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87 results on '"Lynch, H.T."'

3. An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome

Author

Jaeger, E.E.M., Woodford-Richens, K.L., Lockett, M., Rowan, A.J. Sawyer, E.J., Heinimann, K., Rozen, P., Murday, V.A., Whitelaw, S.C., Ginsberg, A., Atkin, W.S., Lynch, H.T., Southey, M.C., Debinski, H., Eng, C., Bodmer, W.F., Talbot, I.C., Hodgson, S.V., Thomas, H.J.W., and Tomlinson, I.P.M.

Subjects
Polyposis, Familial -- Risk factors, Polyposis, Familial -- Genetic aspects, Genetic disorders -- Research, Ashkenazim -- Genetic aspects, Haplotypes -- Research, Chromosome mapping -- Research, Biological sciences
Published
2003

5. Prevention of colorectal cancer: guidelines based on new data

Author

Winawer, S.J., St. John, D.J., Bond, J.H., Rozen, P., Burt, R.W., Wayne, J.D., Kronborg, O., O'Brien, M.J., Bishop, D.T., Kurtz, R.C., Shike, M., Swaroop, S.V., Levin, B., Fruhmorgen, P., and Lynch, H.T.

Subjects
World Health Organization -- Standards, Colorectal cancer -- Prevention, Medicine, Preventive -- Standards
Abstract

Recently published good quality data are the basis for this update. The newly reported studies include randomized trials, non-randomized cohort studies, and case-control studies; some of the data had mortality reduction as the endpoint. These guidelines, which were developed by the WHO Collaborating Center for the Prevention of Colorectal Cancer at Memorial Sloan-Kettering Cancer Center in conjunction with an International Advisory Committee, include primary prevention, screening of average-risk individuals, screening of individuals with heritable factors for colorectal cancer, surveillance of patients with colorectal polyps, and surveillance of patients with chronic ulcerative colitis. A list of papers reviewed for this update are cited, including recently published trials evaluating faecal occult-blood testing, case-control studies of sigmoidoscopy, the National Polyp study, and familial colon cancer studies. These guidelines will help inform patients and guide physicians in their approach to the prevention of colorectal cancer., Introduction This update of the WHO working guidelines for the prevention of colorectal cancer is based on current clinical and statistical information and may change as new data become available. [...]

Published
1995

6. Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

Author

Jernstrom, H., Lubinski, J., Lynch, H.T., Ghadirian, P., Neuhausen, S., Isaacs, C., Weber, B.L., Horsman, D., Rosen, B., Foulkes, W.D., Friedman, E., Gershoni-Baruch, R., Ainsworth, P., Daly, M., Garber, J., Olsson, H., Sun, P., and Narod, S.A.

Subjects
Breast feeding -- Influence, Breast feeding -- Case studies, Breast cancer -- Risk factors, Breast cancer -- Case studies, Health
Abstract

Background: Several studies have reported that the risk of breast cancer decreases with increasing duration of breastfeeding. Whether breast-feeding is associated with a reduced risk of hereditary breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations is currently unknown. Methods: We conducted a case--control study of women with deleterious mutations in either the BRCA1 or the BRCA2 gene. Study participants, drawn from an international cohort, were matched on the basis of BRCA mutation (BRCA1 [n = 685] or BRCA2 [n = 280]), year of birth ([+ or -] 2 years), and country of residence. The study involved 965 case subjects diagnosed with breast cancer and 965 control subjects who had no history of breast or ovarian cancer. Information on pregnancies and breast-feeding practices was derived from a questionnaire administered to the women during the course of genetic counseling. Conditional logistic regression analyses were used to estimate odds ratios (ORs) for the risk of breast cancer. All statistical tests were two-sided. Results: Among women with BRCA1 mutations, the mean total duration of breast-feeding was statistically significantly shorter for case subjects than for control subjects (6.0 versus 8.7 months, respectively; mean difference = 2.7 months, 95% confidence interval [CI] = 1.4 to 4.0; P

Published
2004

8. Risk and surveillance of individuals with heritable factors for colorectal cancer

Author

Burt, R.W., Bishop, H.T., Lynch, H.T., Rozen, P., and Winawer, S.J.

