Epigenetics
The classical view of cancer is a set of diseases driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes, and in chromosomal abnormalities. A role for epigenetic alterations was identified in the early 21st century.Epigenetic alterations are functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation), histone modification and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1). Each of these alterations regulates gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, endure for multiple generations, and can be considered as equivalent to mutations. Epigenetic alterations occur frequently in cancers. As an example, one study listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers and many others were hypermethylated in more than 50% of colon cancers.While epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations may occur early in progression to cancer and are a possible cause of the genetic instability characteristic of cancers.Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the figure at the 4th level from the top.
Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers. Cancer from work-related substance exposures may cause between 2 and 20% of cases, causing at least 200,000 deaths. Cancers such as lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.Exposure to perfluorooctanoic acid (PFOA), which is predominantly used in the production of Teflon, is known to cause two kinds of cancer. Diet and exercise
Diet, physical inactivity and obesity are related to up to 30–35% of cancer deaths. In the United States, excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of cancer deaths. A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country. Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system.