Clinical factors associated with urinary tract cancer in individuals with Lynch syndrome
Menée aux Etats-Unis auprès de plus de 51 000 personnes (âge médian : 49 ans ; 79,3 % de femmes), cette étude identifie les facteurs cliniques associés à un risque de cancer des voies urinaires chez les porteurs d'un syndrome de Lynch
Background : Lynch syndrome (LS) 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 LS carriers are at highest UTC risk. Our aim was to identify clinical factors associated with UTC among LS carriers. Methods : The study population was a cohort of 52,758 consecutively-ascertained individuals undergoing LS 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 LS carriers. Results : Compared to non-carriers, LS carriers were significantly more likely to have had UTC (4.1% vs. 1.2%; P<0.0001). LS-associated UTC was independently associated with male sex (OR 1.95; 95% 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 1st/2nd-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 LS-associated malignancy. 143/158 (90.5%) LS carriers with UTC had ≥1 of the following characteristics: male sex, EPCAM/MSH2 variants, or family history of UTC; 1236/1251 (98.8%) LS carriers lacking all of these characteristics had no history of UTC. Conclusions : Specific clinical factors can reliably identify LS carriers most likely to be at risk for UTC. Impact : A predictable subset of LS carriers may be most likely to benefit from UTC surveillance/prevention.