Subjects
Colorectal cancer -- Genetic aspects, Colorectal cancer -- Demographic aspects, Colorectal cancer -- Risk factors
Abstract

The significance of genetic factors and mechanisms and their role in the development of colorectal cancer is now increasingly becoming apparent. Population genetics studies have indicated that inherited susceptibility factors may be significant elements in the development of colorectal lesions. Inherited syndromes of colorectal cancer have been identified and include familial adenomatous polyposis, Gardner syndrome, Peutz-Jeghers syndrome, familial juvenile polyposis, and hereditary nonpolyposis colorectal cancer. The chromosomal location of the mutation for familial polyposis has been determined. Other chromosomal locations of DNA sequence deletions have been identified in random cancerous tissues on chromosomes 5, 17, and 18. Population genetic studies, including genealogical data-base studies, pedigree studies, genetic environmental interactions, and molecular genetic studies, have shown that first degree relatives of persons with colon cancer have an increased risk for colorectal cancer. Studies at the molecular level have begun to clarify the genetic mechanisms involved in colon cancer. Screening is recommended for close relatives of colon cancer patients and persons with any of the polyposis syndromes. Specific guidelines and recommendations are detailed for each of the high risk situations and for the family members who are at risk. New and specific recommendations for future research are made, and an extensive bibliography is included. (Consumer Summary produced by Reliance Medical Information, Inc.), Risk and surveillance of individuals with heritable factors for colorectal cancer Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and [...]

Published
1990

9. Diagnosing Lynch syndrome: is the answer in the mouth? Alterations in vascular patterns in the buccal/subgingival mucosa may provide the basis for a non-invasive inexpensive test for recognising hereditary non-polyposis colorectal cancer

Author

Roy, H.K. and Lynch, H.T.

Subjects
Gene mutations -- Physiological aspects -- Research -- Analysis -- Health aspects -- Genetic aspects, Familial diseases -- Health aspects -- Diagnosis -- Care and treatment -- Genetic aspects -- Research, Colorectal diseases -- Research -- Causes of -- Health aspects -- Care and treatment -- Diagnosis -- Genetic aspects, Medical tests -- Analysis -- Physiological aspects -- Health aspects -- Research, Colon cancer -- Health aspects -- Diagnosis -- Genetic aspects -- Causes of -- Care and treatment -- Research, Risk factors (Health) -- Analysis -- Research -- Health aspects -- Physiological aspects, Cancer patients -- Health aspects -- Care and treatment -- Genetic aspects, Colorectal cancer -- Genetic aspects -- Health aspects -- Diagnosis -- Care and treatment -- Research, Gastrointestinal diseases -- Research -- Causes of -- Health aspects -- Care and treatment -- Diagnosis -- Genetic aspects, Phenotype -- Genetic aspects -- Physiological aspects -- Research -- Health aspects -- Analysis, Health, Diagnosis, Care and treatment, Physiological aspects, Analysis, Genetic aspects, Research, Health aspects, Causes of
Abstract

Risk stratification is essential for designing efficacious and cost effective colon cancer screening programmes. One of the most important risk factors for colorectal cancers (CRC) is an inherited predisposition, implicated [...]

Published
2003

11. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial

Author

Burn, J., Gerdes, A.M., Macrae, F., Mecklin, J.P., Moeslein, G., Olschwang, S., Eccles, D., Evans, D.G., Maher, E.R., Bertario, L., Bisgaard, M.L., Dunlop, M.G., Ho, J.W.C., Hodgson, S.V., Lindblom, A., Lubinski, J., Morrison, P.J., Murday, V., Ramesar, R., Side, L., Scott, R.J., Thomas, H.J.W., Vasen, H.F., Barker, G., Crawford, G., Elliott, F., Movahedi, M., Pylvanainen, K., Wijnen, J.T., Fodde, R., Lynch, H.T., Mathers, J.C., Bishop, D.T., CAPP2 Investigators, and Pathology

Subjects
Adenoma, Heterozygote, medicine.medical_specialty, Colorectal cancer, Placebo, Chemoprevention, law.invention, Double-Blind Method, Randomized controlled trial, SDG 3 - Good Health and Well-being, law, Internal medicine, Adenoma - prevention and control, Dietary Carbohydrates, medicine, Humans, media_common.cataloged_instance, European union, media_common, Aspirin, Intention-to-treat analysis, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Cancer, Starch, General Medicine, Anti-Inflammatory Agents, Non-Steroidal - therapeutic use, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Lynch syndrome, Surgery, Colorectal Neoplasms, Hereditary Nonpolyposis - genetics - prevention and control, Aspirin - therapeutic use, business, medicine.drug
Abstract

BACKGROUND: Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. METHODS: In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. RESULTS: 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55.7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0.63 (95% CI 0.35-1.13, p=0.12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0.56 (95% CI 0.32-0.99, p=0.05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0.41 (0.19-0.86, p=0.02) and an IRR of 0.37 (0.18-0.78, p=0.008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. INTERPRETATION: 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55.7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. FUNDING: European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma., link_to_OA_fulltext

Published
2011

12. Results of a Stool BAT-26 Assay in People With HNPCC

Author

Laken, S.J., Lynch, H.T., Urbanowski, J.C., Deters, C., Shuber, A.P., and Watson, P.

