Genetic epidemiology of cancer predisposition DNA repair genes is probably related with ancestral surviving under adverse environmental conditions.

Abstract

Surviving under a stressful environment may be a real challenge. Individuals (and their offspring) with accumulated genetic variation in their DNA repair genes may have a higher probability to survive under these conditions. A partially unstable DNA repair system raises the mutagenesis rate and the probability for an advantageous mutation to appear. This can also explain the high incidence of specific types of cancer today. The aim of this study was to find evidence for this phenomenon in humans, trying in this way to explain the cancer rates that differ worldwide and especially the breast and colon cancer ones. The last ice age (last glacial maximum) is probably the most recent example of extreme environmental conditions that existed in many regions of our planet. Careful comparison of the last ice age Earth map with the cancer incidence maps of the GLOBOCAN project revealed a high similarity. Human populations that survived in those regions may indeed have a partially defective DNA repair system. Adding on to this observation, an evolutionary model is proposed here for how populations escape extinction, where cancer may have been increased in modern humans due to an evolutionary site effect. A novel explanation is proposed for the high cancer incidence in specific geographic regions, based on epidemiological observations and on the assumption for unstable DNA repair in ancestral individuals.