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Int J Mol Epidemiol Genet 2011;2(2):95-113

Original Article
Design and validity of a clinic-based case-control study on the molecular
epidemiology of lymphoma

James R Cerhan, Zachary S. Fredericksen, Alice H. Wang, Thomas M. Habermann, Neil E. Kay, William R. Macon, Julie M.
Cunningham, Tait D. Shanafelt, Stephen M. Ansell, Timothy G. Call, Thomas E. Witzig, Susan L. Slager, Mark Liebow

Division of Epidemiology and Division of Biostatistics, Department of Health Sciences Research; Division of Hematology and
Division of General Internal Medicine, Department of Medicine; Division of Hematopathology and Division of Experimental
Pathology, Department of Laboratory Medicine and Pathology; College of Medicine, Mayo Clinic, Rochester, Minnesota.

Received February 17, 2011; accepted April 3, 2011; Epub April 5, 2011; published May 15, 2011

Abstract: We present the design features and implementation of a clinic-based case-control study on the molecular
epidemiology of lymphoma conducted at the Mayo Clinic (Rochester, Minnesota, USA), and then assess the internal and
external validity of the study.  Cases were newly diagnosed lymphoma patients from Minnesota, Iowa and Wisconsin seen at
Mayo and controls were patients from the same region without lymphoma who had a pre-scheduled general medical
examination, frequency matched on age, sex and residence.  Response rates were similar for cases (67%) and controls
(70%).  Response rates were lower for cases and controls over age 70 years, cases with more aggressive disease, and
controls from the local area, although absolute differences were modest.  Cases and controls were well-balanced on age, sex,
and residence characteristics.  Demographic and disease characteristics of NHL cases were similar to population-based
cancer registry data.  Control distributions were similar to population-based data on lifestyle factors and minor allele
frequencies of over 500 SNPs, although smoking rates were slightly lower.  Associations with NHL in the Mayo study for
smoking, alcohol use, family history of lymphoma, autoimmune disease, asthma, eczema, body mass index, and single
nucleotide polymorphisms in TNF (rs1800629), LTA (rs909253), and IL10 (rs1800896) were at a magnitude consistent with
estimates from pooled studies in InterLymph, with history of any allergy the only directly discordant result in the Mayo study.  
These data suggest that this study has high internal and external validity.  This framework may be useful to others who are
designing a similar study. (IJMEG1102002).

Keywords: Case-control study, etiology, lymphoma, molecular epidemiology, validity

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Address all correspondence to:
Dr. James R. Cerhan
Department of Health Sciences Research
Mayo Clinic College of Medicine
200 1st Street SW
Rochester, MN  55905, USA