Studies of genetic connections can be represented by gene-environment and gene-gene interaction studies. These classes of genetic relationships focus on understanding how human genetic variability can be linked to a variety of responses to exposures to different environmental aspects. These effects can also vary depending on differences in other genes.
Gene-environment interactions can be highlighted through recent studies which identify genetic mutations. An example of the gene-environment association can be seen in the different responses to exposure to cigarette smoke and its connection to lung cancer. For instance, it has been proven that tobacco smoke contains a wide variety of chemical carcinogens which may cause damage to DNA.This damage is repaired by several DNA pathways.
These gene-gene interactions and pathways contain genes which provide researchers with information to understand why certain smokers develop lung cancers, while others do not. In a 2003 study, researchers examined the variations in two genes that are associated with DNA repair. They examined these genes to identify their potential relationship with the level of cigarette smoking and the connection to lung cancer.
They found that one putatively functional mutation of the XRCC1 (X-ray cross-complementing group 1) gene and two putatively functional mutations in the ERCC2 (excision repair cross-complementing group 2) gene were genotyped in 1,091 lung cancer cases and 1,240 controls.
When these cases and controls were organized by heavy smokers and nonsmokers, they found that nonsmokers with the mutant XRCCI genotype had a 2.4 times greater risk of developing lung cancer than nonsmokers with the normal genotype. However, heavy smokers with the mutant XRCCI genotype were 50 percent less likely to develop lung cancer than heavy smokers with the regular genotype.
Additional mutations were examined using extreme genotypes, individuals with five or six mutations present in their genotype. Researchers found that when three mutations were from these two genes were examined together in the extreme genotypes, they were 5 times more likely to develop lung cancer than nonsmokers.
Furthermore, there was a 70 percent reduction in the risk of developing lung cancer for heavy smokers compared to individuals with no mutations. Researchers believe that the protective effect of the heavy smokers’ genetic variation was caused by the differential increase in the activity of the protective genes. The protective genes were stimulated by heavy smoking.
Examination of the ERCC1 also demonstrated similar types of gene-smoking interactions. This relationship has also been found in other genes in this pathway. All of these studies highlighted the importance of identifying genetic variations which are associated with risks of diseases related to human behavior.
While this research provided valuable insights to gene interactions and behavior relationships, it also raises ethical and social questions due to the fact that it identifies susceptible and protected subgroups of subjects by both genetic and behavioral classes of people.
Studies on Gene-Gene Interactions and Effects of Mutations
These studies also provided additional information by jointly examining the effects of multiple mutations on the toxicity-related disease.There have also been studies involving the mutation of genes involved in the Phase II metabolism. These studies have revealed the importance of investigating the joint effects of mutations and their connection to cancer risks.
While the majority of these studies primarily focused on the additive effects of multiple genes, it is also important to notice gene-gene interactions. These interactions are an important part of developing a deeper understanding of human’s susceptibility to diseases as well as their interactions with the environment.
The role of gene-environment and gene-gene interactions are essential for understanding one’s susceptibility for developing diseases. In order to fully understand the pattern of genetic susceptibility to environmental factors that impact public health, more studies on the effects of joint multiple mutations must be conducted. One of the key aspects of these studies is the role of bioinformatics.
For instance, the screening of SNP databases for mutations in transcriptional regulatory regions can be used for discovery as well as functional validation of polymorphic regulatory elements. This includes the antioxidant regulatory element found in the promoter regions of many genes encoding antioxidative and Phase II detoxification enzymes.