Cancer is only a rare (10% to 15%) complication of the so-called short telomere syndromes, which consist of a series of clinical presentations which can manifest from infancy (immunodeficiencies, bone marrow failure, enteropathies, idiopathic pulmonary fibrosis, emphysema, and liver diseases) associated with telomerase and telomere maintenance genes mutations. Probably, in the case of degenerative diseases, and not cancer, they are the predominant consequences of telomere shortening because in most patients with short telomere syndromes the DNA damage response is intact. Other mutations influencing telomere elongation are associated with the socalled long telomere syndromes, which are associated with familial cancer. Longer telomeres resulting from these mutations confer a longevity advantage and may permit an increased replicative potential of cells acquiring mutations that would otherwise undergo cell death, thus, promoting cancer development.
The most prevalent cancers in the carriers of these hTERT and shelterin genes mutations are melanoma and chronic lymphocytic leukemia. However, even if such mutations were identified in familial forms of a specific cancer, people carrying it showed other malignancies, too. This suggests that this kind of alteration confers a broader cancer-prone state. Furthermore, other mechanisms have been suggested associating longer telomeres with cancer. In the case of breast cancer, a hormonerelated disease, reports of longer telomeres in women than men, and in postmenopausal women with hormone replacement therapy suggest that estrogen might play a role in determining telomere length in breast cancer. Moreover, telomere length maintenance might be promoted by the antioxidant capacity of estrogen. Finally, it has been suggested that in renal cell carcinoma the downregulation of the immune response might reduce telomere attrition, leading to longer telomeres.
