RT Journal Article
SR Electronic
T1 Impact of Misclassification in Genotype-Exposure Interaction Studies: Example of <em>N</em>-Acetyltransferase 2 (<em>NAT2</em>), Smoking, and Bladder Cancer
JF Cancer Epidemiology Biomarkers &amp; Prevention
JO Cancer Epidemiol Biomarkers Prev
FD American Association for Cancer Research
SP 1543
OP 1546
VO 13
IS 9
A1 Deitz, Anne C.
A1 Rothman, Nathanial
A1 Rebbeck, Timothy R.
A1 Hayes, Richard B.
A1 Chow, Wong-Ho
A1 Zheng, Wei
A1 Hein, David W.
A1 García-Closas, Montserrat
YR 2004
UL http://cebp.aacrjournals.org/content/13/9/1543.abstract
AB Errors in genotype determination can lead to bias in the estimation of genotype effects and gene-environment interactions and increases in the sample size required for molecular epidemiologic studies. We evaluated the effect of genotype misclassification on odds ratio estimates and sample size requirements for a study of NAT2 acetylation status, smoking, and bladder cancer risk. Errors in the assignment of NAT2 acetylation status by a commonly used 3-single nucleotide polymorphism (SNP) genotyping assay, compared with an 11-SNP assay, were relatively small (sensitivity of 94% and specificity of 100%) and resulted in only slight biases of the interaction parameters. However, use of the 11-SNP assay resulted in a substantial decrease in sample size needs to detect a previously reported NAT2-smoking interaction for bladder cancer: 1,121 cases instead of 1,444 cases, assuming a 1:1 case-control ratio. This example illustrates how reducing genotype misclassification can result in substantial decreases in sample size requirements and possibly substantial decreases in the cost of studies to evaluate interactions.