title: Mismatch repair gene mutation analysis and colonoscopy surveillance in Chinese Lynch syndrome families.
abstract: BACKGROUND
  Lynch syndrome (or HNPCC) is a colorectal cancer syndrome caused by germline mutations in either one of the DNA mismatch repair (MMR) genes hMLH1, hMSH2, hMSH6 or hPMS2. Mutations in hMLH1 and hMSH2 are most prevalent. Here we aimed to determine the cancer risk of MMR gene mutation carriers and, in addition, the efficacy of colonoscopy surveillance in Chinese Lynch syndrome family members with and without MMR gene mutations.
  
  
  METHODS
  A Lynch syndrome family registry encompassing 106 families in Northern China was recently established. Detailed pedigree data for each family were collected and hMLH1 and hMSH2 gene mutation analyses were performed. Germ-line mutations were identified in probands from 42 of these families, and additional genetic analyses were performed in each member of these 42 families to identify mutation and non-mutation carriers. Among the family members included, 180 received colonoscopy and the remaining cases were followed without colonoscopy.
  
  
  RESULTS
  Overall 54.8 % of the Lynch syndrome family members carried MMR gene mutations, and these mutation carriers exhibited significantly higher colorectal cancer and other Lynch syndrome-associated cancer risks as compared to non-mutation carriers. The cumulative risk for all Lynch syndrome-related cancers at age 70 was 93.8 % for both hMLH1 and hMSH2 mutation carriers, and 81.7 % and 93.1 % for colorectal cancer at this age, respectively. Whereas 43 of 102 (42.2 %) mutation carriers exhibited significant colonoscopy findings, including 10 colorectal cancers, none of 78 non-mutation carriers exhibited significant findings, and no cancers were detected. In addition, in the mutation carriers, colonoscopy surveillance led to the detection of more early stage cancers than in the non-surveillance group (70.0 % versus 36.5 %, p < 0.01).
  
  
  CONCLUSIONS
  In Lynch syndrome family members, we recommend pre-symptomatic MMR gene mutation analysis in order to identify high risk individuals for colonoscopy surveillance.
authors: Department of Gastroenterology, Third Military Medical University and General Hospital of Beijing Military Region, Chongqing, 400038, China.
authors: Lei
authors: L
authors: Fu
authors: Jian-qiu
authors: JQ
authors: Sheng
authors: Xiao-ou
authors: XO
authors: Li
authors: Peng
authors: P
authors: Jin
authors: Hong
authors: H
authors: Mu
authors: Min
authors: M
authors: Han
authors: Ji-sheng
authors: JS
authors: Huang
authors: Zi-qin
authors: ZQ
authors: Sun
authors: Ai-qin
authors: AQ
authors: Li
authors: Zi-tao
authors: ZT
authors: Wu
authors: Shi-rong
authors: SR
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011159:Population Surveillance; D012307:Risk Factors
references: CA Cancer J Clin. 2006 Jul-Aug;56(4):213-25
references: 16870997
references: Gastroenterology. 2010 Jun;138(7):2300-6
references: 20206180
references: Gastroenterology. 2006 May;130(6):1872-85
references: 16697750
references: Fam Cancer. 2001;1(1):57-60
references: 14574017
references: J Med Genet. 2000 Sep;37(9):641-5
references: 10978352
references: World J Gastroenterol. 2005 Mar 14;11(10):1481-8
references: 15770724
references: Biochimie. 2002 Jan;84(1):27-47
references: 11900875
references: Fam Cancer. 2005;4(3):245-8
references: 16136385
references: Bull Cancer. 2011 Mar;98(3):323-36
references: 21459714
references: Semin Oncol. 2007 Oct;34(5):411-7
references: 17920896
references: Am J Gastroenterol. 2010 Aug;105(8):1851-60
references: 20354509
references: J Natl Cancer Inst. 1997 Dec 3;89(23):1758-62
references: 9392616
references: World J Gastroenterol. 2009 Feb 28;15(8):983-9
references: 19248199
references: Eur J Hum Genet. 2006 Apr;14(4):390-402
references: 16479259
references: Cancer. 1996 Sep 15;78(6):1149-67
references: 8826936
references: J Natl Cancer Inst. 2000 Sep 20;92(18):1517-22
references: 10995807
references: World J Gastroenterol. 2006 Aug 21;12(31):4943-50
references: 16937488
references: Colorectal Dis. 2009 Feb;11(2):126-30
references: 19143775
references: Cytogenet Genome Res. 2008;122(1):22-7
references: 18931482
references: Clin Gastroenterol Hepatol. 2010 Feb;8(2):174-82
references: 19835992
references: Am J Surg Pathol. 2009 Jan;33(1):126-33
references: 18830122
references: Hered Cancer Clin Pract. 2009 Dec 23;7(1):17
references: 20028567
references: Surg Oncol. 2007 Dec;16 Suppl 1:S11-5
references: 18023570
references: Am J Epidemiol. 2002 Nov 15;156(10):885-902
references: 12419761