Subjects
Human genetics -- Research, Colorectal cancer -- Genetic aspects, Colonoscopy -- Research, Biological sciences
Published
2001

14. Polymorphisms in BRCA1 and 17[Beta]-hydroxysteroid dehydrogenase 2 (EDH17B2) genes as modifiers of ovarian cancer risk in carriers of BRCA1 germline mutations

Author

Sinilnikova, O.M., Ginolhac, S., Gad, S., Bressac-de-Paillerets, B., Chompret, A., Bignon, Y-J., Peyrat, J-P., Fournier, J., Lasset, C., Muller, D., Fricker, J-P., Hardouin, A., Berthet, P., Longy, M., Nogues, C., Lidereau, R., Maugard, C.M., Olschwang, S., Toulas, C., Guimbaud, R., Lynch, H.T., Corbex, M., Goldgar, D., Lenoir, G.M., and Stoppa-Lyonnet, D.

Subjects
Human genetics -- Research, Ovarian cancer -- Genetic aspects, Breast cancer -- Genetic aspects, Genetic disorders -- Research, Biological sciences
Published
2001

18. Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author

Couch, F.J., Gaudet, M.M., Antoniou, A.C., Ramus, S.J., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X.Q., Wang, X.S., Kirchhoff, T., McGuffog, L., Barrowdale, D., Lee, A., Healey, S., Sinilnikova, O.M., Andrulis, I.L., Ozcelik, H., Mulligan, A.M., Thomassen, M., Gerdes, A.M., Jensen, U.B., Skytte, A.B., Kruse, T.A., Caligo, M.A., Wachenfeldt, A. von, Barbany-Bustinza, G., Loman, N., Soller, M., Ehrencrona, H., Karlsson, P., Nathanson, K.L., Rebbeck, T.R., Domchek, S.M., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowocka, E., Huzarski, T., Byrski, T., Gronwald, J., Cybulski, C., Gorski, B., Osorio, A., Duran, M., Tejada, M.I., Benitez, J., Hamann, U., Hogervorst, F.B.L., Os, T.A. van, Leeuwen, F.E. van, Meijers-Heijboer, H.E.J., Wijnen, J., Blok, M.J., Kets, M., Hooning, M.J., Oldenburg, R.A., Ausems, M.G.E.M., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Jacobs, C., Eeles, R.A., Adlard, J., Davidson, R., Eccles, D.M., Cole, T., Cook, J., Paterson, J., Brewer, C., Douglas, F., Hodgson, S.V., Morrison, P.J., Walker, L., Porteous, M.E., Kennedy, M.J., Side, L.E., Bove, B., Godwin, A.K., Stoppa-Lyonnet, D., Fassy-Colcombet, M., Castera, L., Cornelis, F., Mazoyer, S., Leone, M., Boutry-Kryza, N., Bressac-de Paillerets, B., Caron, O., Pujol, P., Coupier, I., Delnatte, C., Akloul, L., Lynch, H.T., Snyder, C.L., Buys, S.S., Daly, M.B., Terry, M., Chung, W.K., John, E.M., Miron, A., Southey, M.C., Hopper, J.L., Goldgar, D.E., Singer, C.F., Rappaport, C., Tea, M.K.M., Fink-Retter, A., Hansen, T.V.O., Nielsen, F.C., Arason, A., Vijai, J., Shah, S., Sarrel, K., Robson, M.E., Piedmonte, M., Phillips, K., Basil, J., Rubinstein, W.S., Boggess, J., Wakeley, K., Ewart-Toland, A., Montagna, M., Agata, S., Imyanitov, E.N., Isaacs, C., Janavicius, R., Lazaro, C., Blanco, I., Feliubadalo, L., Brunet, J., Gayther, S.A., Pharoah, P.P.D., Odunsi, K.O., Karlan, B.Y., Walsh, C.S., Olah, E., Teo, S.H., Ganz, P.A., Beattie, M.S., Rensburg, E.J. van, Dorfling, C.M., Diez, O., Kwong, A., Schmutzler, R.K., Wappenschmidt, B., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Heidemann, S., Niederacher, D., Preisler-Adams, S., Gadzicki, D., Varon-Mateeva, R., Deissler, H., Gehrig, A., Sutter, C., Kast, K., Fiebig, B., Heinritz, W., Caldes, T., Hoya, M. de la, Muranen, T.A., Nevanlinna, H., Tischkowitz, M., Spurdle, A.B., Neuhausen, S.L., Ding, Y.C., Lindor, N.M., Fredericksen, Z., Pankratz, V.S., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Barile, M., Bernard, L., Viel, A., Giannini, G., Varesco, L., Radice, P., Greene, M.H., Mai, P.L., Easton, D.F., Chenevix-Trench, G., Offit, K., Simard, J., OCGN, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators, kConFab Investigators, Consortium Investigators Modifiers, European Commission, National Institutes of Health (US), Breast Cancer Research Foundation, Cancer Research UK, Columbia University, Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, Ministerio de Ciencia e Innovación (España), National Institute for Health Research (UK), University of Helsinki, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministero dell'Istruzione, dell'Università e della Ricerca, Ministero della Salute, National Health and Medical Research Council (Australia), Instituto Nacional del Cáncer (España), National Cancer Institute (US), Avon Foundation for Women, VU University medical center, Human genetics, CCA - Oncogenesis, Clinical Genetics, Pediatric Surgery, Neurology, Medical Oncology, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human Genetics, CCA -Cancer Center Amsterdam, and ARD - Amsterdam Reproduction and Development

