Pooling prospective studies to investigate the etiology of second cancers.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
Increased understanding of nontreatment risk factors for second cancers will provide valuable prevention and surveillance information.
Division of Cancer Epidemiology and Genetics;
Amanda
A
Black
Division of Cancer Epidemiology and Genetics;
Todd M
TM
Gibson
Division of Cancer Epidemiology and Genetics;
Meredith S
MS
Shiels
Division of Cancer Epidemiology and Genetics;
Yikyung
Y
Park
Department of Epidemiology and Biostatistics, George Washington University School of Public Health and Health Services, Washington, D.C.;
Kim
K
Robien
Division of Cancer Epidemiology and Genetics;
Demetrius
D
Albanes
Division of Cancer Epidemiology and Genetics;
Stephanie J
SJ
Weinstein
Division of Cancer Epidemiology and Genetics;
Laura E Beane
LE
Freeman
Division of Cancer Epidemiology and Genetics;
Gabriella
G
Andreotti
Division of Cancer Epidemiology and Genetics;
Mark P
MP
Purdue
Division of Cancer Epidemiology and Genetics;
Joseph F
JF
Fraumeni
Division of Cancer Epidemiology and Genetics;
Patricia
P
Hartge
Division of Cancer Epidemiology and Genetics;
Margaret A
MA
Tucker
Division of Cancer Epidemiology and Genetics;
Robert N
RN
Hoover
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; and.
James R
JR
Cerhan
Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York.
Anne
A
Zeleniuch-Jacquotte
Division of Cancer Epidemiology and Genetics;
Rochelle E
RE
Curtis
Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, DHHS, Rockville, Maryland;
Joanne
J
Elena
Division of Cancer Epidemiology and Genetics;
Joshua N
JN
Sampson
Division of Cancer Epidemiology and Genetics;
Amy
A
Berrington de Gonzalez
Division of Cancer Epidemiology and Genetics; mortonli@mail.nih.gov.
Lindsay M
LM
Morton
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015340:Epidemiologic Research Design; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology*; D011446:Prospective Studies