This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rundle, A. G. Articles by Ahsan, H. Search for Related Content PubMed PubMed Citation Articles by Rundle, A. G. Articles by Ahsan, H. Related Collections Epidemiology and Prevention Epidemiology and Prevention: Genetics and Biomarkers

Design Options for Molecular Epidemiology Research within Cohort Studies

¹ Department of Epidemiology, Mailman School of Public Health and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York; ² Imperial College London, London, United Kingdom; and ³ University of Torino, Turin, Italy

Requests for reprints: Andrew Rundle, Department of Epidemiology, Mailman School of Public Health and Herbert Irving Comprehensive Cancer Center, Columbia University, 722 West 168th, Room 730, New York, NY 10032. Phone: 212-305-7619; Fax: 212-305-9413. E-mail: agr3{at}columbia.edu

Past discussions of the relative strengths of nested case-control and case-cohort designs have not fully considered cohorts with stored biological samples in which biomarker analyses are planned. Issues related to biomarker analyses can affect an investigator's choice of design and the conduct of these two designs. The key issues identified are effects of analytic batch, long-term storage, and freeze-thaw cycles on biomarkers. In comparison with the nested case-control design, the case-cohort design is less able to handle these challenges. Problems arise because most implementations of the case-cohort design do not allow for simultaneous evaluation of biomarkers in cases and reference group members, and there is no matching. By design, the nested case-control study controls for storage duration and the batching of biological samples from cases and controls is logistically simple. The allowance for matching also means that subjects can be matched on the number of freeze-thaw cycles experienced by the biological sample. However, the matching generates complex data sets that can be more difficult to analyze, and the costly biomarker data generated from the controls has few uses outside of testing the specific hypotheses of the study. In addition, because the same subject can serve as a control and a case, or multiple times as a control, biomarker analyses and sample batching can be more complex than initially anticipated. However, in total, of the two designs, the nested case-control study is better suited for studying biomarkers that can be influenced by analytic batch, long-term storage, and freeze-thaw cycles.

This article has been cited by other articles:

				X.-J. Ma, R. Salunga, S. Dahiya, W. Wang, E. Carney, V. Durbecq, A. Harris, P. Goss, C. Sotiriou, M. Erlander, et al. A Five-Gene Molecular Grade Index and HOXB13:IL17BR Are Complementary Prognostic Factors in Early Stage Breast Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2601 - 2608. [Abstract] [Full Text] [PDF]

				P. Vineis and F. Perera Molecular Epidemiology and Biomarkers in Etiologic Cancer Research: The New in Light of the Old Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 1954 - 1965. [Abstract] [Full Text] [PDF]

				R. C Brown, T. Dwyer, C. Kasten, D. Krotoski, Z. Li, M. S Linet, J. Olsen, P. Scheidt, D. M Winn, and for the International Childhood Cancer Cohort Cons Cohort Profile: The International Childhood Cancer Cohort Consortium (I4C) Int. J. Epidemiol., August 1, 2007; 36(4): 724 - 730. [Full Text] [PDF]

				A. D. Heymann, G. Chodick, E. Kramer, M. Green, and V. Shalev Pemphigus Variant Associated With Penicillin Use: A Case-Cohort Study of 363 Patients From Israel Arch Dermatol, June 1, 2007; 143(6): 704 - 707. [Abstract] [Full Text] [PDF]

				A. Besaratinia and G. P. Pfeifer Investigating human cancer etiology by DNA lesion footprinting and mutagenicity analysis Carcinogenesis, August 1, 2006; 27(8): 1526 - 1537. [Abstract] [Full Text] [PDF]