High altitude and cancer: An old controversy

•Cancer prevalence and mortality is lower in high altitude populations of the United States and China, but higher in high altitude dwellers of Ecuador and India.•Some genetic and molecular modifications that allow for chronic hypoxia tolerance are known to facilitate oncogenesis.•Lung cancer, lymphoma, colon cancer, esophageal carcinoma may have a decreased incidence at high altitude.•Gallbladder and biliary duct cancer, stomach carcinoma, skin cancer may be more frequent at high altitude. Ecological studies have found that individuals that live at high altitude regions and in places where ultraviolet radiation is maximal, have lower rates of different types of cancer. However, there is evidence that in these same regions, genetic mutations that are prooncogenic, develop, as they are needed to increase human adaptability to hypoxic environments. Debate has arisen between researchers who consider high altitude environments as suitable for human longevity because of its protective effects against malignancies, and scientists that have reported an increased incidence of different type of cancers in these same regions. Evidence is presented that altitude is related to the development of genetic alterations in micro RNAs, p53 protein, lymphocyte activity, decrease in Fas Ligand and other proapoptotic molecules, as well as increase in prometastatic VGEF an HIF. Notwithstanding, higher vitamin D and ultraviolet B levels, and a better metabolic profile, taken together with lower pollution levels hves been related to lower incidence and mortality rates from malignancies in a series of epidemiological studies.