Ann C
authors: AC
authors: Mertens
authors: John
authors: J
authors: Whitton
authors: Leslie L
authors: LL
authors: Robison
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D016016:Proportional Hazards Models; D018426:SEER Program; D014481:United States / Q000453:epidemiology