ABSTRACT

Biomarker(s) Reference

Intermediate biomarkers for colorectal cancer includes expression of mucins, intermediate €laments and cytoskeletal proteins, and the structure and expression of a variety of genes associated with normal and abnormal cell development

Rectal cell proliferation as an intermediate biomarker in colorectal cancer (altered distribution of proliferating cells in colorectal crypts)

p53 as an intermediate biomarker in Barrett’s esophagus 45

De€nition of biomarkers of exposure, biomarkers of susceptibility, and biomarkers of effect. The use of intermediate biomarkers to determine cancer risk at very early stages

Hypomethylation of DNA as an intermediate biomarker in colorectal carcinogenesis 47

Nuclear matrix composition as an intermediate biomarker in squamous cell carcinoma 48

Use of quantitative reverse transcription-polymerase chain reaction (quantitative RT-PCR) to measure intermediate biomarkers in tissue biopsies from oral cancer patients

Biomarker(s) References

Cellular proliferation (labeling index), apoptosis, polyamine metabolism, arachidonic acid metabolism, genetic alterations

NAD(P)H and collagen as biomarkers for epithelial precancerous lesions 51

Cytogenetic changes (aneusomy demonstrated by †uorescence in situ hybridization [FISH] analysis) as biomarker for preinvasive changes in the development of lung cancer

52-54

Proliferating cell nuclear antigen (PCNA), p53, and polyamines as biomarker for early skin tumorogenesis

Discussion of precancerous biomarkers for cervical cancer including human papillovirus DNA, E6/E7 mRNA, minichromosome maintenance protein, PCNA, MIB-1, cyclin E and p161NK4A

Use of FISH to detect chromosomal abnormalities in preinvasive ulcerative colitis neoplasia

NH

NN

N

O

NH2

H2C

Cl

Vinyl chloride

CYP2E1

H2C

O

H C Cl

Chloroethylene oxide

NH

N H

N

N+

O

+

Guanine

NH2

O

7-(2-Oxoethyl)guanine

N

NN

N

O

NH

NN

N

O

NH2 Guanine

N H

O

CH2

H2C

CH2

H2C

CH3

+4-Oxo-2-nonenal

Hepatanone-ethenoguanine

FIGURE 3.1 The formation of adducts of nucleic acids. The term adduct refers to the combination of two different materials to form a compound. While this could refer to the chemical interaction of any two chemicals to form a derivative compound, the term adduct appears to have a unique application within nucleic acid chemistry. Shown here are adducts of vinyl chloride with guanosine (Weyandt, J., Ellsworth, R.E., Hooke, J.A. et al., Environmental chemicals and breast cancer risk-A structural chemistry perspective, Curr. Med. Chem. 15, 2680-2701, 2008) and the reaction of 2-hydroxy-4-nonenal with guanosine (Blair, I.A., DNA adducts with lipid peroxidation products, J. Biol. Chem. 283, 15545-15549, 2008). See also Broyde, S., Wang, L., Zhang, L. et al., DNA adduct structure-function relationships: Comparing solution with polymerase structures, Chem. Res. Toxicol. 21, 45-52, 2008; Gallo, V., Khan, A., Gonzales, C. et al., Validation of biomarkers for the study of environmental carcinogens: A review, Biomarkers 13, 505-534, 2008.