CISN - Cancer Research - What Causes Cancer? pg.3

What Causes Cancer? - Page 3

Cancer Involves Multiple Mutations

A sound body depends on the continuous interplay of thousands of proteins, acting together in just the right amounts and in just the right places. Each properly functioning protein is the product of an intact gene.

Many, if not most, diseases have their roots in our genes. Common disorders such as heart disease and most cancers arise from a complex interplay among multiple genes and between genes and factors in the environment. Cancer may begin because of the accumulation of multiple mutations.

CISN Summary:

1. Cancer-associated mutations, whether somatic or germ line, whether point mutations or large deletions, alter key proteins and their functions in the human biosystem.

2. A wide variety of mutations seem to be involved.

3. Even mutations in noncoding regions, such as in promoters, enhancers, or negative regulatory regions, can result in under or over expression of proteins needed for normalcy.

4. Other mutations may cause production of important checkpoint proteins to malfunction.

5. Collectively, these mutations conspire to change a genome from normal to cancerous.

6. It is important to note that genes themselves do not cause disease. Genetic disorders are caused by mutations that make a gene function improperly.

7. Some mutations alter a gene's DNA base sequence but do not change the function of the protein made by the gene. These mutations were often called silent mutations and were thought to be harmless. New research may prove this theory wrong.

8. Enzymes often repair Gene mutations that could cause cancer, before the gene is expressed (makes a protein) and there is no problem.

Epigenetics: More about this in Advances in Cancer Research

Early in cancer research, it was thought that all cancers began as mutations caused by mistakes in the cell cycle, replication, oncogenes or tumor suppressor genes. Researchers now know that cancer can occur with no mutations to the DNA.

Epigenetics refers to changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence (hence the name epi - "in addition to" - genetics).

Epigenetic factors are mechanisms outside the gene that can cause changes, such as a cell's exposure to carcinogens or hormones, or genetic variations that modify a gene or its protein by adding or subtracting chemical groups such as a methyl group known as methylation. Methylation of the genome can render areas silent.

Methylation adds methyl groups to newly synthesized strands of DNA. This activity makes sure that daughter molecules of DNA maintain a methylation pattern after cell division.

For example: Hormone and reproductive factors may influence certain cancer-linked mutations. Breast and ovarian cancer are more likely to occur in women with early menarche, late menopause, and a first child after age 30 (or no children at all). These factors are believed to be linked to a woman's exposure to estrogen and progesterone and their effects on cell differentiation in the breast that occur during pregnancy.

In cancer, both the genotype and the phenotype change over time. Epigenetic factors play a key role in these changes.

CISN Summary

1. There is no change in the underlying DNA sequence of the organism; instead, nongenetic factors cause the organism's genes to behave (or "express themselves") differently.

2. Epigenetic changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.

3. In 2008, the National Institutes of Health announced that $190 million had been earmarked for epigenetic research over the next five years. In announcing the funding, government officials noted that epigenetics has the potential to explain mechanisms of aging, human development, and the origins of cancer, heart disease and mental illness, as well as several other conditions.