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Cancer Epidemiol Biomarkers Prev. 2014 Aug;23(8):1598-608. doi: 10.1158/1055-9965.EPI-14-0191. Epub 2014 May 15.

Pooling prospective studies to investigate the etiology of second cancers.

Author information

  • 1Division of Cancer Epidemiology and Genetics;
  • 2Department of Epidemiology and Biostatistics, George Washington University School of Public Health and Health Services, Washington, D.C.;
  • 3Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; and.
  • 4Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York.
  • 5Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, DHHS, Rockville, Maryland;
  • 6Division of Cancer Epidemiology and Genetics;



With over 13 million cancer survivors in the United States today, second cancers are of rapidly growing importance. However, data on nontreatment risk factors for second cancers are sparse. We explored the feasibility of pooling data from cohort studies of cancer incidence to investigate second cancer etiology.


We combined data from five prospective studies including more than 800,000 individuals. We compared study designs and populations; evaluated availability of and ability to harmonize risk factor data; compared incidence and survival for common first primary malignancies and incidence of second primary malignancies; and estimated sample size requirements.


Overall, 96,513 incident, first primary malignancies were diagnosed during 1985 to 2009. Incidence rates and survival following the first primary varied among the cohorts, but most of the heterogeneity could be explained by characteristics of the study populations (age, sex, smoking, and screening rates). A total of 7,890 second primary cancers (excluding original primary site) were identified, yielding sufficient statistical power (≥80%) for detecting modest associations with risk of all second cancers among survivors of common first primary malignancies (e.g., colorectal cancer); however, there were insufficient events for studying survivors of rarer cancers or identifying risk factors for specific second cancers.


Pooling data from cohort studies to investigate nontreatment risk factors for second primary cancers seems feasible but there are important methodologic issues-some of which are barriers to specific research questions-that require special attention.


Increased understanding of nontreatment risk factors for second cancers will provide valuable prevention and surveillance information.

©2014 American Association for Cancer Research.

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