Genetic predispositions to cancer

The answer is b. (Murray, pp 787-811. Scriver, pp 521-552. Sack, pp 85—96. Wilson, pp 187-224.) Genetic predisposition to cancer is best understood by the Knudsen hypothesis, where two independent mutations or hits are required to produce neoplasia of a somatic tissue. In many hereditary cancers, the first hit is a germ-line mutation that is transmitted in families. Individuals who inherit this mutation are much more likely to... 

Frank, S. A. (2004). Genetic predisposition to cancer—Insights from population genetics. Nat Rev Genet 5, 764-772. 

F. Confrontation of the Model with the Basic Concepts in Genetic Predisposition to Cancer... 

Fig. 6 Cartoon presentation of the basic concepts of genetic predisposition to cancer (see text for explanations).

Colon cancer occurs at a much higher rate in industrialized parts of the world such as North America and Europe, whereas the lowest rates are seen in less-developed areas, suggesting that environmental and dietary factors influence the development of colon cancer.2 In addition to these environmental factors, colon cancers are known to develop more frequently in certain families, and genetic predisposition to this cancer is well known. 

Without regard to therapy, potentially valuable diagnostic tests are available for presymptomatic evaluation of risk of breast cancer due to predisposition from BRCA 1 or BRCA 2 and of colon cancer related to familial adenomatous polyposis (APC gene) or hereditary nonpolyposis mismatch repair genes (MSH 2). Genetic predisposition to Alzheimer disease associated with ApoE4 is neither sufficient nor necessary to lead to the clinical condition, and no definitive therapy is available. 

Although most human cancers are acquired diseases, all types may occur in heritable or nonheritablc forms, and heritabiUty may be associated with a dominant or recessive expression at a single locus, or with a constitutional chromosome anomaly. The changes associated with inherited predisposition to cancer must involve genetic alterations or mutational events at the sites of chromosome anomalies. There is now evidence for this in retinoblastomas. 

I am confident that with the approach of the postgenome era, an ever-increasing number of human genes will be discovered and their functions elucidated. Combined with the knowledge of human gene polymorphism, genotyping will allow prediction of the genetic predisposition to certain diseases, such as cancer. The new millennium will usher us in a new era of disease-predictive medicine. 

Kaisary A, Smith P, Jacqz E, et al. Genetic predisposition to bladder cancer ability to hydroxylate debrisoquine and mephenytoin as risk factors. Cancer Res 1987 47 5488-5493. 

Shibata, A., and Whittemore, A. S., Genetic predisposition to prostate cancer possible explainations for ethnic differences in risk. Prostate 32,65-72 (1997). 

Table 7 Examples of genetic development in humans predisposition to cancer...

It s not about genetic predispositions to certain illnesses or conditions. Once you know this one vital secret, you will hold the power to create—and maintain—your own good health. Imagine equipping your body with the tools it needs to ward off cold and flu viruses, heart disease, arthritis, osteoporosis, diabetes, kidney disease, and cancer. And as a bonus, you ll have more energy and feel better than ever, and excess weight will simply melt off ... 

Burke W, Peterson G, Lynch P, Botkin J, Daly M, Garber J, et al. Recommendations for follow-up care of individuals with inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium. JAMA 1997 277 915-9. 

Still other substances may accelerate or promote the glycolytic reactions, some of which may be related to genetic causes. For instance, there may be a genetic predisposition to promote the activity of the enzyme or enzymes involved in cancer cell metabolism. 

Lyn D, Chemey BW, Lalande M et al. A duplicated r on is responsible for the polyfADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer. Am J Hum Genet 1993 52fl) 124-134. 

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