title: Familial chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Families with multiple individuals affected with chronic lymphocytic leukemia (CLL) and other related B-cell tumors have been described in the literature and strong familial aggregation has been seen in population studies. However, predisposing germline mutations have not been identified. We will discuss the spectrum of conditions associated with CLL in families and the advances in identifying the underlying susceptibility genes.
  
  
  RESULTS
  Familial CLL does not appear to differ substantially from sporadic CLL in terms of prognostic markers and clinical outcome, although it may be associated with more indolent disease. The precursor condition, monoclonal B-cell lymphocytosis, also aggregates in CLL families. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for susceptibility loci but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated several genes as being important in CLL but more studies are needed. Results from whole-genome association studies are promising.
  
  
  CONCLUSIONS
  The ability to conduct large-scale genomic studies in unrelated CLL patients and in high-risk CLL families will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate causal pathways.
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892-7236, USA. goldinl@mail.nih.gov
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldin
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
mesh_terms: D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D018095:Germ-Line Mutation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D010375:Pedigree
references.citation: Leuk Res. 2003 Oct;27(10):871-6
references.pmid: 12860003
references.citation: Blood. 2002 Jul 15;100(2):635-9
references.pmid: 12091358
references.citation: Blood. 2004 Mar 15;103(6):2337-42
references.pmid: 14630808
references.citation: Nat Genet. 2008 Oct;40(10):1204-10
references.pmid: 18758461
references.citation: Blood. 2004 Sep 15;104(6):1850-4
references.pmid: 15161669
references.citation: Br J Haematol. 2009 Nov;147(3):339-46
references.pmid: 19709083
references.citation: Br J Haematol. 2007 Dec;139(5):701-8
references.pmid: 18021084
references.citation: Cytometry B Clin Cytom. 2003 Mar;52(1):1-12
references.pmid: 12599176
references.citation: Am J Epidemiol. 2009 Sep 15;170(6):671-8
references.pmid: 19700502
references.citation: Nat Genet. 2010 Feb;42(2):132-6
references.pmid: 20062064
references.citation: Blood. 2007 Nov 1;110(9):3326-33
references.pmid: 17687107
references.citation: Br J Haematol. 2007 Dec;139(5):762-71
references.pmid: 18021089
references.citation: Blood. 2007 Feb 1;109(3):916-25
references.pmid: 17047154
references.citation: Am J Hum Genet. 1999 Jul;65(1):265-9
references.pmid: 10364544
references.citation: Cell. 2007 Jun 1;129(5):879-90
references.pmid: 17540169
references.citation: Leukemia. 2010 Jan;24(1):133-40
references.pmid: 19946263
references.citation: Blood. 2008 Jun 15;111(12):5691-3
references.pmid: 18424666
references.citation: N Engl J Med. 2008 Aug 7;359(6):575-83
references.pmid: 18687638
references.citation: N Engl J Med. 2009 Feb 12;360(7):659-67
references.pmid: 19213679
references.citation: Blood. 2009 Jul 2;114(1):33-7
references.pmid: 19420353
references.citation: Br J Haematol. 2007 Dec;139(5):672-86
references.pmid: 18021081
references.citation: Cancer. 2004 May 1;100(9):1902-8
references.pmid: 15112271
references.citation: Haematologica. 2006 Aug;91(8):1117-20
references.pmid: 16885053
references.citation: Cancer Causes Control. 2002 Nov;13(9):791-5
references.pmid: 12462543
references.citation: CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
references.pmid: 19474385
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):1098-102
references.pmid: 20332261
references.citation: Leuk Res. 2002 Sep;26(9):791-4
references.pmid: 12127552
references.citation: Br J Haematol. 2009 Jun;146(1):91-4
references.pmid: 19438470
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):945-53
references.pmid: 19240243
references.citation: Br J Haematol. 2005 Aug;130(3):325-32
references.pmid: 16042682
references.citation: Blood. 2009 Jul 2;114(1):26-32
references.pmid: 19029437
references.citation: Br J Haematol. 2007 Dec;139(5):824-31
references.pmid: 18021093
references.citation: Blood. 2008 Jun 15;111(12):5446-56
references.pmid: 18216293
references.citation: N Engl J Med. 2005 Oct 27;353(17):1793-801
references.pmid: 16251535
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2402-6
references.pmid: 16214923
references.citation: Leuk Res. 2009 Jan;33(1):162-5
references.pmid: 18556064
references.citation: Blood. 2002 Oct 1;100(7):2289-90
references.pmid: 12239136
references.citation: Leuk Lymphoma. 2001 Jun;42(1-2):99-108
references.pmid: 11699227
references.citation: J Clin Oncol. 2009 Aug 20;27(24):3959-63
references.pmid: 19620484
references.citation: Blood. 2007 Apr 15;109(8):3479-88
references.pmid: 17185468
references.citation: Blood. 2009 Jul 23;114(4):791-5
references.pmid: 19182202
references.citation: Blood. 2008 Dec 1;112(12):4384-99
references.pmid: 19029456
references.citation: Int J Cancer. 2006 Jun 15;118(12):3095-8
references.pmid: 16395700
references.citation: Blood. 2008 Oct 15;112(8):3052-6
references.pmid: 18703425
references.citation: Haematologica. 2009 May;94(5):647-53
references.pmid: 19286886
references.citation: Nat Genet. 2009 Aug;41(8):873-5
references.pmid: 19620980
references.citation: Blood. 2009 Sep 24;114(13):2848-9
references.pmid: 19779049
references.citation: Curr Drug Targets. 2006 Oct;7(10):1313-27
references.pmid: 17073593
references.citation: Cancer Res. 2008 Dec 15;68(24):10178-86
references.pmid: 19074885
references.citation: Ann Hum Genet. 2004 Sep;68(Pt 5):498-508
references.pmid: 15469426
references.citation: J Clin Oncol. 2006 Feb 20;24(6):983-7
references.pmid: 16432079
references.citation: Leuk Lymphoma. 2007 Jun;48(6):1087-91
references.pmid: 17577771