Resident Physician Cedars-Sinai Medical Center, Department of Surgery, Division of Urology
Introduction: Germline alterations have been identified in several types of cancer but are understudied in bladder cancer. However, recent studies have suggested that germline alterations may contribute to several cancers without known germline predispositions, including bladder cancer. We sought to evaluate the impact of bladder cancer germline alterations on age of disease onset. Methods: We queried a multi-institutional pan-cancer database of > 5 million patients for patients diagnosed with primary bladder cancer. Patients were categorized based on presence of germline alterations. Demographic factors and disease-specific factors were collected. Groups were compared to assess for statistical significance (p < 0.05). Average age of onset of bladder cancer was compared for patients with germline alterations with a sample of = 15 patients. Results: A total of 13,212 patients with primary bladder cancer were identified. Germline alterations were present in 465 (3.5%) patients. Patients with germline alterations did not significantly differ in gender distribution or smoking status compared to those without. Patients without germline alterations were more likely to identify as non-Hispanic (p=0.005) and white (p=0.027), and more likely to have Stage 4 disease (p < 0.0001). Mean age at diagnosis was 68.1 years in patients with germline alterations and 70 years in patients without (p < 0.001). Patients with germline alterations were more likely to be diagnosed between ages 50-59. A greater proportion of patients without germline alterations were diagnosed after age 80 (Figure 1a). The majority of individual genes surveyed were associated with earlier disease onset; the average age of onset was =65 in patients with alterations in APOB, MSH2, or TSC2 (Figure 1b). Conclusions: Germline alterations in patients with bladder cancer is significantly associated with younger age at time of diagnosis. This suggests germline alterations may have clinical impact on the age of onset of bladder cancer and should be further investigated as an impacting factor in assessing bladder cancer risk. Further studies are needed to evaluate the effect of specific genetic variants and whether these have implications for disease outcomes. SOURCE OF Funding: None
