HNPCC?????

1
HNPCC?????

• ??????????
• ????
• ???
• 2010-4-29

2
Contents
1.????
2.?????
3.?????
3
????
4
??????

• ??HNPCC?
• ????????? 5-10???MMR????
• ?????
• ??????MLH1?MSH2??????
• ????
• ???,???
• 90?????MLH1?MSH2
• ?????

5
??????

• ????
• Amsterdam IIIBethesda
• ???
• ???InSight (http//www.insight-group.org)
• ?????????
• ?????,??????
• ??????
• ??????????????
• ????????????

6
?????
7
?????
8
?????
9
?????
10
??

• ??gt??
• 64.7 vs. 35.3

11
Amsterdam III criteria Bethesda criteria All
n() 15(15.3) 83(84.7) 98(100)
Age(median, range)
years 48.1(35-67) 47.6(19-82) 47.7(19-82)
Sex n()
male 12(80.0) 45(54.2) 57(58.2)
female 3(20.0) 38(45.8) 41(41.8)
Location n()
Ascending colon 5(23.8) 20(20.4) 25(21.0)
Hepatic flexure 2(9.5) 2(2.0) 4(3.4)
Transverse colon 2(9.5) 8(8.2) 10(8.4)
Splenic flexure 2(9.5) 1(1.0) 3(2.5)
Descending colon 4(19.0) 8(8.2) 12(10.1)
Sigmoid colon 3(14.3) 15(15.3) 18(15.1)
Rectum 3(14.3) 44(44.9) 47(39.5)
Multiple cancer
synchronous tumours 3(20.0) 3(3.6) 6(6.1)
metachronous tumour 4(26.7) 17(20.5) 21(21.4)
Pathology
adenocarcinoma 13(86.7) 69(83.1) 82(83.7)
mucinous carcinoma 2(13.3) 11(13.2) 13(13.3)
Others 0(0.0) 3(3.6) 3(3.1)
Family history 15 51 66
??????????
????gt10
12
Family ID CRC number CRC frequency Cancer number Cancer frequency Male Female Onset age of CRC Onset age of cancer Multiple primary CRC Multiple primary tumors Right site Left site Extracolonic cancer (type) Mucinous carcinoma
H9 4 6 4 6 3 1 48 48 2 2 5 1 0 0
H76 5 5 5 5 4 1 37 37 0 0 1 4 0 0
H86 1 2 3 5 2 1 47 47 1 1 1 1 3(1St, 1Es, 1E) 1
H88 1 1 3 3 3 0 19 19 0 0 1 0 2(2L) 0
H166 4 5 4 5 2 2 36 36 1 1 2 3 0 0
H167 4 6 5 7 3 2 29 29 2 2 1 5 1(1E) 0
H224 1 1 5 7 2 3 44 51 0 2 0 1 6(2St, 2E, 2Br) 0
H231 1 1 2 3 1 1 47 44 0 1 0 1 2(1L, 1Br) 0
H236 3 3 3 4 1 2 40 40 0 1 0 3 1(1E) 1
H245 1 1 3 6 1 2 56 50 0 1 0 1 5(2St, 1Li, 1L, 1O) 0

• 31 CRC happened, 11 were left side and 20 were
  right (64.5 vs. 35.5),
• 20 related cancers happened, most of them were
  gastric cancer and endometrial carcinoma, 5 each
  (25).

13

• AC?15?,??4?
• ???????????,??30?,??8?
• ?????,????
• ??????

14
??
Family ID Mutation Mutation Mutation Mutation Mutation Clinical criteria Having been reported (times)
Family ID Gene Exon Nucleotide Consequence Type Clinical criteria Having been reported (times)
H9 MSH2 1 c.23CgtT p.Thr8Met Missense Amsterdam Yes (5)
H76 MLH1 2 c.157del GAGG Frameshift Amsterdam No
H86 MLH1 1 c.-64GgtT Uncertain Bethesda No
H88 MSH2 7 c.1168CgtT p.Phe390Leu Missense Bethesda Yes (34)
H166 MLH1 8 c.655AgtG p.Ile219Val Missense Amsterdam Yes (224)
H167 MLH1 17 c.1989GgtA Aberrant splicing Amsterdam Yes (2)
H224 MLH1 19 c.2159insG Frameshift Bethesda No
MSH2 7 c.1168CgtT p.Phe390Leu Missense Bethesda Yes (34)
H231 MSH2 7 c.1168CgtT p.Phe390Leu Missense Bethesda Yes (34)
H236 MLH1 18 c.2042CgtT p.Ala681Val Missense Bethesda Yes (1)
H245 MSH2 7 c.1168CgtT p.Phe390Leu Missense Bethesda Yes (34)
??????????,?????????
15

• ????????MSH2 c.1168CgtT
• InSight??????????????????
• ?????????? or SNP

16
????

• 1. Lee S-C, Guo J-Y, Lim R et al. Clinical and
  molecular characteristics of hereditary
  non-polyposis colorectal cancer families in
  Southeast Asia. Clinical Genetics 2005 68
  137-145.
• 2. Landis SH, Murray T, Bolden S et al. Cancer
  statistics, 1999. CA Cancer J Clin 1999 49
  8-31, 31.
• 3. Lynch HT, Smyrk T. Hereditary nonpolyposis
  colorectal cancer (Lynch syndrome) An updated
  review. Cancer 1996 78 1149-1167.
• 4. Ricciardiello L, Boland C. Lynch syndrome
  (hereditary non-polyposis colorectal cancer)
  Current concepts and approaches to management.
  Current Gastroenterology Reports 2005 7
  412-420.
• 5. Lynch HT, Lynch JF, Lynch PM. Toward a
  consensus in molecular diagnosis of hereditary
  nonpolyposis colorectal cancer (Lynch syndrome).
  J Natl Cancer Inst 2007 99 261-263.
• 6. Lynch HT, de la Chapelle A. Hereditary
  Colorectal Cancer. The New England Journal of
  Medicine 2003 348 919-932.
• 7. Vasen HFA, Watson P, Mecklin J-P et al. New
  clinical criteria for hereditary nonpolyposis
  colorectal cancer (HNPCC, Lynch syndrome)
  proposed by the International Collaborative Group
  on HNPCC. Gastroenterology 1999 116 1453-1456.
• 8. Lynch HT, de la Chapelle A. Genetic
  susceptibility to non-polyposis colorectal
  cancer. Journal of Medical Genetics 1999 36
  801-818.
• 9. Vasen HFA, Wijnen JT, Menko FH et al. Cancer
  risk in families with hereditary nonpolyposis
  colorectal cancer diagnosed by mutation analysis.
  Gastroenterology 1996 110 1020-1027.
• 10. Aarnio M, Mecklin J-P, Aaltonen LA et al.
  Life-time risk of different cancers in hereditary
  non-polyposis colorectal cancer (HNPCC) syndrome.
  International Journal of Cancer 1995 64
  430-433.
• ??????

17
Thank you!