Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome.
Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.
Lim
W
W
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. wlim@icr.ac.uk
Hearle
N
N
Shah
B
B
Murday
V
V
Hodgson
S V
SV
Lucassen
A
A
Eccles
D
D
Talbot
I
I
Neale
K
K
Lim
A G
AG
O'Donohue
J
J
Donaldson
A
A
Macdonald
R C
RC
Young
I D
ID
Robinson
M H
MH
Lee
P W R
PW
Stoodley
B J
BJ
Tomlinson
I
I
Alderson
D
D
Holbrook
A G
AG
Vyas
S
S
Swarbrick
E T
ET
Lewis
A A M
AA
Phillips
R K S
RK
Houlston
R S
RS
D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010580:Peutz-Jeghers Syndrome / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases