ABSTRACT
Human genetic polymorphisms in metabolic activation and detoxification pathways appear to be important sources of inter-individual variation in susceptibility to cancer. This chapter briefly describes methods for detecting DNA sequence polymorphisms, which are inherited variations in a DNA sequence at a specific location in the genome. The analysis of polymorphisms and mutations has classically been an area in which polymerase chain reaction has flourished. Polymorphisms often occur at restriction enzyme recognition sites and alter restriction enzyme digestion patterns, allowing detection by restriction fragment length polymorphism analysis. The chapter discusses basic approaches that may be used to examine base-pair changes in the DNA sequence. For each DNA sample tested, one first determines the genotype for each restriction digest. By comparing results for all digests, one can determine the composite genotype and phenotype. Population-based studies are moving rapidly toward high-throughput genotyping methods, which potentially allow the processing of thousands of samples per day.
