Goecke, Timm and Schulmann, Karsten and Engel, Christoph and Holinski-Feder, Elke and Pagenstecher, Constanze and Schackert, Hans K. and Kloor, Matthias and Kunstmann, Erdmute and Vogelsang, Holger and Keller, Gisela and Dietmaier, Wolfgang and Mangold, Elisabeth and Friedrichs, Nicolaus and Propping, Peter and Krueger, Stefan and Gebert, Johannes and Schmiegel, Wolff and Rueschoff, Josef and Loeffler, Markus and Moeslein, Gabriela (2006) Genotype-phenotype comparison of German MLH1 and MSH2 mutation carriers clinically affected with lynch syndrome: A report by the German HNPCC Consortium. JOURNAL OF CLINICAL ONCOLOGY, 24 (26). pp. 4285-4292. ISSN 0732-183X,
Full text not available from this repository. (Request a copy)Abstract
Purpose Lynch syndrome is linked to germline mutations in mismatch repair genes. We analyzed the genotype-phenotype correlations in the largest cohort so far reported. Patients and Methods Following standard algorithms, we identified 281 of 574 unrelated families with deleterious germline mutations in MLH1 (n = 124) or MSH2 (n = 157). A total of 988 patients with 1,381 cancers were included in this analysis. Results We identified 181 and 259 individuals with proven or obligatory and 254 and 294 with assumed MLH1 and MSH2 mutations, respectively. Age at diagnosis was younger both in regard to first cancer (40 v 43 years; P <.009) and to first colorectal cancer (CRC; 41 v 44 years; P =.004) in MLH1 (n = 435) versus MSH2 (n = 553) mutation carriers. In both groups, rectal cancers were remarkably frequent, and the time span between first and second CRC was smaller if the first primary occurred left sided. Gastric cancer was the third most frequent malignancy occurring without a similarly affected relative in most cases. All prostate cancers occurred in MSH2 mutation carriers. Conclusion The proportion of rectal cancers and shorter time span to metachronous cancers indicates the need for a defined treatment strategy for primary rectal cancers in hereditary nonpolyposis colorectal cancer patients. Male MLH1 mutation carriers require earlier colonoscopy beginning at age 20 years. We propose regular gastric surveillance starting at age 35 years, regardless of the familial occurrence of this cancer. The association of prostate cancer with MSH2 mutations should be taken into consideration both for clinical and genetic counseling practice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONPOLYPOSIS COLORECTAL-CANCER; DNA-MISMATCH-REPAIR; MUIR-TORRE-SYNDROME; COLON-CANCER; TUMOR SPECTRUM; GENE-MUTATIONS; UNITED-STATES; SYNDROME-II; FAMILIES; RISK; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Feb 2021 08:05 |
| Last Modified: | 01 Feb 2021 08:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34033 |
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