This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor.
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.
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.
[11] In 1995 epidemiologic evidence indicated that Helicobacter pylori infection increases the risk for gastric carcinoma.
[12] More recently, experimental evidence showed that infection with Helicobacter pylori cagA-positive bacterial strains results in severe degrees of inflammation and oxidative DNA damage, leading to progression to gastric cancer.
The average number of DNA sequence mutations in the entire genome of breast cancer tissue is about 20,000.
In cancers, loss of gene expression occurs about 10 times more frequently by epigenetic transcription silencing (caused, for example, by promoter hypermethylation of CpG islands) than by mutations.
In mammals, these small non-coding RNA molecules regulate about 60% of the transcriptional activity of protein-encoding genes.
Almost one third of miRNA promoters active in normal mammary cells were found to be hypermethylated in breast cancer cells, and that is a several fold greater proportion of promoters with altered methylation than is usually observed for protein coding genes.
[32] Thus it appears that much of the reduction or absence of BRCA1 in high grade ductal breast cancers may be due to over-expressed miR-182.
Silencing of a DNA repair gene by hypermethylation or other epigenetic alteration appears to be a frequent step in progression to cancer.
Further, the article Werner syndrome ATP-dependent helicase indicates the DNA repair gene WRN has a promoter that is often hypermethylated in a variety of cancers, with WRN hypermethylation occurring in 11% to 38% of colorectal, head and neck, stomach, prostate, breast, thyroid, non-Hodgkin lymphoma, chondrosarcoma and osteosarcoma cancers.
Such silencing likely acts similarly to a germ-line mutation in a DNA repair gene, and predisposes the cell and its descendants to progression to cancer.
Bhattacharjee et al. further reviewed the role of arsenic in causing telomere dysfunction, mitotic arrest, defective apoptosis, as well as altered promoter methylation and miRNA expression.
[42] Nickel compounds exhibit weak mutagenic activity, but they considerably alter the transcriptional landscape of the DNA of exposed individuals.
[40][43] Malignant transformation of cells in a benign tumor may be detected by pathologic examination of tissues.