As was noted above, there are a number of inherited cancer susceptibility gene mutations,
such as xeroderma pigmentosum, Fanconi’s anemia, and ataxia telangiectasia. These types of
inherited defects that lead to cancer are generally caused by a deficiency in DNA repair pathways.
Almost certainly we have only scratched the surface of inherited cancer susceptibility
genes that make an individual more prone to developing cancer. Other susceptibility genes
may include alterations in the metabolic enzymes that metabolize drugs and environmental
toxins, polymorphisms in genes that regulate utilization of certain essential nutrients such as
folic acid, or inherited mutations in tumor suppressor genes.
The completion of the Human Genome Project allows a systematic approach to discovering
the genetic alterations thatmakeindividuals prone to developing various diseases. The Environmental
Genome Project is producing a catalogue of variation in genes involved in catabolizing toxins,
nutrient metabolism, and DNA repair.121 These data, which will be largely generated by detection
of single nucleotide polymorphisms (SNPs), will enable toxicologists and cancer biologists to predict
individual susceptibility to diseases triggered or promoted by environmental pollutants, diet,
and other lifestyle factors. Some examples of this SNP analysis approach are the increased susceptibility
of individuals with altered folate metabolism genes to develop leukemia after benzene
exposure and the ethnic variation in the BRCA1 gene SNPs that affect susceptibility to
breast cancer.
