Most types of cancer are caused by alterations of regulatory gene elements, steering cell growth, division and differentiation. Only in a few cases, inherited mutations are the reason for oncogenic disorders.

There are three general types of genes that are associated with causing cancer:

• Tumour suppressor genes regulate growth, development, and cell signalling pathways (eg. p53, retinoblastoma gene RB1). Their absence or malfunction can result in development of cancer. Tumour suppressor genes usually appear to be recessive.

• Oncogenes are mutated proto-oncogenes, which promote the specialisation and division of healthy cells (e.g.RAS, HER2/neu). Generally, oncogenes are dominant.

• DNA repair genes are involved in DNA repair and proof-reading of alterations like mismatches. They play a crucial role in maintaining genetic stability (e.g. XRCC1 and 3) Mutations may cause transcription and translation into truncated or malfunctioning RNAs and proteins, respectively.

Most tumours originate from multiple alterations of a cell´s genotype. Vogelstein's model of colon cancer describes a series of mutations detected in both, proto-oncogenes and tumour suppressor genes.

For further information visit the National Cancer Institute (US), the Australian Centre for Genetics Education, the Inova Health System or educational material from Wellesley College (US).

The majority of cancers are associated with somatic mutations. Here, a single or few cells are affected postnatally, triggered by environmental exposures (such as smoking), behaviour (e.g. unbalanced diet), or by chance alone. Mutations in a genome of an organism may accumulate over its life span. If mutations affect cell cycle regulating genes, accelerated self-renewal of stem cells and the circumvention of apoptosis (i.e. programmed cell death) may be the result, and thus oncogenic disorders. Thus, genetic aberrations seem to be the main agents of cancer and tumours, most of them somatic and hence, luckily not inherited. For instance, breast and colon cancer are inherited by less than 10 per cent.

But even if genes or mutations predisposing cancer exist, this cannot explain cancer development alone due to other genetic or environmental factors potentially modifying the risk and reducing the harm of these predispositions.
For example, for persons carrying mutations for either BRCA 1 or BRCA 2, which are thought to correlate with a hereditary predisposition to breast and ovarian cancer, the onset of cancer is not the irrevocable prognosis.

For the establishment of risk models, it seems important to study the mechanisms leading to the clinical manifestation of a predisposition. The numerous methods to estimate the penetrance of different mutations are not without potential inaccuracy. For instance, for women aged 70, the correlation between the penetrance of BRCA1 and BRCA2 and the onset of breast cancer ranges from 14% to 87%. Newly adapted risk models (Gail model) are the basis of the Breast Cancer Risk Assessment Tool of the National Cancer Institute (USA).
For further information click here.





Generally, three types of cancers are distinguished:

1) Cancers that are associated with a mutation in a single, highly-penetrant gene are called hereditary cancers (HCs). Examples include BRCA1, BRCA2, FAP (APC), etc. Thus, in HCs, the mutation contributes for the majority risks. In such cases, environmental factors play only an ancillary role.

2) Familial cancer (FC): Occasionally, one type of cancer occurs familiarly cummutative, but less frequently than HCs would. A likely causation may be a small number of co-inherited factors. Two siblings developing colorectal cancer, with no prior case in the family, might be an example for familial predisposition.

3) Sporadic cancer (SC): SCs are termed those types of cancer, which are particularly triggered by environmental influences. For example, a vast majority of lung cancers are caused by smoking and exhausted fumes.

For further information visit the American Society of Clinical Oncology or the Cancer Research UK.

Also visit the casestudies: breastcancer, obesity, cancer & stress