Gene polymorphisms and susceptibility to coronary artery disease

As pediatric cancer survivors age, long-term cardiovascular complications related to chemotherapeutic toxicities, as well as development of premature coronary artery disease (CAD) from radiation and increased prevalence of CAD risk factors such as obesity, are likely to become more prevalent. Despite advances in our understanding of CAD in the general population, a large amount of the variance in development of disease is unexplained. Given the strong heritability of CAD, some of this may be attributable to genetics. Premature CAD in particular segregates in families, and twin studies have shown that the genetic contribution is greater in premature CAD. In this article, we present a brief review of the literature on the genetics of CAD. Over 30 monogenic disorders feature CAD phenotypes. Recently, however, interest has shifted to understanding the genetic variation contributing to common, complex disease, where disease risk is polygenic and characterized by environmental factors, and gene-environment interactions. CAD epitomizes such a disease, and highlights the inherent difficulties in understanding the underlying genetic architecture of such diseases. Long-term cardiovascular complications in patients who survive pediatric cancers result in significant morbidity and mortality in this population. Clinicians need to be aware of screening and treatment strategies for primary and secondary prevention of cardiovascular complications in this group. Further research is necessary to define the epidemiology and risk factors of premature CAD in survivors of pediatric cancers, and to determine whether candidate genes for cardiovascular disease in the general population are also susceptibility genes in this vulnerable population.