Subjects
Oncology, endocrine system diseases, Epidemiology, Estrogen receptor, Breast Neoplasms - epidemiology - genetics - metabolism, DCN PAC - Perception action and control, Immunoenzyme Techniques, 0302 clinical medicine, Risk Factors, Genotype, skin and connective tissue diseases, Ovarian Neoplasms, 0303 health sciences, Ovarian Neoplasms - epidemiology - genetics - metabolism, BRCA1 Protein, Middle Aged, BRCA2 Protein, Prognosis, 3. Good health, DNA-Binding Proteins, Receptors, Estrogen, Risk factors for breast cancer, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Female, Adult, medicine.medical_specialty, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Breast Neoplasms, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Translational research [ONCOL 3], Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Genetics and epigenetic pathways of disease Translational research [NCMLS 6], 030304 developmental biology, Aged, Chromosomes, Human, Pair 19 - genetics, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Cancer, BRCA1 Protein - genetics, medicine.disease, United States, BRCA2 Protein - genetics, Immunology, Mutation, Ovarian cancer, business, Chromosomes, Human, Pair 19, Genome-Wide Association Study, Transcription Factors
Abstract

PMCID: PMC3319317.-- et al., [Background]: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). [Methods]: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. [Results]: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10(-3)). [Conclusions]: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. [Impact]: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers., This research was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. This work was also supported by Cancer Research UK (CR-UK) grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). Support was also provided by the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program and by the Canadian Breast Cancer Research Alliance-grant #019511., A.C. Antoniou is a CR-UK Senior Cancer Research Fellow. D.F. Easton is CR-UK Principal Research Fellow. G. Chenevix-Trench6 is a NHMRC Senior Principal Research Fellow. BFBOCC was supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius. BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to E.J. van Rensburg. BCFR was supported by the National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center; U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). CBCS was supported by The Neye Foundation. CNIO was partially supported by Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, the Spanish Ministry of Science and Innovation (FIS PI08 1120), and the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. CONSIT TEAM was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 “Alleanza contro il Cancro” to L. Varesco and P. Radice, and “Progetto Tumori Femminili” to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to P. Radice), Fondazione Italiana per la Ricerca sul Cancro (Special Project “Hereditary tumors” to P. Radice), Associazione Italiana per la Ricerca sul Cancro (4017 to P. Pujol), and by funds from Italian citizens who allocated the 5 × 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”)., The DKFZ study was supported by funds from the DKFZ. EMBRACE was supported by CR-UK Grants C1287/A10118 and C1287/A11990. D.G. Evans and Fiona Lalloo were supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R.A. Eeles, Elizabeth Bancroft, and Lucia D'Mello were supported by CR-UK Grant C5047/A8385. GC-HBOC was supported by a grant of the German Cancer Aid (grant 109076) and by the Centre of Molecular Medicine Cologne (CMMC). The GEMO study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association “Le cancer du sein, parlons-en!” Award. The Georgetown study was supported by the Familial Cancer Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure. GOG was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program—COPTRG) NCI programs. K. Phillips is the Cancer Council Victoria, Colebatch Clinical Research Fellow. HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. HUNBOCS was supported by the Hungarian Research Grant KTIA-OTKA CK-80745. ICO was supported by Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. IHCC was supported by a Polish Foundation of Science award to K. Jaworska, a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. ILUH was supported by the Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund., INHERIT was supported with J. Simard, Chairholder of the Canada Research Chair in Oncogenetics. IOVHBOCS was supported by Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR), and “Ministero della Salute” (“Progetto Tumori Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9”). kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by the NHMRC [145684, 288704, 454508]. A.-B. Skytte is supported by a NHMRC Senior Research Fellowship. A.K. Godwin was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. The McGill study was supported by the Jewish General Hospital Weekend to End Breast Cancer. M. Thomassen holds a Fonds de la Recherche en Santé du Québec clinician-scientist award. The MSKCC study was supported by the Starr Cancer Consortium, the Breast Cancer Research Foundation, the Norman and Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus Clinical Cancer Research Initiative, the Lymphoma Foundation, and the Sabin Family Research Initiative. The NCI study was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. NNPIO was supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) and the Federal Agency for Science and Innovations (contract 16.512.11.2237)., OCGN was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. OSU-CCG was supported by the Ohio State University Comprehensive Cancer Center. PBCS was supported by an Instituto Toscano Tumori grant to M.A. Caligo. SEABASS was supported by CARIF and University Malaya. The UCSF study was supported by the Helen Diller Family Comprehensive Cancer Center at UCSF, the Avon Foundation, and the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS), NIH/NCI P01 CA130818-02A1. UKFOCR was supported by a project grant from CRUK to P.P.D. Pharoah. The UPENN study was supported Komen Foundation for the Cure to S.M. Domchek, the Breast Cancer Research Foundation to K.L. Nathanson, and NIH grants R01-CA083855 and R01-CA102776 to T.R. Rebbeck. WCRI was supported by the American Cancer Society Clinical Research Professorship #SIOP-06-258-06-COUN.

