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Carcinogenesis Advance Access published online on August 19, 2005
Carcinogenesis, doi:10.1093/carcin/bgi215
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received July 2, 2005
Revised August 7, 2005
Accepted August 12, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Accurate genotyping from paraffin embedded normal adjacent tissue of breast cancer

Bin Xie 1, Simone S. Cummings 1, Baljit Singh 2, Hong He 1, Susan McCann 3, Kirsten Moysich 3, Jo L. Freudenheim 3, and Peter G. Shields 1*

1 Cancer Genetics and Epidemiology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC
2 Cancer Genetics and Epidemiology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC; Present address: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
3 Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, NY

* To whom correspondence should be addressed.
Peter G. Shields, E-mail: pgs2{at}georgetown.edu


  Abstract

Genetic polymorphism analysis for disease risk is widely used in epidemiology studies; blood or oral cavity cells are the most widely used source of DNA. However, these types of samples are not always available, particularly for studies conducted years ago. An alternative potential source of patient DNA exists in the form of paraffin-embedded normal adjacent tissue of tumor samples, which are collected and stored routinely for clinical use. The use of such can be conceptually problematic, however due to the presence of field cancerization in surrounding normal tissue, with the possible presence of chromosomal loss. Specifically, loss of heterozygosity (LOH) might bias the genotyping results and cause genotype misclassification. However, field cancerization and LOH might not be an issue because LOH is not easily found unless there is careful microdissection of only tumor cells (leaving stromal, inflammatory and fat cells), for example, by laser-capture microdissection. In this study, we set out to determine the degree of genotype misclassification from normal adjacent tissues of tumors, if any, by comparing these results with blood genotyping. We examined samples from 106 subjects with breast cancer, analyzing 5 different genotypes selected from regions commonly know to have LOH in breast cancer. These genotypes were methylenetetrahydrofolate reductase (MTHFR), oxoguanosine glycosylase 1 (hOGG1), dopamine {beta}-hydroxylase (DBH), dopamine receptor D2 (DRD2), and NAD(P)H dehydrogenase quinone 1 (NQO1), conducted by real time PCR and TaqMan genotyping analyses. We found that among these 5 genotypes and 106 comparisons, there was a 100% concordance for genotyping from normal tissue adjacent to tumor and blood. Our findings indicate that the use of adjacent normal tissues provides accurate genotyping results with high specificity. Although this study only used breast tumor samples, and may be applicable only to breast cancer studies, we expect the results to be applicable to other types of cancer.

Keywords: genotyping; method.
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