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June 2, 2009

New model of cancer development proposed

New model of cancer development proposed

In an article scheduled to appear in the Annals of Epidemiology, epidemiologist Cedric Garland, DrPH and his associates at the University of California San Diego's Moores Cancer Center propose that cancer, rather than commencing with genetic mutations, is initially caused by a reduction in the of ability of cells to stick together.

Research has shown that inadequate vitamin D can result in a loss of stickiness between cells as well as a loss of differentiation, which causes cells to revert to a stem cell-like state. Additionally, extracellular calcium ions are necessary for intercellular adherence.

"The first event in cancer is loss of communication among cells due to, among other things, low vitamin D and calcium levels," explained Dr Garland, who is a professor of family and preventive medicine at the UC San Diego School of Medicine "In this new model, we propose that this loss may play a key role in cancer by disrupting the communication between cells that is essential to healthy cell turnover, allowing more aggressive cancer cells to take over."

Dr Garland's model is summarized by the acronym DINOMIT, which stands for progressive phases of cancer development: disjunction (loss of intercellular communication), initiation (in which genetic mutations begin to be involved), natural selection of the most rapidly reproducing cancer cells, overgrowth, metastasis, and two dormant states known as involution and transition.

"Competition and natural selection among disjoined cells within a tissue compartment, such as might occur in the breast's terminal ductal lobular unit, for example, are the engine of cancer," Dr Garland stated. "The DINOMIT model provides new avenues for preventing and improving the success of cancer treatment."

"Vitamin D may halt the first stage of the cancer process by re-establishing intercellular junctions in malignancies having an intact vitamin D receptor," Dr Garland noted. "Vitamin D levels can be increased by modest supplementation with vitamin D3 in the range of 2000 IU/day."

Dr Garland has authored several studies concerning the relationship between low sunlight exposure and vitamin D levels with an increased risk of breast, colorectal, ovarian and kidney cancers. He notes that over 200 epidemiological studies have associated certain cancers with reduced vitamin D. Mechanisms cited for vitamin D and calcium in lowering cancer incidence and mortality include upregulation of adherence and signaling between epithelial cells, contact inhibition of proliferation, differentiation, cell cycle stabilization, apoptosis promotion, anti-angiogenesis, and various effects on proteins involved in the development of cancer.

"The time has arrived for nationally coordinated action to substantially increase intake of vitamin D and calcium," the authors conclude.

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Health Concern Life Extension Highlight

Breast Cancer

Breast cancer occurs when cells in the breast tissue divide and grow without control. The cell cycle is the natural mechanism that regulates the growth and death of cells. When the normal cell regulators malfunction and cells do not die at the proper rate, there is a failure of cell death (apoptosis) therefore cell growth goes unchecked. As a result, cancer begins to develop as cells divide without control, accumulating into a mass of extra tissue called a tumor. A tumor can be either non-cancerous (benign) or cancerous (malignant). As a tumor grows, it elicits new blood vessel growth from the surrounding normal healthy tissues and diverts blood supply and nutrients away from this tissue to feed itself. This process is termed “angiogenesis”- the development (genesis) of new blood vessels (angio). Unregulated tumor angiogenesis facilitates the growth of cancer throughout the body.

Cancer cells have the ability to leave the original tumor site, travel to distant locations, and recolonize. This process is called metastasis and it occurs in organs such as the liver, lungs, and bones. Both the bloodstream and lymphatic system (the network connecting lymph nodes throughout the body) serve as ideal vehicles for the traveling cancer. Although, these traveling cancer cells do not always survive beyond the tumor, if they do survive, the cancer cells will again begin to divide abnormally and will create tumors in each new location. A person with untreated or treatment-resistant cancer may eventually die of the disease if vital organs such as the liver or lungs are invaded, overtaken, and destroyed.

Vitamin A and vitamin D3 inhibit breast cancer cell division and can induce cancer cells to differentiate into mature, noncancerous cells. Vitamin D3 works synergistically with tamoxifen (and melatonin) to inhibit breast cancer cell proliferation. Pre-clinical studies demonstrated that vitamin D compounds could reduce breast cancer development in animals. Furthermore, human studies indicate that both vitamin D status and genetic variations in the vitamin D3 receptor (VDR) may affect breast cancer risk.

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