Further observations on LKB1/STK11 status and cancer risk in Peutz–Jeghers syndrome

Abstract

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.

Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach

“…Inherited forms of gastrointestinal cancer have attracted the attention of scientists over the past two decades, putting the accent on prevention. The possibility of developing any cancer by age 65 years was 37% in accordance with data from the St. Mark's Polyposis Registry [52] . Hearle et al [53] have analyzed the incidence of cancer in 419 PJS patients, and 297 of them had documented STK11/LKB1 mutations.…”

“…It is necessary to perform consistent screening for possible malignancies in all patients with PJS: colonoscopy, upper endoscopy, CT, MRI or ultrasound of the pancreas, chest X-ray, mammography and pelvic examination with ultrasound in women, testicular examination in men, carbohydrate antigen 19-9 (CA-19-9), and cancer antigen (CA 125) [52][53][54][55] . DBE together with capsule endoscopy are essential modalities for the management of small intestinal diseases.…”

AMP-activated protein kinase and human cancer: cancer metabolism revisited

“…16 Women also have increased risk of both breast and cervical cancer. [16][17][18] With the advent of molecular biology, the search for a gene associated with the Peutz-Jegher syndrome culminated in 1998, with two papers that described a novel serine threonine kinase mutated in patients with the Peutz-Jegher syndrome. 19,20 Although the function of the gene was unknown, it was the first cancer susceptibility syndrome linked to inactivating mutations in a protein kinase.…”

Mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADα, and MO25α, in Peutz–Jeghers syndrome

“…However, 30 -82% of PJS patients have no detectable LKB1 mutations, suggesting locus heterogeneity (Lim et al, 2003, and references therein). Moreover, some families have been reported to be clearly unlinked to LKB1 locus (Mehenni et al, 1997;Olschwang et al, 1998).…”