%0 Journal Article
%T Germline polymorphisms as modulators of cancer phenotypes
%A Patrick Tan
%J BMC Medicine
%D 2008
%I BioMed Central
%R 10.1186/1741-7015-6-27
%X A major advancement of genetic research in recent years has been the explosion of genome-wide association studies (GWAS) in the literature from different investigators and laboratories [1]. The completion of the reference human genome sequence, and its subsequent comparison across different human sub-populations, has identified millions of genetic polymorphisms that differ between different individuals, families, and ethnic groups [2]. With the availability of increasingly affordable chip technologies for interrogating these polymorphisms en masse in individual genomes, it is now possible to consider identifying, on a comprehensive genome-wide scale, all genes and genetic variants associated with human disease. In the area of cancer, GWAS studies have been performed for multiple different tumor types including breast, lung, and stomach cancers [3-5]. These studies have both reconfirmed previously known disease genes (eg FGFR2 in breast cancer) [3], and also identified novel genetic loci, such as TNRC9, MAP3K1, and LSP1 for breast cancer [3] and the nicotinic acetylcholine receptor subunits in lung cancer [4]. To date, the majority of reported GWAS studies have employed a case-control design, where affected individuals with a disease are compared against a matched population of non-affected normal controls. The genetic variants identified using such case-control designs thus represent 'disease susceptibility' loci that can either increase or decrease an individual's risk to developing disease. A report published this month in BMC Medicine by Van Ness et al. [6] seeks to extend this theme, by asking whether germline polymorphisms can influence not simply the onset of disease, but the actual course of disease prognosis in cancer.The focus of Van Ness et al. on the cancer patient germline is particularly notable when one considers how the concept of cancer as an acquired somatic disease has dominated the field. In this model, tumor cells are believed to arise as a conse
%U http://www.biomedcentral.com/1741-7015/6/27