title: Germline polymorphisms as modulators of cancer phenotypes.
abstract: Identifying the complete repertoire of genes and genetic variants that regulate the pathogenesis and progression of human disease is a central goal of post-genomic biomedical research. In cancer, recent studies have shown that genome-wide association studies can be successfully used to identify germline polymorphisms associated with an individual's susceptibility to malignancy. In parallel to these reports, substantial work has also shown that patterns of somatic alterations in human tumors can be successfully employed to predict disease prognosis and treatment response. A paper by Van Ness et al. published this month in BMC Medicine reports the initial results of a multi-institutional consortium for multiple myeloma designed to evaluate the role of germline polymorphisms in influencing multiple myeloma clinical outcome. Applying a custom-designed single nucleotide polymorphism microarray to two separate patient cohorts, the investigators successfully identified specific combinations of germline polymorphisms significantly associated with early clinical relapse. These results raise the exciting possibility that besides somatically acquired alterations, germline genetic background may also exert an important influence on cancer patient prognosis and outcome. Future 'personalized medicine' strategies for cancer may thus require incorporating genomic information from both tumor cells and the non-malignant patient genome.
authors.affiliation: Duke-NUS Graduate Medical School, 2 Jalan Bukit Merah, Singapore. gmstanp@duke-nus.edu.sg
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D000818:Animals; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*
references.citation: Nat Genet. 2008 Jun;40(6):730-40
references.pmid: 18488030
references.citation: Br J Haematol. 2002 Jan;116(1):211-7
references.pmid: 11841419
references.citation: BMC Med. 2008 Sep 08;6:26
references.pmid: 18778477
references.citation: Nature. 2007 Jun 28;447(7148):1087-93
references.pmid: 17529967
references.citation: Nat Genet. 2003 May;34(1):23-4; author reply 25
references.pmid: 12721549
references.citation: Science. 2004 Jun 4;304(5676):1497-500
references.pmid: 15118125
references.citation: Cancer Cell. 2006 Apr;9(4):313-25
references.pmid: 16616336
references.citation: Clin Cancer Res. 2008 Jan 15;14(2):461-9
references.pmid: 18223220
references.citation: Nature. 2008 Apr 3;452(7187):633-7
references.pmid: 18385738
references.citation: Nature. 2005 Oct 27;437(7063):1299-320
references.pmid: 16255080
references.citation: Blood. 2006 Sep 15;108(6):2020-8
references.pmid: 16728703
references.citation: J Clin Oncol. 2006 Sep 20;24(27):4434-40
references.pmid: 16983111
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Nat Rev Genet. 2008 May;9(5):356-69
references.pmid: 18398418
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: N Engl J Med. 2002 Dec 19;347(25):1999-2009
references.pmid: 12490681
references.citation: J Clin Oncol. 2004 Apr 15;22(8):1382-8
references.pmid: 15007088