Genetics of Cancer Resistance

Two of three humans never get cancer. Even the majority of heavy smokers remain cancer free. Is this a matter of chance, or are there cancer-resistant genotypes?

Genetics play an important role in cancer. Not seldom the same types of cancer runs in families. Genetics tries to identify which features are inherited, and work out the details of how these features are passed from generation to generation. Genetic information is carried by a long molecule called DNA which is copied and inherited across generations.Traits are carried in DNA as instructions for constructing and operating an organism. These instructions are contained in segments of DNA called genes.

Different forms of one type of gene are called different alleles of that gene. Mutations are random events that change the sequence of a gene and therefore create a new allele. Cancer can be favored by mutations or the allelic polymorphism of many genes involved in the control of cell differentiation or division. These mutations and alleles can be part of the cause by which cells start dividing without control, even against the host of these cells, the human body. The question is whether cancer resistance is just the low occurrence of these mutations or cancer favoring alleles.

Alternative explanations for cancer resistance are:

• Cancer resistance can be induced in mouse strains. Low cancer strains can established with equal ease by selection. Besides a low tumor incidence some strains are highly resistant to most chemical carcinogenesis protocols. These strains carry multiple tumor resistance genes has been confirmed by the mapping of several loci that convey resistance at different stages of skin and lung tumor development
• Epidemiological evidence indicates that a significant proportion of the human population is highly resistant and that an equally significant fraction is highly susceptible to cancer
• Efficient immune rejection of tumors requires T-cell clones with specific receptors that can target non-self proteins. This immunological rejection is one of the mechanisms against cancer cells and viruses.
• DNA repair is a robust protection mechanism against cancer, it is also clear that there are individual variations in the efficiency of its many components.
• Both DNA damage and illegitimate activation of oncogenes can trigger apoptosis through a variety of pathways. This way “killing” activation of cancer genes and thus prevent cancer growth.
• Intercellular Surveillance is a mechanism or, more appropriately, a conglomerate of mechanisms. It has been well documented, but its genetics have not been investigated. This mechanism is that normal cells could inhibit the growth of neighboring polyoma-transformed cells by direct contact. Furthermore, there is a certain ‘‘hierarchy’’ in the ability of different transformed cells to inhibit each other and to be inhibited by normal cells.These contactual interactions between normal and tumor cells may be at least partly responsible for the frequent observation that the majority of most disseminated tumor cells never grow into metastases
• A large series of somatic hybrids generated by the fusion of normal with tumor cells for tumorigenicity in vivo showed that tumor growth was suppressed with these hybrids.

The genetics of tumor resistance, responsible for the protection of the majority of individuals against cancer development, is the great terra incognita of cancer genetics

But looks promising to me, what do you think?

G. Klein (2009). Toward a genetics of cancer resistance Proceedings of the National Academy of Sciences, 106 (3), 859-863 DOI: 10.1073/pnas.0811616106