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The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis. DNA damage is considered to be the primary cause of cancer. [17] More than 60,000 new naturally-occurring instances of DNA damage arise, on average, per human cell, per day, due to endogenous cellular processes (see article DNA damage (naturally occurring)).
Certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer. [3] Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of colon cancer cases. [13]
Ulceration can cause bleeding that can lead to symptoms such as coughing up blood (lung cancer), anemia or rectal bleeding (colon cancer), blood in the urine (bladder cancer), or abnormal vaginal bleeding (endometrial or cervical cancer). Although localized pain may occur in advanced cancer, the initial tumor is usually painless.
High-normal levels of the bile acid deoxycholic acid cause apoptosis in human colon cells, [56] but may also lead to colon cancer if repair and apoptotic defenses are insufficient. [57] Apoptosis serves as a safeguard mechanism against tumorigenesis. [58] It prevents the increased mutagenesis that excess DNA damage could cause, upon replication ...
The accumulation of certain mutations over generations of somatic cells is part of cause of malignant transformation, from normal cell to cancer cell. [ 113 ] Cells with heterozygous loss-of-function mutations (one good copy of gene and one mutated copy) may function normally with the unmutated copy until the good copy has been spontaneously ...
In fact, a series of several mutations to certain classes of genes is usually required before a normal cell will transform into a cancer cell. [ 19 ] Damage to DNA can be caused by exposure to radiation, chemicals, and other environmental sources, but mutations also accumulate naturally over time through uncorrected errors in DNA transcription ...
A metabolite of benzopyrene forms an intercalated DNA adduct, at center. In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could lead to the development of cancerous cells, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers of exposure.
When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates strongly increase in cells defective in DNA mismatch repair [36] [37] or in homologous recombinational repair (HRR). [38]