Cancer genetics - Breast Cancer genetics prostate

The development of cancer is associated with a fundamental genetic change within the cell. Evidence for the genetic origin of cancer is based on the following:

• Some cancers show a familial predisposition.
• Most known carcinogens act through induced mutations.
• Susceptibility to some carcinogens depends on the ability of cellular enzymes to convert them to a mutagenic form.
• Genetically determined traits associated with a deficiency in the enzymes required for DNA repair are associated with an increased risk of cancer.
• Some cancers are associated with chromosome 'instability' because of deficiencies in mismatch repair genes.
• Many malignant tumours represent clonal proliferations of neoplastic cells.
• Many tumours contain well-described cytogenetic abnormalities, which involve mutated or abnormally regulated oncogenes and tumour suppressor genes with transforming activity in cell lines.

Mutations may occur in the germline and therefore be present in every cell in the body, or they may occur by somatic mutation in response, for example, to carcinogens, and therefore be present only in the cells of the tumour.

Expression of the mutation and hence carcinogenesis will depend upon the penetrance (due to level of expression and presence of other genetic events) of the gene and whether the mutated allele has a dominant or recessive effect. There are a small group of autosomal dominant inherited mutations such as RB (in retinoblastoma) and a small group of recessive mutation. Carriers of the recessive mutations are at risk of developing cancer if the second allele becomes mutated, leading to 'loss of heterozygosity' within the tumour although this is seldom sufficient as carcinogenesis is a multistep process.

Malignant transformation may result from a gain in function as cellular proto-oncogenes become mutated, (e.g. ras ), amplified (e.g. HER2 ), or translocated (e.g. BCR-ABL ). However, these mutations are insufficient to cause malignant transformation by themselves. Alternatively, there may be a loss of function of tumour suppressor genes that normally suppress growth and differentiation. A third mechanism involves alterations in the genes controlling the transcription of the oncogenes or tumour suppressor genes.

Cancer Tip Fruit and vegetable consumption may not significantly reduce breast cancer risk, but fruits and vegetables contain phytochemicals and antioxidants that may be protective against other cancers and heart disease. A minimum of five servings per day is recommended.

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