Published
2012

20. Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Author

Antoniou, A.C., Beesley, J., McGuffog, L., Sinilnikova, O.M., Healey, S., Neuhausen, S.L., Ding, Y.C., Rebbeck, T.R., Weitzel, J.N., Lynch, H.T., Isaacs, C., Ganz, P.A., Tomlinson, G., Olopade, O.I., Couch, F.J., Wang, X.S., Lindor, N.M., Pankratz, V.S., Radice, P., Manoukian, S., Peissel, B., Zaffaroni, D., Barile, M., Viel, A., Allavena, A., Dall'Olio, V., Peterlongo, P., Szabo, C.I., Zikan, M., Claes, K., Poppe, B., Foretova, L., Mai, P.L., Greene, M.H., Rennert, G., Lejbkowicz, F., Glendon, G., Ozcelik, H., Andrulis, I.L., Thomassen, M., Gerdes, A.M., Sunde, L., Cruger, D., Jensen, U.B., Caligo, M., Friedman, E., Kaufman, B., Laitman, Y., Milgrom, R., Dubrovsky, M., Cohen, S., Borg, A., Jernstrom, H., Lindblom, A., Rantala, J., Stenmark-Askmalm, M., Melin, B., Nathanson, K., Domchek, S., Jakubowska, A., Lubinski, J., Huzarski, T., Osorio, A., Lasa, A., Duran, M., Tejada, M.I., Godino, J., Benitez, J., Hamann, U., Kriege, M., Hoogerbrugge, N., Luijt, R.B. van der, Asperen, C.J. van, Devilee, P., Meijers-Heijboer, E.J., Blok, M.J., Aalfs, C.M., Hogervorst, F., Rookus, M., Cook, M., Oliver, C., Frost, D., Conroy, D., Evans, D.G., Lalloo, F., Pichert, G., Davidson, R., Cole, T., Cook, J., Paterson, J., Hodgson, S., Morrison, P.J., Porteous, M.E., Walker, L., Kennedy, M.J., Dorkins, H., Peock, S., Godwin, A.K., Stoppa-Lyonnet, D., Pauw, A. de, Mazoyer, S., Bonadona, V., Lasset, C., Dreyfus, H., Leroux, D., Hardouin, A., Berthet, P., Faivre, L., Loustalot, C., Noguchi, T., Sobol, H., Rouleau, E., Nogues, C., Frenay, M., Venat-Bouvet, L., Hopper, J.L., Daly, M.B., Terry, M.B., John, E.M., Buys, S.S., Yassin, Y., Miron, A., Goldgar, D., Singer, C.F., Dressler, A.C., Gschwantler-Kaulich, D., Pfeiler, G., Hansen, T.V.O., Jnson, L., Agnarsson, B.A., Kirchhoff, T., Offit, K., Devlin, V., Dutra-Clarke, A., Piedmonte, M., Rodriguez, G.C., Wakeley, K., Boggess, J.F., Basil, J., Schwartz, P.E., Blank, S.V., Toland, A.E., Montagna, M., Casella, C., Imyanitov, E., Tihomirova, L., Blanco, I., Lazaro, C., Ramus, S.J., Sucheston, L., Karlan, B.Y., Gross, J., Schmutzler, R., Wappenschmidt, B., Engel, C., Meindl, A., Lochmann, M., Arnold, N., Heidemann, S., Varon-Mateeva, R., Niederacher, D., Sutter, C., Deissler, H., Gadzicki, D., Preisler-Adams, S., Kast, K., Schonbuchner, I., Caldes, T., Hoya, M. de la, Aittomaki, K., Nevanlinna, H., Simard, J., Spurdle, A.B., Holland, H., Chen, X.Q., Platte, R., Chenevix-Trench, G., Easton, D.F., Ontario Canc Genetics Network, SWE-BRCA, HEBON, EMBRACE, GEMO, Breast Canc Family Registry, kConFab, CIMBA, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human genetics, CCA - Oncogenesis, Human Genetics, Pathology, Clinical Genetics, Pediatric Surgery, Medical Oncology, and Internal Medicine

