| 20 21 | See page 67 for references Cancer risks The following table breaks down the different cancers associated with CDH1. Cancer Lifetime risk Gastric cancer (men) 67%–70% Gastric cancer (women) 56%–83% Breast cancer (lobular) 39%–52% Colorectal Unknown Information in table from (1) Hansford et al (2015), (2) Kaurah et al (2002, updated 2014). Potential management options The general recommendation is to manage patients at centers with multidisciplinary expertise in HDGC and a multidisciplinary team, including a surgeon specializing in upper gastrointestinal surgery, a gastroenterologist, a nutritionist, a genetics expert, and a counselor or psychiatrist. NCCN recommends the following for individuals with CDH1 mutations: · ·Conduct baseline endoscopy with multiple random biopsies prior to gastrectomy; repeat every 6–12 months (for those patients who elect not to undergo prophylactic gastrectomy). · ·For families with a known history of diffuse gastric cancer, and meeting clinical criteria, perform prophylactic gastrectomy between 18 and 40 years. While surgery prior to age 18 is not recommended, consider surgery in families with a history of HDGC prior to age 25. · ·In families with a history of colon cancer, initiate colonoscopy screening at age 40 or sooner, repeating every 3 to 5 years or as medically necessary. · ·For women, perform mammography and consider breast MRI once a year, and clinical breast exams every 6 months beginning at age 30 or sooner, based on family history. Women may also consider prophylactic mastectomy based on family history. CDKN2A and CDK4 gene summary Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome Gene name CDKN2A/CDK4 Associated syndrome Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome Primary associated cancers Melanoma, pancreatic Frequency Unknown Inheritance pattern Autosomal dominant Overview · ·CDKN2A was the first gene associated with familial melanoma and is attributed to 20%–40% of familial melanoma cases. · ·CDKN2A has two biologically active transcripts, p14 and p16. Most of the cancer risk information published is for the p16 transcript. · ·Patients with FAMMM syndrome develop melanoma at a younger age and are at higher risk to develop a second primary melanoma compared to the general population. About Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome FAMMM syndrome may also be referred to as Familial Atypical Multiple Mole Melanoma- Pancreatic Carcinoma (FAMMM-PC) syndrome. FAMMM is characterized by increased risks for melanoma and pancreatic cancer. CDKN2A and CDK4 are tumor suppressor genes that function in cell cycle regulation. CDK4 has only two mutations described in hereditary melanoma families, both at codon 24, which is critical for allowing CDKN2A to bind to CDK4. The main clinical features of FAMMM syndrome include the following: · ·Multiple primary melanomas in the same individual, often with an early age of onset · ·Melanoma observed in multiple family members · ·High total body nevi count (often >50) · ·In some patients, atypical nevi: size >5 mm in diameter, border or contour irregularity, and pigmentation irregularities