Germline polymorphisms as modulators of cancer phenotypes.
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.
Tan
Patrick
P
Duke-NUS Graduate Medical School, 2 Jalan Bukit Merah, Singapore. gmstanp@duke-nus.edu.sg
D000818:Animals; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*
Nat Genet. 2008 Jun;40(6):730-40
18488030
Br J Haematol. 2002 Jan;116(1):211-7
11841419
BMC Med. 2008 Sep 08;6:26
18778477
Nature. 2007 Jun 28;447(7148):1087-93
17529967
Nat Genet. 2003 May;34(1):23-4; author reply 25
12721549
Science. 2004 Jun 4;304(5676):1497-500
15118125
Cancer Cell. 2006 Apr;9(4):313-25
16616336
Clin Cancer Res. 2008 Jan 15;14(2):461-9
18223220
Nature. 2008 Apr 3;452(7187):633-7
18385738
Nature. 2005 Oct 27;437(7063):1299-320
16255080
Blood. 2006 Sep 15;108(6):2020-8
16728703
J Clin Oncol. 2006 Sep 20;24(27):4434-40
16983111
Cell. 2000 Jan 7;100(1):57-70
10647931
Nat Rev Genet. 2008 May;9(5):356-69
18398418
N Engl J Med. 2004 May 20;350(21):2129-39
15118073
N Engl J Med. 2002 Dec 19;347(25):1999-2009
12490681
J Clin Oncol. 2004 Apr 15;22(8):1382-8
15007088