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Supplementary Table 1 shows number of TAP cases per site

Prior small reports have postulated a link between gastrointestinal polyposis and childhood and young adulthood cancer (CYAC) treatment (therapy-associated polyposis; TAP), but this remains a poorly understood phenomenon. The aim of this study was to describe the phenotypic spectrum of TAP in a multi-institutional cohort. TAP cases were identified from eight high-risk cancer centers. Cases were defined as patients with ≥10 gastrointestinal polyps without known causative germline alteration or hereditary colorectal cancer predisposition syndrome who had a history of prior treatment with chemotherapy and/or radiotherapy for CYAC. A total of 34 TAP cases were included (original CYAC: 27 Hodgkin lymphoma, three neuroblastoma, one acute myeloid leukemia, one medulloblastoma, one nephroblastoma, and one non-Hodgkin lymphoma). Gastrointestinal polyposis was first detected at a median of 27 years (interquartile range, 20–33) after CYAC treatment. A total of 12 of 34 (35%) TAP cases had ≥50 colorectal polyps. A total of 32 of 34 (94%) had >1 histologic polyp type. A total of 25 of 34 (74%) had clinical features suggestive of ≥1 colorectal cancer predisposition syndrome [e.g., attenuated familial adenomatous polyposis (FAP), serrated polyposis syndrome, extracolonic manifestations of FAP, mismatch repair–deficient colorectal cancer, or hamartomatous polyposis] including 8 of 34 (24%) with features of multiple such syndromes. TAP is an apparently acquired phenomenon that should be considered in patients who develop significant polyposis without known causative germline alteration but who have had prior treatment for a CYAC. Patients with TAP have features that may mimic various hereditary colorectal cancer syndromes, suggesting multiple concurrent biologic mechanisms, and recognition of this diagnosis may have implications for cancer risk and screening.

Supplementary Table 3 shows types of surgical resection

Supplementary Table 2 shows individual case-level data (clinical history, genetic testing, secondary cancers)

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.

Background & Aims Lynch syndrome is the most common inherited cause of gastrointestinal cancer and increases risk for a variety of malignancies, including gastric cancer. We aimed to identify clinical factors associated with gastric cancer in carriers of germline variants causing Lynch syndrome. Methods We collected data from 52,758 consecutive individuals tested for genetic variants associated with Lynch syndrome from June 2006 through July 2013 at a commercial laboratory. We obtained clinical and demographic data, as well as information on personal and family histories of cancer (first- and second-degree relatives) from forms completed by ordering providers. We performed multivariate logistic regression to identify clinical factors associated with gastric cancer in carriers of mutations that cause Lynch syndrome (pathogenic mutations). Results After we excluded individuals with missing clinical data (n=1664) or with multiple pathogenic mutations (n=8), we analyzed data from 51,086 individuals. Of these, 3828 persons carried pathogenic mutations (1346 with mutations in MLH1 , 1639 with mutations in MSH2 , 670 with mutations in MSH6 , 145 with mutations in PMS2 , and 28 with mutations in EPCAM ). Of the 3828 carriers of pathogenic mutations, 41 (1.1%) had a previous gastric cancer and 350 (9.1%) had 1 or more first- or second-degree relatives with gastric cancer. In multivariate analysis, male sex (odds ratio [OR], 2.82; 95% CI, 1.48–5.38), older age (OR, 2.07 per 10 years; 95% CI, 1.64–2.61), mutations in MLH1 (OR, 6.53; 95% CI, 1.50–28.42) or MSH2 (OR, 5.23 compared to mutations in MSH6 , PMS2 , or EPCAM ; 95% CI, 1.21–22.71), and first-degree relative with gastric cancer (OR, 2.52; 95% CI, 1.42–4.45), but not second-degree relatives (OR, 1.12; 95% CI, 0.40–3.18) were independently associated with gastric among carriers of pathogenic mutations. Conclusions In an analysis of data from almost 4000 carriers of Lynch syndrome-associated mutations, we found history of gastric cancer to be independently associated with male sex, older age, mutations in MLH1 or MSH2 , and with having a first-degree relative with gastric cancer. These findings suggest that personalized, risk-stratified approaches to gastric cancer surveillance may be appropriate for individuals with Lynch syndrome-associated mutations.

1512Background: MGT will identify cancer susceptibility gene variants in 4-10% of unselected PC pts. Such data have prompted calls for universal GC and MGT of all PC pts, but the real-world benefit...

1517Background: LS is the one of the most common inherited causes of cancer and predisposes to a wide variety of cancers. UTCs (kidney, renal pelvis, ureter, and bladder cancer) are collectively th...