Relative frequency and morphology of cancers in STK11 mutation carriers.
OBJECTIVE
There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS).


METHODS
We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11.


RESULTS
Fifty-four cancers were found among carriers. Overall, the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1%, 3%, 19%, 32%, 63%, and 81%, respectively. Kaplan-Meier analysis showed similar cancer risks between missense and truncating mutation carriers (log-rank chi(2) = 2.48; P = 0.12). There was some evidence that mutations in exon 3 of STK11 were associated with a higher cancer risk than mutations within other regions of the gene. We found no difference in overall cancer risk between male and female carriers (log-rank chi(2) = 1.31; P = 0.25) or between familial and sporadic cases (log-rank chi(2) = 1.16, with 1 df; P = 0.28). The most common cancers represented were gastrointestinal in origin--gastroesophageal, small bowel, colorectal, and pancreatic--and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 10%, 18%, and 42%, respectively. In women, the risk for breast cancer was substantially increased, being 32% by age 60 years.


CONCLUSIONS
These results quantitatively show the spectrum of cancer risk associated with STK11 germline mutations in the context of PJS and provide a valuable reference for defining surveillance regimens.
Lim
Wendy
W
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Olschwang
Sylviane
S
Keller
Josbert J
JJ
Westerman
Anne Marie
AM
Menko
Fred H
FH
Boardman
Lisa A
LA
Scott
Rodney J
RJ
Trimbath
Jill
J
Giardiello
Francis M
FM
Gruber
Stephen B
SB
Gille
Johan J P
JJ
Offerhaus
G Johan A
GJ
de Rooij
Felix W M
FW
Wilson
J H Paul
JH
Spigelman
Allan D
AD
Phillips
Robin K S
RK
Houlston
Richard S
RS
D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010190:Pancreatic Neoplasms / Q000453:epidemiology / 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