Subjects
Oncology, Cancer Research, endocrine system diseases, Vesicular Transport Proteins, Gene mutation, 0302 clinical medicine, Risk Factors, Genotype, skin and connective tissue diseases, Aged, 80 and over, 0303 health sciences, BRCA1 Protein, High Mobility Group Proteins, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Female, Breast disease, Receptors, Progesterone, Adult, Heterozygote, medicine.medical_specialty, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Alleles, Aged, 030304 developmental biology, BRCA2 Protein, Hereditary cancer and cancer-related syndromes [ONCOL 1], Sodium-Bicarbonate Symporters, Haplotype, Cancer, genome-wide association estrogen-receptor loci variants, medicine.disease, Survival Analysis, TOX3, Mutation, Trans-Activators, Cancer research, Apoptosis Regulatory Proteins
Abstract

The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03–1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01–1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10−11 − 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers. Cancer Res; 70(23); 9742–54. ©2010 AACR.

Published
2010

21. C Modifies Breast Cancer Risk among BRCA2 Mutation Carriers: Results from a Combined Analysis of 19 Studies

Author

Antoniou, A.C., Sinilnikova, O.M., Simard, J., Leone, M., Dumont, M., Neuhausen, S.L., Struewing, J.P., Stoppa-Lyonnet, Dominique, Barjhoux, L., Hughes, D.J., Coupier, I., Belotti, M., Lasset, Christine, Bonadona, Valérie, Bignon, Y.J., Rebbeck, T.R., Wagner, T., Lynch, H.T., Domchek, S.M., Nathanson, K.L., Garber, J.E., Weitzel, J., Narod, S.A., Tomlinson, G., Olopade, O.I., Godwin, A., Isaacs, C., Jakubowska, A., Lubinski, J., Gronwald, J., Gorski, B., Byrski, T., Huzarski, T., Peock, S., Cook, M., Baynes, C., Murray, A., Rogers, M., Daly, P.A., Dorkins, H., Schmutzler, R.K., Versmold, B., Engel, C., Meindl, A., Arnold, N., Niederacher, D., Deissler, H., Spurdle, A.B., Chen, X., Waddell, N., Cloonan, N., Kirchhoff, T., Offit, K., Friedman, E., Kaufmann, B., Laitman, Y., Galore, G., Rennert, G., Lejbkowicz, F., Raskin, L., Andrulis, I.L., Ilyushik, E., Ozcelik, H., Devilee, P., Vreeswijk, M.P., Greene, M.H., Prindiville, S.A., Osorio, A., Benitez, J., Zikan, M., Szabo, C.I., Kilpivaara, O., Nevanlinna, H., Hamann, U., Durocher, F., Arason, A., Couch, F.J., Easton, D.F., Chenevix-Trench, G., Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]
Published
2007

23. Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene

Author

Hughes, D.J., Ginolhac, S.M., Coupier, I., Barjhoux, L., Gaborieau, V., Bressac-De-Paillerets, B., Chompret, A., Bignon, Y.J., Uhrhammer, N., Lasset, Christine, Giraud, S., Sobol, H., Hardouin, A., Berthet, P., Peyrat, J.P., Fournier, J., Nogues, C., Lidereau, R., Muller, D., Fricker, J.P., Longy, M., Toulas, C., Guimbaud, R., Yannoukakos, D., Mazoyer, S., Lynch, H.T., Lenoir, G.M., Goldgar, D.E., Stoppa-Lyonnet, Dominique, Sinilnikova, O.M., Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]
Published
2005

