The etiology and prediction of breast cancer. Fourier transform-infrared spectroscopy reveals progressive alterations in breast DNA leading to a cancer-like phenotype in a high proportion of normal women.
BACKGROUND
The authors previously have shown by gas chromatography-mass spectrometry that the hydroxyl radical (.OH) induces alterations in the DNA base structure of the female breast, which are premalignant markers of breast cancer. Fourier transform-infrared (FT-IR)-spectroscopy also has a high potential for revealing a broad array of structural changes in DNA that may provide important new insight into breast cancer etiology and prediction.


METHODS
DNA from normal reduction mammoplasty tissue, invasive ductal carcinoma, and nearby microscopically normal tissue was analyzed by FT-IR spectroscopy. Statistical models based on DNA spectral properties were developed and compared with a statistical model previously used with base modifications.


RESULTS
Substantial differences were found in the spectral properties of DNA from women with normal and cancerous breast tissue, indicating an ability to discriminate cancerous tissue from noncancerous tissue with a sensitivity and specificity of 83%. Most importantly, the normal population was divided into subgroups in which a nonrandom progression was identified and a cancer-like DNA phenotype that was highly correlated (r > or = 0.90) with that of the patients with cancer was exhibited in 59% of the women. The spectral data, which also were highly correlated with the base-model data, were used to establish a model for predicting the probability of breast cancer. Consistent with the high cancer reoccurrence rate in the ipsilateral breast, 8 of 10 of the microscopically normal tissue specimens remaining after tumor excision were classified as cancerous using this model.


CONCLUSIONS
Progressive structural changes in the DNA of the normal female breast, leading to a premalignant cancer-like phenotype in a high proportion of women, are the basis for a new paradigm for understanding the etiology of breast cancer and predicting its occurrence at early stages of oncogenesis. The results also suggest therapeutic strategies for potentially reversing the extent of DNA damage, which may be useful in disease prevention and treatment.
Malins
D C
DC
Molecular Epidemiology Program, Pacific Northwest Research Foundation, Seattle, Washington 98122.
Polissar
N L
NL
Nishikida
K
K
Holmes
E H
EH
Gardner
H S
HS
Gunselman
S J
SJ
D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000209:etiology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000737:chemistry*; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008954:Models, Biological; D011230:Precancerous Conditions; D017550:Spectroscopy, Fourier Transform Infrared
D004273:DNA, Neoplasm