Cancer risks in LKB1 germline mutation carriers.
OBJECTIVE
Germline mutations in the LKB1 gene are known to cause Peutz-Jeghers syndrome, which is an autosomal dominant disorder characterised by hamartomatous polyposis and mucocutaneous pigmentation. This syndrome is associated with an increased risk of malignancies in different organs but there is a lack of data on cancer range and risk in LKB1 germline mutation carriers.


METHODS
The cumulative incidence of cancer in 149 Peutz-Jeghers syndrome patients with germline mutation(s) in LKB1 was estimated using Kaplan-Meier time to cancer onset analyses and compared between relevant subgroups with log rank tests.


RESULTS
Thirty two cancers were found in LKB1 mutation carriers. Overall cancer risks at ages 30, 40, 50, 60, and 70 years were 6%, 18%, 31%, 41%, and 67%, respectively. There were similar overall cancer risks between male and female carriers. However, there were overall cancer risk differences for exon 6 mutation carriers versus non-exon 6 mutation carriers (log rank p=0.022 overall, 0.56 in males, 0.0000084 in females). Most (22/32) of the cancers occurred in the gastrointestinal tract, and the overall gastrointestinal cancer risks at ages 40, 50, 60, and 70 years were 12%, 24%, 34%, and 63%, respectively. In females, the risks for developing gynaecologic cancer at ages 40 and 50 years were 13% and 18%, respectively.


CONCLUSIONS
Mutations in exon 6 of LKB1 are associated with a higher cancer risk than mutations within other regions of the gene. Moreover, this study provides age related cumulative risks of developing cancer in LKB1 mutation carriers that should be useful for developing a tailor made cancer surveillance protocol for Peutz-Jeghers syndrome patients.
Mehenni
H
H
Unité de Gastroentérologie et Hépatologie, Centre Médico-chirurgical de Plainpalais et Département de Biologie Cellulaire, Université de Genève, Switzerland. mehenni@cellbio.unige.ch
Resta
N
N
Park
J-G
JG
Miyaki
M
M
Guanti
G
G
Costanza
M C
MC
D000091162:AMP-Activated Protein Kinase Kinases; D017677:Age Distribution; D001943:Breast Neoplasms / Q000235:genetics; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000235:genetics*; D010580:Peutz-Jeghers Syndrome / Q000150:complications / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018570:Risk Assessment; D017678:Sex Distribution
D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases