Factors critical to the design and execution of epidemiologic studies and description of an innovative technology to follow the progression from normal to cancer tissue.
The results obtained from experimental studies of estrogen carcinogenesis need validation in epidemiologic studies. Such studies present additional challenges, however, because variations in human populations are much greater than those in experimental systems and in animal models. Because epidemiologic studies are often used to evaluate modest differences in risk factors, it is essential to minimize sources of errors and to maximize sensitivity, reproducibility, and specificity. In the first part of this chapter, critical factors in designing and executing epidemiologic studies, as well as the influence of sample collection, processing, and storage on data reliability, are discussed. One of the most important requirements is attaining sufficient statistical power to assess small genetic effects and to evaluate interactions between genetic and environmental factors. The second part of this chapter describes innovative technology, namely, Fourier transform-infrared (FT-IR) spectra of DNA that reveal major structural differences at various stages of the progression from normal to cancer tissue. The structural differences become evident from wavenumber-by-wavenumber statistical comparisons of the mean FT-IR spectra of DNA from normal to cancer tissues. This analysis has allowed distinguishing benign tissues from cancer and metastatic tissues in human breast, prostate, and ovarian cancers. This analysis, which requires less than 1 microg of DNA, is predicted to be used for detecting early cancer-related changes at the level of DNA, rather than at the cellular level.
Garcia-Closas
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M
Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA.
Hankinson
S E
SE
Ho
S
S
Malins
D C
DC
Polissar
N L
NL
Schaefer
S N
SN
Su
Y
Y
Vinson
M A
MA
D004273:DNA, Neoplasm / Q000032:analysis; D015340:Epidemiologic Research Design; D005260:Female; D005583:Fourier Analysis; D012739:Gonadal Steroid Hormones / Q000032:analysis; D006801:Humans; D008297:Male; D015233:Models, Statistical; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors
D004273:DNA, Neoplasm; D012739:Gonadal Steroid Hormones