Maternally inherited susceptibility to cancer

Tumor microenvironment promotes mtDNA mutations. A number of these mutations will affect cell metabolism and increase cell survival. These mutations are positively selected and contribute to other tumor features, such as extracellular matrix remodeling and angiogenic processes, thus favoring metastases. Like somatic mutations, although with less marked effects, some mtDNA population polymorphisms will affect OXPHOS function, cell metabolism, and homeostasis. Thus, they could behave as inherited susceptibility factors for cancer. However, in addition to epidemiological evidence, other more direct clues are required. The cybrid approach can help to clarify this issue. This article is part of a Special Issue entitled: Bioenergetics of Cancer.

Research Highlights
► Tumor microenvironment promotes mtDNA mutations.
► Some mtDNA mutations can contribute to tumor features.
► Many tumor mtDNA mutations have been found as haplogroup-defining polymorphisms.
► MtDNA polymorphisms could behave as inherited susceptibility factors for cancer.
► Cybrids can be used to check the effect of cancer-associated mtDNA polymorphisms.