Cell transformation

Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor.

There are many causes of primary malignant transformation, or tumorigenesis. Most human cancers in the United States are caused by external factors, and these factors are largely avoidable. These factors were summarized by Doll and Peto in 1981, and were still considered to be valid in 2015. These factors are listed in the table.

^a Reproductive and sexual behaviors include: number of partners; age at first menstruation; zero versus one or more live births

Colon cancer provides one example of the mechanisms by which diet, the top factor listed in the table, is an external factor in cancer. The Western diet of African Americans in the United States is associated with a yearly colon cancer rate of 65 per 100,000 individuals, while the high fiber/low fat diet of rural Native Africans in South Africa is associated with a yearly colon cancer rate of <5 per 100,000. Feeding the Western diet for two weeks to Native Africans increased their secondary bile acids, including carcinogenic deoxycholic acid, by 400%, and also changed the colonic microbiota. Evidence reviewed by Sun and Kato indicates that differences in human colonic microbiota play an important role in the progression of colon cancer.

A second example, relating a dietary component to a cancer, is illustrated by lung cancer. Two large population-based studies were performed, one in Italy and one in the United States. In Italy, a study population of 1721 individuals diagnosed with lung cancer and no severe disease and 1918 control individuals with absence of lung cancer history or any advanced diseases. All individuals filled out a food frequency questionnaire including consumption of walnuts, hazelnuts, almonds, and peanuts, and indicating smoking status. In the United States, 495,785 members of AARP were questioned on consumption of peanuts, walnuts, seeds, or other nuts in addition to other foods and smoking status. In this U.S. study 18,533 incident lung cancer cases were identified during up to 16 years of follow-up. Overall, individuals in the highest quintile of frequency of nut consumption had a 26% lower risk of lung cancer in the Italian study and a 14% lower risk of lung cancer in the U.S. study. Similar results were obtained among individuals who were smokers.

The most important chemical compounds in smoked tobacco that are carcinogenic are those that produce DNA damage since such damage appears to be the primary underlying cause of cancer. Cunningham et al. combined the microgram weight of the compound in the smoke of one cigarette with the known genotoxic effect per microgram to identify the most carcinogenic compounds in cigarette smoke. These compounds and their genotoxic effects are listed in the article Cigarette. The top three compounds are acrolein, formaldehyde and acrylonitrile, all known carcinogens.

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