Colon cancer genetics / edited by Patrick M. Lynch and Henry T. Lynch.

Date:
[1985]
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Colon cancer genetics / edited by Patrick M. Lynch and Henry T. Lynch. Source: Wellcome Collection.

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    10 COLON CANCER GENETICS Steroid nucleus (nuclear dehydrogenase), and release of toxic products from conjugated compounds (beta-glucuronidase).^^ Reddy and Wynder found concentrations of deoxycholic and lithocholic acid, cholesterol, coprostanol, and cholestan-3-alpha, 5-alpha, 6-alpha-triol in colon cancer patients and patients with adenomatous polyps to be higher than controls.Consequently, 7-alpha-dehydroxylase and cholesterol- dehydrogenase activity were elevated. Further study of endogenous break¬ down products was recommended. GENETIC-ENVIRONMENTAL INTERACTION Reddy found that patients with colon cancer precursors such as familial polyposis coli (FPC), ulcerative colitis, and adenomatous polyps, fall into three distinct groups relevant to fecal-bile-acid and metabolite profiles.^^ Patients with PFC excrete higher amounts of undegraded cholesterol than controls. Those with adenomatous polyps excrete more cholesterol-metabolite bile acids than normal controls. '''' Those with ulcerative colitis yield rela¬ tively greater concentrations of neutral sterols but no excess of bile acids. The central focus—cholesterol metabolites—was therefore believed to be genetic. Genetic control is also apparent in other syndromes characterized by colon cancer (discussed at length in other sections of this book). These include the cancer family syndrome (CPS), Peutz-Jeghers syndrome, and juvenile polyposis coli, all of which follow an autosomal-dominant mode of inheritance and are characterized by multiple primary malignancies and an early age of onset. Chemical carcinogenesis occurs in two stages: initiation and promotion.^^ Knudson's model of malignant transformation in hereditary cancer syn¬ dromes based on a two-stage process presupposes that the two stages of malignant transformation in hereditary cancer are germinal mutation and somatic mutation. In hereditary forms of cancer, a germinal mutation predisposes malignant transformation by a single mutagenic event. Multiple primary malignancies and early age of onset, both characteristics of heredi¬ tary forms of cancer, are easily explained by this model. A germinal mutation may affect all cells in a cell line, resulting in multiple opportunities for primary tumor development. A germinal mutation is present at birth, and the time span required for a single somatic mutation is genetically signifi¬ cantly less than that required for two somatic mutations in patients lacking in inborn traits. Supportive examples of this two-hit hypothesis include xeroderma pigmentosum (XP), retinoblastoma, and adenomatosis of the colon and rectum.
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