Peutz-Jeghers Syndrome (PJS)

STK11 ASSOCIATED CANCER RISKS

 BREASTOVARIANGASTRICCOLORECTALPANCREATICMELANOMAPROSTATEENDOMETRIALOTHER

Additional Information

Associated Syndrome Name: Peutz-Jeghers Syndrome

STK11 Summary Cancer Risk Table

CANCER GENETIC CANCER RISK
Female Breast High Risk
Colorectal High Risk
Endometrial High Risk
Pancreatic High Risk
Gastric High Risk
Ovarian High Risk
Other High Risk

STK11 gene Overview

Peutz-Jeghers Syndrome 1, 2, 3, 4, 5

  • Individuals with mutations in the STK11 gene have a condition called Peutz-Jeghers Syndrome (PJS).
  • Women with PJS have a risk for breast cancer that is significantly increased over the 12.5% lifetime risk for women in the general population of the United States. Individuals with PJS have high risks for a variety of other cancers, including colorectal, endometrial, gastric, pancreatic, small bowel, cervical and lung cancers. These cancers are often diagnosed at relatively young ages.
  • The cervical cancer associated with PJS, adenoma malignum, which is also known as minimal deviation adenocarcinoma (MDA), may be difficult to diagnose.
  • Women with PJS have an increased risk for ovarian neoplasms, including adenocarcinomas. However, sex cord tumors are the most common ovarian tumor found in these patients.
  • Males with PJS have an increased risk for testicular tumors, particularly large cell calcifying Sertoli cell tumors (LCCSCT). These tumors have a low risk for malignancy, but if left untreated may lead to feminizing changes, advanced skeletal age and short stature.
  • Patients with PJS are likely to develop hamartomatous gastrointestinal polyps with a distinctive Peutz-Jeghers histology. The most common location of these polyps is the small bowel, but they may also be found in the stomach, colon and nasal passages. Polyps may require treatment due to bleeding with subsequent anemia, recurrent obstruction and/or intussusception.
  • Patients with PJS are likely to develop pigmented spots around the mouth, eyes, nostrils, anus and on the fingers during childhood. These spots are usually present by age 5 and often fade during puberty and adulthood.
  • Although there are high risks for cancer and other medical problems in patients with PJS syndrome, these risks can be reduced with appropriate medical management. Guidelines from the National Comprehensive Cancer Network (NCCN) are listed below, and additional detailed discussions of medical management options are also available from other sources (see van Lier MG et al., Am J Gastroenterol. 2010, 105:1258-64 and Beggs AD et al. Gut. 2010, 59:975-86). Due to the complexity of the condition it is recommended that patients with STK11 mutations and a diagnosis of PJS be managed by a multidisciplinary team with experience in the prevention and treatment of the complications associated with this condition.

STK11 gene Cancer Risk Table

CANCER TYPE AGE RANGE CANCER RISK RISK FOR GENERAL POPULATION *
Colorectal To age 702, 4 39% 1.9%
Pancreatic To age 702, 4 11%-36% 0.5%
Female Breast To age 704 45%-50% 7.3%
Gastric To age 702, 4 29% 0.3%
Small Bowel To age 702, 4 13% 0.1%
Ovarian To age 704 18%-21% 0.7%
Endometrial To age 702, 4 9% 1.6%
Cervical To age 702, 4 10% 0.5%
Testicular To age 702 Elevated risk 0.4%
Lung To age 702, 4 15%-17% 2.6%

STK11 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

CANCER TYPE PROCEDURE AGE TO BEGIN FREQUENCY
Colorectal Colonoscopy4 Late teens Every 2 to 3 years
Pancreatic Magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS).4, 9 30 to 35 years Every 1 to 2 years
Female Breast Clinical breast examination4 25 years Every 6 months
Mammography and breast MRI with contrast4, 8 25 years Annually
Gastric Upper endoscopy4, 7 Late teens Every 2 to 3 years
Small Bowel Small bowel visualization with CT or MRI enterography.4 Baseline at 8 to 10 years with follow up as needed, but no later than age 18 Every 2 to 3 years after age 18
Ovarian Pelvic examination4 18 to 20 years Annually
Consider transvaginal ultrasound.4 18 to 20 years Annually
Endometrial Pelvic examination4 18 to 20 years Annually
Consider transvaginal ultrasound.4 18 to 20 years Annually
Cervical Pap smear4 18 to 20 years Annually
Testicular Annual testicular examination and observation for feminizing changes.4 10 years Annually
Lung Provide education about symptoms and smoking cessation.4 As needed As needed

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the STK11 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

Since STK11 mutations carry a risk for complications in children and some screenings are recommended to begin by age 8, consideration should be given to the possibility of mutation testing in childhood.

There are reports of cases where individuals with a mutation in STK11 have not inherited the mutation from a parent. In these cases the mutation has developed spontaneously in that individual (a de novo mutation). Once this occurs, the children of that individual are each at 50% risk of inheriting the mutation.1

References

  1. McGarrity TJ, et al. Peutz-Jeghers Syndrome. 2016 Jul 14. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1266/ PMID: 20301443.
  2. van Lier MG, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010 105:1258-64. PMID: 20051941.
  3. Beggs AD, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010 59:975-86. PMID: 20581245.
  4. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at http://www.nccn.org.
  5. Banno K, et al. Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review). Oncol Lett. 2013 6:1184-1188. PMID: 24179492.
  6. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  7. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at http://www.nccn.org.
  8. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 1.2017. September 19. Available at http://www.nccn.org.
  9. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
Last Updated on 01-Jun-2017