Theories of Cancer: Which Explanation Holds Up Best?

Gene theory proposes that DNA damage leads to cancer. In 1914, Theodor Boveri suggested cancer results from defects in chromosome segregation during cell division. He based his hypothesis on observations in nematodes and sea urchins, not studies of human tumor cells.

Somatic Mutation theory states that gene mutations drive cell proliferation. Knudson linked the Philadelphia (Ph1) chromosome to the chronic myelocytic oncogene. However, Ph1 and ABL oncogene mutations have also been found in individuals without CML or cancer, indicating these findings alone do not cause the disease.

Oncogene theory holds that oncogenes cause cancer. Isocitrate dehydrogenase 1 (IDH1) can act as both an oncogene and a tumor suppressor, complicating this view. Michael Stratton’s research showed that introducing DNA from human cancers into normal NIH3T3 cells transformed them into cancer cells, but only 2 out of 24 cancer samples produced this effect.

Viral theory proposes that viruses cause cancer, accounting for 15% of human cases. Viruses such as RSV, EBV, KSHV, HPV, HBV, HCV, HIV, HCMV, and HTLV-1 can alter mitochondrial function. Viral infections trigger inflammation, which damages oxidative phosphorylation and can impair cellular respiration.

Warburg theory suggests that insufficient cellular respiration is the root cause of cancer. In a study of liver cancer in rats exposed to the carcinogen butter yellow, respiratory activity initially increased for several weeks, then rapidly declined to minimal or no activity.

Insufficient respiration caused by mitochondrial injury is the primary cause of cancer. Viruses, inflammation, and carcinogens damage mitochondria and disrupt respiration. DNA alterations and gene mutations are effects of insufficient respiration, not the initial cause of cancer.

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