S2096 PALB2 and the Risk for Colorectal Cancer

Abstract

Introduction: Colorectal cancer (CRC) is the most prevalent cancer in the gastrointestinal system and the third leading cause of cancer-related deaths in the United States. Hereditary factors play an important role in the risk of CRC and it has been estimated that up to 30% of CRC cases are affected by genetic factors. However, mutations in CRC-susceptibility genes explain less than 10% of CRC cases. Germline mutations in deoxyribonucleic acid (DNA)-repair genes have recently been reported more frequently in CRC. PALB2 is one such germline mutation that was recently evidenced as a CRC risk gene. We present a case of a female patient diagnosed with invasive sigmoid adenocarcinoma in the setting of no significant risk factors except for positive gene testing for PALB2. Case Description/Methods: A 32-year-old female with no significant past medical history presented with an episode of painless, large-volume bright red blood per rectum. She endorsed a 2-month history of intermittent rectal bleeding noted on wiping. Complete blood count revealed a microcytic anemia with hemoglobin of 8.4. Iron panel was consistent with anemia of chronic disease. Colonoscopy revealed a large, infiltrating and partially obstructing mass in the recto-sigmoid colon measuring 6 cm with evidence of mucosal bleeding. Biopsy confirmed invasive adenocarcinoma. Computed tomography (CT) of the abdomen showed multiple hypodense hepatic lesions suggestive of metastatic disease (Figure 1). Discussion: Mutations in PALB2 have been associated with an increased risk of familial cancers including breast, pancreatic, and gastric cancers. PALB2 encodes a protein that functions in tumor suppression and is primarily involved in the DNA repair process. PALB2 is altered in 2.8% of colorectal cancer cases. One study proved that PALB2 was an independent prognostic factor in CRC. Further studies on mutations involving PALB2 in CRC can help delineate a patient’s risk for malignancy and provide vital information for gastric cancer prevention. It will also allow for more personalized treatment options to have improved survival outcomes.Figure 1.: Malignant, partially obstructing tumor in the recto-sigmoid colon that was about 19 to 25 cm from the anal verge.