Single nucleotide polymorphisms and cancer susceptibility

Abstract

Cancer susceptibility is determined by exposure to environmental factors and inheritance of genetic factors, which act either alone or in combination to influence likelihood of disease. Twin studies have provided evidence that the familial aggregation of cancer results from inherited factors. Known highly penetrant rare mutations account for some but not all of this familial risk. The nature of the remaining familial risk is unknown, but multiple-case families have failed to provide evidence of linkage to novel loci in recent studies, and it is more plausible that a substantial proportion will be conferred by a number of low-penetrance genetic variants with relatively high population frequency. Individually these polymorphisms will confer only modest increases in risk, but when considered collectively, and in combination with relevant environmental factors, they may confer substantial susceptibility. This concept has been termed the common disease-common variant hypothesis, and single nucleotide polymorphisms (SNPs), which are the most abundant sequence variation in the human genome, are thought to account for the majority of such common low-penetrance cancer susceptibility variants.