Clinical Factors Associated with Urinary Tract Cancer in Individuals with Lynch Syndrome

Abstract

Background: Lynch syndrome confers markedly increased risks of various malignancies, including urinary tract cancers (UTC; renal pelvis, ureter, bladder, and possibly kidney cancers). It is unknown how to determine which Lynch syndrome carriers are at highest UTC risk. Our aim was to identify clinical factors associated with UTC among Lynch syndrome carriers.

Methods: The study population was a cohort of 52,758 consecutively ascertained individuals undergoing Lynch syndrome testing at a commercial laboratory. Clinical data were obtained from test request forms completed by the ordering provider. Univariate analysis and multivariate logistic regression were performed to identify factors associated with UTC among Lynch syndrome carriers.

Results: Compared with noncarriers, Lynch syndrome carriers were significantly more likely to have had UTC (4.1% vs. 1.2%; P < 0.0001). Lynch syndrome-associated UTC was independently associated with male sex [OR 1.95; 95% confidence interval (CI), 1.38-2.76], increased age (OR 2.44 per 10 years; 95% CI, 2.11-2.82), familial burden of UTC (OR 2.69 per first-/second-degree relative with UTC; 95% CI, 1.99-3.63), and pathogenic EPCAM/MSH2 variants (OR 4.01; 95% CI, 2.39-6.72) but not MLH1 variants (OR 1.17; 95% CI, 0.63-2.17), race, or history of other Lynch syndrome-associated malignancy. A total of 143 of 158 (90.5%) Lynch syndrome carriers with UTC had ≥1 of the following characteristics: male sex, EPCAM/MSH2 variants, or family history of UTC; 1,236 of 1,251 (98.8%) Lynch syndrome carriers lacking all of these characteristics had no history of UTC.

Conclusions: Specific clinical factors can reliably identify Lynch syndrome carriers most likely to be at risk for UTC.

Impact: A predictable subset of Lynch syndrome carriers may be most likely to benefit from UTC surveillance/prevention.