29. Prévention du cancer colorectal: mise à jour des directives

Author

Winawer, S.J., John, D.J. St., Bond, J.H., Rozen, P., Burt, R.W., Waye, J.D., Kronborg, O., O'Brien, M.J., Bishop, D.T., Kurtz, R.C., Shike, M., Swaroop, S.V., Levin, B., Fruhmorgen, P., and Lynch, H.T.

Subjects
Update
Published
1995

31. Communication and technology in genetic counseling for familial cancer.

Author

Lynch, H.T., Snyder, C., Stacey, M., Olson, B., Peterson, S.K., Buxbaum, S., Shaw, T., and Lynch, P.M.

Subjects
*GENETIC counseling, *GERM cells, *COMMUNICATION & technology, *CANCER patients, *FAMILIAL diseases
Abstract

When a cancer predisposing germline mutation is detected in an index case, the presence of the underlying syndrome is confirmed and the potential for predictive testing of at-risk relatives is established. However, the reporting of a positive family history does not routinely lead to communication of information about risk to close, much less distant relatives. This review summarizes information technology utilized to address penetration or 'reach' of knowledge of risk within extended families, including the use of telephone and video counseling to reach distant patients, and anticipate novel internet-based processes for communication between investigators and relatives. [ABSTRACT FROM AUTHOR]

Published
2014
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34. Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families

Author

Tonin, P., primary, Weber, B., additional, Offit, K., additional, Couch, F., additional, Rebbeck, T.R., additional, Neuhausen, S., additional, Godwin, A.K., additional, Daly, M., additional, Wagner-Costalos, J., additional, Berman, D., additional, Grana, G., additional, Fox, E., additional, Kane, M.F., additional, Kolodner, R.D., additional, Krainer, M., additional, Haber, D.A., additional, Struewing, J.P., additional, Warner, E., additional, Rosen, B., additional, Lerman, C., additional, Peshkin, B., additional, Norton, L., additional, Serova, O., additional, Foulkes, W.D., additional, Lynch, H.T., additional, Lenoir, G.M., additional, Narod, S.A., additional, and Garber, J.E., additional

Published
1996
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36. A P1-based physical map of the region from D17S776 to D17S78 containing the breast cancer susceptibility gene BRCA1

Author

Neuhausen, S.L., primary, Swensen, J., additional, Miki, Y., additional, Llu, Q., additional, Tavtiglan, S., additional, Shattuck-Eidens, D., additional, Kamb, A., additional, Hobbs, M.R., additional, Gingrich, J., additional, Shizuya, H., additional, Kim, U.-J., additional, Cochran, C., additional, Futreal, P.A., additional, Wiseman, R.W., additional, Lynch, H.T., additional, Tonin, P., additional, Narod, S., additional, Cannon-Albright, L., additional, Skolnick, M.H., additional, and Goldgar, D.E., additional

Published
1994
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41. Carrier risk status changes resulting from mutation testing in hereditary non-polyposis colorectal cancer and hereditary breast-ovarian cancer.

Author

Watson, P., Narod, S.A., Fodde, R., Wagner, A., Lynch, J.F., Tinley, S.T., Snyder, C.L., Coronel, S.A., Riley, B., Kinarsky, Y., and Lynch, H.T.

Subjects
BREAST cancer, OVARIAN cancer, COLON cancer
Abstract

Describes the change in the distribution of carrier risk status resulting from testing in hereditary breast-ovarian cancer and hereditary non-polyposis colorectal cancer families. Most common type of carrier risk change; Change from carrier risk status from uncertainty to certainty accounting for 89 percent of risk changes resulting from testing.

Published
2003
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47. Familial gastric cancer: overview and guidelines for management

Author

Yokota, J., Vogelsang, H., Wiesner, G.L., Keller, G., Powell, S.M., Park, K.G.M., Lewis, F.R., Wight, D., Jackson, C.E., Roviello, F., Huntsman, D.G., Jankowski, J.A., Richards, F.M., Maher, E.R., MacLeod, P., Caldas, C., Pharoah, P.D.P., Gayther, S.A., Oliveira, C., Grehan, N., Ponder, B.A.J., Carneiro, F., Seruca, R., and Lynch, H.T.

