The majority of cancers are not inherited. Cancer is, however, a disease of altered gene expression that originates in changes to DNA, the carrier of genetic information. For a cell to be transformed from normal to cancerous, it has to acquire different phenotype characteristics that result from alterations to the genotype. Most cancers develop to the stage of being clinically identifiable only years or decades after the initial DNA damage.
Cancer development, or carcinogenesis, requires a series of cellular changes. No single gene causes cancer. It is a multistep process caused by accumulated errors in the genes that control cellular processes. One genetic mutation may allow a single trait (such as increased survival) to be acquired by a lineage of cells and descendants of these cells may then acquire additional genetic mutations. However, cancer only develops when several genes are altered that confer growth and survival advantages over neighboring normal cells.
The capacity of a cell to achieve effective cancer prevention or repair is dependent on the extracellular microenvironment, including the availability of energy and the presence of appropriate macro- and micronutrients. Tumors are not simply masses of cancer cells. Rather, they are heterogenous collections of cancer cells with many other cell types-so called stromal cells; cancer cells communicate with stromal cells within the tumor. The tumor microenvironment comprises many cell types including infiltrating immune cells such as lymphocytes and macrophages, endothelial cells, nerve cells, and fibroblasts. All these cell types can produce growth factors, inflammatory mediators, and cytokines, which can support malignant transformation and tumor growth, and attenuate host responses. In addition, factors produced by the cancer cells themselves modulate the activity and behavior of the tumor stroma.
Initiation is the exposure of a cell tissue to an agent that results in the first genetic mutation. This can be an inherited mutation or an exogenous or endogenous (produced through oxidative metabolism) factor. Even without external oxidative stress, hundreds of sites within DNA are damages each day but are normally repaired or eliminated.
Exposure to the carcinogen initiates DNA damage, usually via the formation of DNA adducts. If left uncorrected, these adducts can be transferred to daughter cells during division and confer the potential for neoplastic (new and abnormal) growth.
Initiation alone is insufficient for cancer to develop. An initiated cell must go through a process of clonal expansion during promotion to become neoplastic; the larger the number of initiated cells, the greater the risk of progressing to cancer. Promotion involves exposure of the initiated cell to a promoting agent. This may allow alterations in the rate of proliferation or additional DNA damage to occur, leading to further mutations within the same cell, which alter gene expression and cellular proliferation. Finally, these initiated and promoted cells grow and expand to form a tumor mass. DNA damage continues at this stage and cancer cells often contain multiple copies of chromosomes. This clear, sequential process is typical of experimentally induced cancers but may be less clear in sporadic cancers in humans.
Figure 1. The six hallmarks of cancer. Cancer cells have different charecteristics from normal cells. The six hallmarks shown here are the phenotypic changes that need to be accumulated over time as a result of genetic changes (mutations and epigenetic factors) in order for a cell to become cancerous.
At the end of multistage process of carcinogenesis, the cell will bear some or all of the hallmarks of cancer (Figure 1). Several genes can contribute to each hallmark and one gene (for example p53) can contribute to several of the hallmarks. These hallmarks or traits are shared by most, if not all, cancer cells. The six hallmarks of cancer cells are self sufficiency in growth signals; insensitivity to antigrowth signals; limitless replicative potential; evasion of apoptosis; sustained angiogenesis; and tissue evasion and metastasis. Food, nutrition and physical activity related factors influence cellular processes and lead to cells accumulating these traits (Figure 2). The figure 2 describes the strength of evidence for suggesting relationships between numerous factors that enhance or reduce cancer risks.
Figure 2. The influence of food, nutrition, obesity and physical activity on the processes of cancer.
Reference: World Cancer Research Fund International and the American Institute for Cancer Research released reports.
