A tumor microenvironment with poor oxygen and nutrient supply is an important trigger of the angiogenesis process ( 11). One of the genetic pathways of particular interest in colon cancer outcomes is the angiogenesis pathway, which mediates the process of growing of blood vessels from existing ones to support tumor growth and progression. It is essential to focus on a biologic pathway relevant to the disease and environmental exposures relevant to the pathway. Such an approach ignores the inherent coordination among genes or their proteins, which is better captured by a pathway structure comprised of multiple genes with related biologic functions jointly contributing to risk in different environmental contexts ( 10). This does not take into account the possibility of interaction between individual genetic variants and will, thus, either fail to observe or detect only weak associations. The standard “marginal” analysis approach analyzes single nucleotide polymorphisms (SNPs) one at a time. This has reinforced the hypothesis that the large unexplained hereditary component of colon cancer risk referred to as “missing heritability” (by which is meant, more correctly, “missing explanations for familial aggregation”) may be partially explained by epistatic and/or gene-environment interactions (GEIs) ( 9). Although evidence on lifestyle/environmental exposures’ effects on colon cancer survival is limited, some evidence suggests pre- and/or postdiagnostic dietary patterns, smoking, and alcohol consumption may have an impact on colon cancer mortality ( 7).Ĭonsiderable efforts have been made to identify highly and moderately penetrant rare variants in association with colon cancer and, more recently, common low-penetrance risk alleles through genome-wide association studies (GWAS), with only modest success ( 8). Additional evidence comes from Japan, a country with historically one of the lowest incidence rates of colon cancer becoming one of the highest incidence rates in the world over several decades ( 1, 5, 6). Several lines of evidence indicate a prominent role of dietary and lifestyle factors in colon cancer etiology including wide geographical variations in incidence across countries ( 2) and migrant populations, especially of Asian descent, moving from low-risk to high-risk countries acquiring the host country’s high levels of risk ( 3, 4). Colon cancer is a multifactorial disease with well-documented genetic and nongenetic risk factors ( 1).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |