The broad, long-term objective is to reduce morbidity and mortality caused by tumors occurring in the HNPCC syndrome. The first task is to define the natural history of HNPCC (e.g. age-dependent risk, spectrum of affected organs, clinical behavior) and the effect of predictive testing on clinical screening and preventive measures. his can be done by determining who is a carrier and who is not among as many as 288 affected and 1169 unaffected at-risk members of 81 previously diagnosed HNPCC families. The frequency of HNPCC will be determined by studying one-fourth of all colorectal carcinomas and adenomas removed in Finland. These will be screened for the replication error (RER) phenomenon that is indicative of, but not specific for, HNPCC. Individuals with RER-positive tumors will be screened for HNPCC mutations. This study will comprise some 2500 individuals annually. As there are almost no established procedures for the handling of data regarding individual susceptibility to a common, adult-onset cancer, the ethical and social aspects of this experiment in predictive testing will be researched by means of repeated individual counseling and evaluation, as well as by attempting to inform the medical profession, to educate the public, and to provide expertise to lawmakers.
| Le, Dung T; Durham, Jennifer N; Smith, Kellie N et al. (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357:409-413 |
| Haraldsdottir, Sigurdis; Hampel, Heather; Wu, Christina et al. (2016) Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses. Genet Med 18:863-8 |
| Goodenberger, McKinsey L; Thomas, Brittany C; Riegert-Johnson, Douglas et al. (2016) PMS2 monoallelic mutation carriers: the known unknown. Genet Med 18:13-9 |
| Le, Dung T; Uram, Jennifer N; Wang, Hao et al. (2015) PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372:2509-20 |
| Haraldsdottir, Sigurdis; Hampel, Heather; Tomsic, Jerneja et al. (2014) Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology 147:1308-1316.e1 |
| Pasche, Boris; Pennison, Michael J; Jimenez, Hugo et al. (2014) TGFBR1 and cancer susceptibility. Trans Am Clin Climatol Assoc 125:300-12 |
| Hampel, Heather; de la Chapelle, Albert (2013) How do we approach the goal of identifying everybody with Lynch syndrome? Fam Cancer 12:313-7 |
| Tomsic, J; Senter, L; Liyanarachchi, S et al. (2013) Recurrent and founder mutations in the PMS2 gene. Clin Genet 83:238-43 |
| Moreira, Leticia; Balaguer, Francesc; Lindor, Noralane et al. (2012) Identification of Lynch syndrome among patients with colorectal cancer. JAMA 308:1555-65 |
| Mercado, Rowena C; Hampel, Heather; Kastrinos, Fay et al. (2012) Performance of PREMM(1,2,6), MMRpredict, and MMRpro in detecting Lynch syndrome among endometrial cancer cases. Genet Med 14:670-80 |
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