Abstract

Families with autosomal dominant inherited predisposition to gastric cancer have been described. More recently, germline E-cadherin/CDH1 mutations have been identified in hereditary diffuse gastric cancer kindred. The need to have protocols to manage and counsel these families in the clinic led a group of geneticists, gastroenterologists, surgeons, oncologists, pathologists, and molecular biologists to convene a workshop to produce consensus statements and guidelines for familial gastric cancer. Review of the available cancer pathology from people belonging to families with documented germline E-cadherin/CDH1 mutations confirmed that the gastric cancers were all of the diffuse type. Criteria to define the different types of familial gastric cancer syndromes were agreed. Foremost among these criteria was that review of histopathology should be part of the evaluation of any family with aggregation of gastric cancer cases. Guidelines for genetic testing and counselling in hereditary diffuse gastric cancer were produced. Finally, a proposed strategy for clinical management in families with high penetrance autosomal dominant predisposition to gastric cancer was defined.

Published
1999

48. Genetic susceptibility to non-polyposis colorectal cancer

Author

Lynch, H.T. and Chapelle, A. de la

Abstract

Familial colorectal cancer (CRC) is a major public health problem by virtue of its relatively high frequency. Some 15-20% of all CRCs are familial. Among these, familial adenomatous polyposis (FAP), caused by germline mutations in the APC gene, accounts for less than 1%. Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, accounts for approximately 5-8% of all CRC patients. Among these, some 3% are mutation positive, that is, caused by germline mutations in the DNA mismatch repair genes that have so far been implicated (MLH1, MSH2, MSH6, PMS1, and PMS2). Most of the remaining patients belonging to HNPCC or HNPCC-like families are still molecularly unexplained. Among the remaining familial CRCs, a large proportion is probably caused by gene mutations and polymorphisms of low penetrance, of which the I1307K polymorphism in the APC gene is a prime example.Molecular genetic findings have enabled hereditary CRC to be divided into two groups: (1) tumours that show microsatellite instability (MSI), occur more frequently in the right colon, have diploid DNA, harbour characteristic mutations such as transforming growth factor β type II receptor and BAX, and behave indolently, of which HNPCC is an example; and (2) tumours with chromosomal instability (CIN), which tend to be left sided, show aneuploid DNA, harbour characteristic mutations such as K-ras, APC, and p53, and behave aggressively, of which FAP is an example.This review focuses most heavily on the clinical features, pathology, molecular genetics, surveillance, and management including prophylactic surgery in HNPCC. Because of the difficulty in diagnosing HNPCC, a detailed differential diagnosis of the several hereditary CRC variants is provided. The extant genetic and phenotypic heterogeneity in CRC leads to the conclusion that it is no longer appropriate to discuss the genetics of CRC without defining the specific hereditary CRC syndrome of concern. Therefore, it is important to ascertain cancer of all anatomical sites, as well as non-cancer phenotypic stigmata (such as the perioral and mucosal pigmentations in Peutz-Jeghers syndrome), when taking a family cancer history.

Published
1999

50. Breast cancer genetics: Family history, heterogeneity, molecular genetic diagnosis, and genetic counseling

Author

Lynch, H.T. and Lynch, J.F.

Abstract

Between 5% and 10% of breast cancer cases can be traced to primary genetic factors. Before the discovery of the BRCA1 and BRCA2 genes, if a first-degree relative in direct genetic lineage had hereditary breast cancer or hereditary breast-ovarian cancer syndrome, the best estimate of family members' genetic risk for breast cancer was 50%. Now the lifetime cancer destiny of a patient who carries a BRCA1 or BRCA2 germ line mutation can be determined with an extraordinary degree of precision. However, a major concern facing clinicians is how to use this powerful genetic knowledge without harming the patient. This presentation focuses on the need for (a) compilation of a detailed family history of cancer of all anatomic sites; (b) understanding of the natural history of hereditary breast cancer and its heterogeneous forms and the pathobiology of hereditary breast cancer; and (c) preparation for performance of genetic counseling that is based on the results of DNA sequencing to detect genes related to cancer susceptibility. The discussion addresses the advantages of this molecular genetic movement, which include the abilities (a) to predict who is and who is not at inordinately high risk for cancer; (b) to provide opportunities for highly targeted disease surveillance and management; (c) to give patients the information they need to make appropriate longterm decisions about matters such as procreation; and (d) to give genetic counselors the information they need to appreciate the emotions patients may encounter, such as fear, anxiety, and apprehension, and the ordeal of being subjected to discrimination by insurance companies and employers.

Published
1996
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