Capturing Complex Immune Genetics for Epidemiologic Research
AACR Education book
For the past five years our field has approached the study of genetic variation and its contribution to the development of cancer using Genome-Wide Association Study (GWAS) methodology. This has yielded a wealth of novel information and provided new directions for functional studies that will inform our understanding of both susceptibility and cancer development. However, one of the clear limitations of the GWAS platforms has been our inability to adequately capture and translate the genetic
... iation present for two drivers of immunity: the MHC (Major Histocompatibility Complex) which harbors the HLA genes critical for adaptive immunity, and the KIR (Killer Immunoglobulin Receptors), which are essential in innate immunity and determining the cytotoxic action of Natural Killer (NK) cells. Central to the prevention of cancer is the identification and removal of infected or abnormal cells (referred to as immune-editing, or immune surveillance, reviewed in (1) ). Both the innate and adaptive immune systems are involved in this process, and the complex traits that underlie this recognition of self vs non-self are encoded at the HLA and KIR regions. Given its role in delineating self from non-self, HLA has long been established as a key factor for successful organ transplant. In recent years, KIR genetic variation has emerged as a similarly important factor for successful bone marrow transplant (2). It follows that these same genetic traits should be important in the analogous (but reverse!) process of tumor immune surveillance. As we move into the post-GWAS era it is imperative that we devote our attention to these regions, which are likely to play a very prominent role in cancer susceptibility.