Patient Clinical Profile

  • Patient Age: 23
  • Gender: Female
  • Personal Clinical History: No personal history of cancer or colon polyps.
  • Visit type: Irregular Heavy Vaginal Bleeding
    • * No prior history of bleeding problems
    • * Bleeding is impacting the patient’s life and she is seeking medical intervention

Myriad myRisk® Panel Test Result:



Colorectal cancer (CRC) remains one of the top three most deadly cancers in the United States.1 It also impacts both men and women equally, with the general population at approximately 4% lifetime risk of developing this disease.2 Recent evidence has revealed that approximately 10% of CRC is associated with pathogenic inherited genetic mutations.3 Patients with hereditary predisposition to CRC face a much higher risk of developing CRC compared to those at general population risk, with risks as high as up to 99%.4

The good news is most CRC can be caught early and at a treatable stage. Screening for CRC, including hereditary risk assessment and testing, is the one way to correctly stratify a patient’s hereditary cancer risk: “Early identification of mutation carriers allow prevention of most Lynch syndrome-associated malignancies.”5 Many families with Lynch syndrome (the most common hereditary CRC syndrome) may not show a distinctive phenotype.6 Therefore, genetic testing is the only way to correctly diagnose patients who actually have Lynch Syndrome, as highlighted in this case study.

Mutations in the PMS2 gene are associated with the following:

  • High risk for CRC, up to 20% by the age of 70 7,8
  • High risk for endometrial cancer, up to 15% by the age of 707,8
  • Elevated risk for Lynch syndrome-associated cancers, including: pancreatic, ovarian, gastric, small bowel, urinary tract, hepatobiliary tract, central nervous system, & sebaceous neoplasms9

Patient’s Family History

Relative Cancer Age of Dx
Paternal Great Grandmother Breast 48
Paternal Aunt Breast 55
Paternal Cousin Breast 35
Maternal Aunt Lung 68

After reviewing this patient’s symptoms and family history, her ObGyn was concerned with the multiple occurrences of breast cancer on her father’s side of the family. Not only is there a cluster of cancer, the young ages of onset are also alarming. A Myriad myRisk® Hereditary Cancer test was ordered to rule out any hereditary causes.

PMS2 Cancer Risk Management Table

  • Colonoscopy every 1 to 2 years beginning at age 20 to 25 years, or 2 to 5 years younger than the earliest diagnosis in family if it is under age 25 10,11
  • Consider the use of aspirin as a risk reduction agent 10,11
  • Colorectal surgical evaluation may be appropriate for some patients10
  • Consider annual pelvic examination, endometrial sampling and transvaginal ultrasound beginning at age 30 to 35 years 10,11
  • Consider hysterectomy after completion of childbearing 10,11
  • Consider bilateral salpingo-oophorectomy at age 40 or after completion of childbearing 10,11
  • Consider transvaginal ultrasound and CA-125 measurement beginning at age 30-35 years 10,11
  • Treat for Helicobacter pylori infection if present8
  • Consider upper endoscopy every 2 to 5 years, beginning at ages 30 to 35 years, particularly for patients with additional risk factors for gastric cancer, such as family history or Asian ancestry. Consider biopsy of the antrum 10,11,12
Small Bowel
  • Consider upper endoscopy beginning at age 30-35 years, particularly for patients with additional risk factors for small bowel cancer, such as family history10,11
Urinary Tract
  • Consider urinalysis annually beginning at age 30-35 years10,11
  • Consider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols13
Central nervous System
  • Annual physical/neurological examination beginning at age 25-30 years10

Bottom Line

This case demonstrates the importance of a diagnostic test to stratify a patient’s risk to develop cancer and to modify their future management appropriately. If the clinician followed a narrow approach by ordering only a BRCA test suspecting only Hereditary Breast and Ovarian cancer syndrome, this PMS2 mutation would have been missed and the patient’s risk for cancer unidentified. Instead of following the common options of immediately recommending an IUD or other hormonal options, the clinician may now consider additional screening in the future including transvaginal ultrasound, or endometrial sampling as part her future management at the appropriate age in light of her Lynch syndrome diagnosis and increased risk to develop endometrial cancer.

  1. Without this result, this patient would not have known that she is at risk for cancers other than those seen in her family history.
  2. The patient is now able to take the necessary medical management steps, which could include increased surveillance, risk-reduction agents, and surgery to prevent cancer from developing.
  3. She will begin screening for CRC with her first colonoscopy by age 25 rather than waiting until the age of 50, which is the recommended age to begin for the general population without CRC family history.
  4. It was important to capture and actively use both her maternal and paternal cancer family history.

Utilize our Cancer Family History Tool to screen and identify patients at increased cancer risk.

Get Your Custom Family History Tool Now



  1. Colon Cancer Alliance. Last accessed 1.28.2017.
  2. American Cancer Society. Lifetime risk of colorectal cancer. Last accessed 1.28.2017.
  3. Yurgelun, Matthew B et al, Prevalence of Germline Cancer Susceptibility Gene Mutations in a Clinic-Based Series of Colorectal Cancer Patients, Abstract # 1501 presented at ASCO 2016.
  4. Jasperson, Kory & Burt, Randall, APC-Associated Polyposis Conditions. Last Update: March 27, 2014. GeneReviews®. Last accessed 1.31.2017.
  5., Last accessed 1.28.2017
  6. ACOG Practice Bulletin: Lynch Syndrome, No. 147, Nov. 2014; 124: 1042-54
  7. Kerber, et al. Frequency of familial colon cancer and hereditary nonpolyposis colorectal cancer (Lynch syndrome) in a large population database. Familial Cancer 2005; 4:239-244
  8. Senter L, et al. The clinical phenotype of Lynch syndrome due to germline PMS2 mutations. Gastroenterology. 2008 135419-28.
  9. Broeke SW, et al. Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk. J Clin Oncol. 2015 33:319-25.
  10. PMS2 Gene. For a complete list of cancer risks related to PMS2, https:///gene-results/?gene=PMS2&allele=1. Last accessed 1.28.2017
  11. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at
  12. Giardiello FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2014 109:1159-79.
  13. Ajani JA, et al. NCCN Clinical Practice Guidelines in Oncology®: Gastric Cancer. V 3.2016. August 3. Available at
  14. 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.

Leave a Reply

Your email address will not be published. Required fields are marked *