Hereditary Cancer Management APP

Cancer genetics is extremely complex, leading to a confusing array of management guidelines that can be hard for both patients and providers to follow.  We are building and testing an APP (Clinical Decision Support (CDS) Tool) to simplify the process of finding the guidelines that apply to a specific patient with a specific mutation who has a specific clinical situation..  Residents/students who participate can be involved in specific aspects that suit their interest, ranging from parsing human readable standards into machine readable rules to coding to analyzing the impact of the standards on patients in our clinic.  Projects will be assigned based on the interests of the student/ resident.

Management is based on the National Comprehensive Cancer Network (NCCN) guidelines, which have become more comprehensive and more complete over time. Below is a visual of the increased depth and complexity of the guidelines: 

Image showing the progress from the NCCN Management Guidelines for Pathogenic Variants from 2016 - 2021 with increases in guidelines for providers to understand.

According to the official journal of the National Comprehensive Cancer Network (NCCN) advances in cancer genetics, such as increased use of multigene panel testing, has transformed the clinical approach to testing at-risk patients and their families. Based on these rapid advances, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast and Ovarian (now Breast, Ovarian, and Pancreatic) have undergone some major revisions over the past few years. 

Our APP gives patient-specific recommendations based on the gene and the patient’s personal clinical issues and presents the information to the patient in a user-friendly way. 

Sample Patient 


MUSC Health Hereditary Cancer Clinic

Management for: 33 year old Female with a pathogenic variant in MLH1

Name: Test Patient 

Race: Caucasian or White

Personal History: None

Family History (Youngest Age): Ovary (age 45)

Date of genetic test: 01/01/2022

First person tested: Patient

Side of family affected: unknown


Summary of information about MLH1

The MLH1 gene is associated with autosomal dominant Lynch syndrome (also called hereditary nonpolyposis colorectal cancer syndrome, or HNPCC) (MedGen UID: 232603) and autosomal recessive constitutional mismatch repair deficiency syndrome (CMMR-D) (MedGen UID: 78553). MLH1-related Lynch syndrome is characterized by increased risk of various cancers including colorectal, endometrial, ovarian, urinary tract, gastrointestinal, brain and possibly prostate. Lifetime cancer risks include a 46–61% risk for colorectal cancer, a 5–7% risk for gastric cancer, a 6% risk for pancreatic cancer, up to an 11% risk for cancer of the small intestines, up to a 5% risk for urinary tract cancer, a 2–7% risk for bladder cancer, a 2–4% risk for cancer of the biliary tract and up to a 1.7% risk for brain/nervous system cancer. Affected females also have an increased risk of uterine/endometrial cancer (34-54%) and ovarian cancer (4–20%) (PMID: 21642682, 28754778, 28772289, 19900449, 26385421, 27013479, 18398828, 26657901,19900449, 31337882). CMMR-D is a cancer syndrome characterized by childhood malignancies, most commonly hematological malignancies and/or brain tumors, as well as very early-onset colorectal cancer. Nearly all affected individuals have clinical findings reminiscent of neurofibromatosis type 1 (NF1) such as cafe-au-lait spots (PMID: 18709565, 20442441, 17539897).

MLHI cancer risk for a 25 year old female up to age 85

MLH1 cancer risk for a 25 year old female up to age 85

Individualized management based on National Comprehensive Cancer Network (NCCN) guidelines as they apply to a 33 year old Female with a pathogenic variant in MLH1

Organ/Modality   Recommendation 
 Examination  Annual physical and neurologic examination is suggested due to her MLH1 mutation (There is a small increased risk of brain tumor.
 Chemoprevention  We discussed that taking two 325mg aspirins daily may help decrease the risk of colon polyps. The patient should consider taking 2 aspirin but if not tolerated, trying one per day. If this is tolerated, it is seems to be a good thing to do. If the patient notices stomach upset or other issues, they should stop.
 Imaging  We discussed that pancreatic cancer screening is not recommended at this time as there is no significant family history of pancreatic cancer.
 Dermatologic Exam  We discussed that skin exam every 1-2 years is recommended, due to the risk of sebaceous lesions, keratoacanthomas and other skin lesions.
 Symptom Education  We discussed that symptoms may include a mole or pigmented spot with: asymmetry; irregular, ragged, notched, or blurred borders; color that is not the same all over and may include shades of brown or black, sometimes with patches of pink red, white, or blue; diameter that is larger than a pencil eraser or a pea, although some can be smaller; changing in size/shape/color over the past few weeks or months; bleeding or itching; a spot that looks different from all of the other spots on your skin.
 Endoscopy  We recommend  Esophagogastroduodenoscopy (EGD) with random biopsy of the proximal and distal stomach for  H. pylori, autoimmune gastritis, and intestinal metaplasia every 3-5 years.
 Urinalysis  We discussed that urinary tract cancer is more common in Lynch Syndrome, and recommend yearly urinalysis and urine cytology.
 Cascade Testing  

We have reinforced the importance of having as many family members tested as possible. We stressed the importance of testing before pregnancy for any relatives planning children. Preimplantation genetic testing (PGT-M) and/or prenatal diagnosis may be an option.  We also discussed the need for partner testing to decrease the risk of the recessive condition, Constitutional Mismatch Repair Deficiency (CMMRD), in offspring if the relative is positive.

Constitutional Mismatch Repair Deficiency (CMMRD) is a childhood cancer predisposition syndrome characterized by four main tumor types (hematologic malignancies, brain/CNS tumors, colorectal tumors and multiple intestinal polyps), and other malignancies including embryonic tumors and rhabdomyosarcoma.

We are happy to see any of her relatives who live here and can help find care closer to home for those who live at a distance.

 Hereditary Cancer Clinic  

We will plan to follow the patient in the Hereditary Cancer Clinic to maximize guideline based care for the pathogenic variant in MLH1