In a new study entitled “Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study,” researchers report that long telomeres are associated with an increased risk of lung adenocarcinoma. The findings were published in the Human Molecular Genetics journal.
Telomeres are the caps at the end of each strand of DNA, and are fundamental in protecting our chromosomes from damage. In each cell division, a small portion of telomeres is lost leading to telomere shortening, a phenomenon associated with aging and cardiovascular diseases. Notably, however, telomere length and its association with cancer is still unclear. The main reason is that factors, including age, lifestyle and cancer progression can significantly influence telomere length and cloud researchers conclusions.
In this new study, a team of scientists from University of Chicago employed a new method to avoid such biases, the Mendelian randomization approach, in which researchers determined the associations between genetic determinants of telomere length (previously identified in genome-wide association studies) and the risk for cancer. This approach allows no biases, since the genetic determinants remain unchanged even if telomeres length changes due to other factors.
The team used data from the GAME-ON (Genetic Associations and Mechanisms in Oncology) network, and analyzed more than 50,000 cancer cases and 60,000 controls. They then determined the risk for developing breast, lung, colorectal, ovarian and prostate cancers based on telomere length. They found a significant increase in risk for developing lung adenocarcinoma (a specific type of lung cancer), with an increase of 1000 base pair in telomere length leading to double of cancer risk. Notably, with other types of cancer the team found no association between telomeres length and cancer risk.
Study lead author, Brandon Pierce, PhD, assistant professor of public health sciences at University of Chicago commented, “Our work provides compelling evidence of a relationship between long telomeres and increased risk for lung adenocarcinoma. The prevailing hypothesis has been that short telomeres are bad for health, but it appears that this does not necessarily translate to some types of cancer.”
Chenan Zhang, study first author and a graduate student in public health sciences at University of Chicago added, “Mendelian randomization is an important tool that allows us to examine telomere length without the problematic biases that come with physically measuring it. The positive association between telomere length and lung adenocarcinoma should be further investigated with the long term goal of improving prediction and prevention of this common cancer subtype.”
Although authors recognize that Mendelian randomization can also be subject of bias, researchers believe that if genetic variants independently affect cancer risk and telomere length, they offer significant advantages when compared to other methods and identifies new associations that may lead to new therapeutics, as Dr. Pierce noted, “The complex relationship between telomeres and cancer risk is one that we need to further understand. This study gives us an estimate of a causal relationship that could serve as a guidepost for the development of interventions in the future.”