Preliminaries: Note on conventions Basic homotopy notions Surgery below the middle dimension Appendix: Applications Simple Poincare complexes The main theorem: Statement of results An important special case The even-dimensional case The odd-dimensional case The bounded odd-dimensional case The bounded even-dimensional case Completion of the proof Patterns of application: Manifold structures on Poincare complexes Applications to submanifolds Submanifolds: Other techniques Separating submanifolds Two-sided submanifolds One-sided submanifolds Calculations and applications: Calculations: Surgery obstruction groups Calculations: The surgery obstructions Applications: Free actions on spheres General remarks An extension of the Atiyah-Singer $G$-signature theorem Free actions of $S^1$ Fake projective spaces (real) Fake lens spaces Applications: Free uniform actions on euclidean space Fake tori Polycyclic groups Applications to 4-manifolds Postscript: Further ideas and suggestions: Recent work Function space methods Topological manifolds Poincare embeddings Homotopy and simple homotopy Further calculations Sullivan's results Reformulations of the algebra Rational surgery References Index.

Surgery on compact manifolds

Excessive incidence of various cancers is a challenging feature of the hereditary-non-polyposis-colorectal-cancer (HNPCC) syndrome. This study estimated the cancer incidences in HNPCC compared with the general population. Individuals in a cohort of 1763 members of 50 genetically diagnosed families were categorized according to their genetic status as mutation carriers, non-carriers, or individuals at 50 or 25% risk of being a carrier. Incidences of cancers in these groups were compared with those in the Finnish population overall. In 360 mutation carriers, standardized incidence ratios (SIR) were significantly increased for colorectal [68; 95% confidence intervals (CI), 56 to 81], endometrial (62; 95% CI, 44 to 86), ovarian (13; 95% CI, 5.3 to 25), gastric (6.9; 95% CI, 3.6 to 12), biliary tract (9.1; 95% CI, 1.1 to 33), uro-epithelial (7.6; 95% CI, 2.5 to 18) and kidney (4.7; 95% CI, 1 to 14) cancers and for central-nervous-system tumours (4.5; 95% CI, 1.2 to 12). The SIR increased with increasing likelihood of being a mutation carrier. The cumulative cancer incidences were 82, 60, 13 and 12% for colorectal, endometrial, gastric and ovarian cancers respectively. For other tumours associated with increased risk, corresponding incidences were below 4%. Interestingly, the incidence of endometrial cancer (60%) exceeded that for colorectal cancer in women (54%). The tumour spectrum associated with germline mutations of DNA-mismatch-repair genes involves 8 or more organ sites, suggesting a need to develop methods to screen for extra-colonic cancer also. Int. J. Cancer 81:214–218, 1999. © 1999 Wiley-Liss, Inc.

Cancer risk in mutation carriers of DNA-mismatch-repair genes.

https://www.gastrojournal.org/article/0016-5085(93)90368-M/pdf

Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: An updated review

Published studies of families with hereditary nonpolyposis colorectal cancer (HNPCC) frequently report the occurrence of cancers at extracolonic sites. Our purpose in this study was to compare the observed frequency of cancer at specific sites in members of 18 unrelated HNPCC kindreds with expectations based on general population incidence in order to determine whether there were specific types of cancer for which family members were at elevated risk. We were able to stratify family members according to their risk of carrying the putative HNPCC gene. We found that putative HNPCC gene carriers and their high risk relatives have been diagnosed with cancers other than uterine and colorectal more frequently than expected based on general population incidence figures. Specific sites where elevations are seen include the stomach, small intestine, biliary system (especially the bile ducts), urological system (especially the kidney and ureter), and ovary.

Extracolonic Cancer in Hereditary Nonpolyposis Colorectal Cancer

Identification of hereditary non-polyposis colorectal cancer (HNPCC) indicates theoretical life-time risks of 50% for the descendants of an affected family member and of 100% for the true gene carriers. However, besides colorectal cancer (CRC), many other cancer types and sites are also involved, which gives reason to evaluate the magnitude of risk for various other cancer types. A detailed pedigree analysis of 40 families with HNPCC identified 414 patients affected with cancer. A Kaplan-Meier life-table analysis for the cumulative risk of various cancers was performed on the basis of the 293 putative gene carriers who had adequate clinical and histological documentation of their tumors. Cumulative risks were highest for colorectal (78%) and endometrial cancers (43%, women only), followed by gastric, biliary tract, urinary tract and ovarian cancers (19-9%). For the other probably HNPCC-related cancer types, such as small bowel carcinoma and brain tumors, the life-time risk was only 1%. The risk of any metachronous cancer reached 90% after treatment of CRC and 75% after endometrial cancer; the second tumor was most often a new CRC or endometrial cancer. CRC remains the most important cancer type in the HNPCC syndrome but does not develop in all gene carriers. This makes the decision of possible prophylactic colectomy for test-detected gene carriers difficult. Of the many other cancer types involved, at least endometrial cancer is common enough to necessitate a specific surveillance program. © 1995 Wiley-Liss, Inc.

Life‐time risk of different cancers in hereditary non‐polyposis colorectal cancer (hnpcc) syndrome

To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes. In female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3.7. A screening programme based on estimated risks could be offered to first-degree relatives of index patients with Lynch type II cancer family syndrome.

Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom.

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Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom.