SNPs in cancer research and treatment

Abstract

Genetic variation in the human genome is an emerging resource for studying cancer, a complex set of diseases characterised by both environmental and genetic contributions. The number of common germ-line variants is great, on the order of 10-15 million per person, and represents a remarkable opportunity to investigate the aetiology, interindividual differences in treatment response and outcomes of specific cancers. The study of genetic variation can elucidate critical determinants in environmental exposure and cancer, which could have future implications for preventive and early intervention strategies. However, we are in the initial stages of characterising the tools (i.e., the single-nucleotide polymorphism, SNP) to rigorously analyse the genetic contributions to complex diseases, such as cancer. If the promise of the genomic era is to be realised, we must integrate this information into new strategies for implementation in both public health measures and, most importantly, provision of individual cancer-related care.

Figure 1

Determination of haplotypes in unrelated and related subjects. Haplotype structure is determined in pedigrees on the basis of genotype analysis at three different sites of a chromosomal region. The major and minor alleles are represented by A/a, B/b and C/c, respectively. The haplotypes can be deduced from the data in the table, and follow classical Mendelian inheritance. Haplotypes can be inferred in unrelated subjects by applying statistical algorithms to estimate haplotypes, based on genotype data. However, this will not determine a haplotype unequivocally, rather giving a haplotype with a statistical probability of being correct. Although this approach is most widely used because of its cost effectiveness, other methods exist that will determine haplotypes conclusively. On occasion, one can isolate DNA clones from a single chromosome for direct sequence analysis or selectively amplify using allele-specific oligonucleotide primers.