Doctors' Take On Whether Long Telomeres May Lead To Cancer

Headlines surrounding long telomeres potentially causing more harm than good in terms of longevity have been in the spotlight. For good reason, since earlier this month researchers published a new study in The New England Journal of Medicine reporting their findings that ultra-long telomeres might not promote longevity as previously thought. On the contrary, it may increase the risk of blood conditions and cancer.

We talked to an oncologist and a clinical doctor to find out what the connection was between super long telomeres and cancer. Additionally, should us long-life seekers change our minds about biohacking our biology to lengthen the caps on the end of our DNA?

About the study

The study investigated the connection between carrying the POT1 gene mutation and the risk of developing clonal hematopoiesis, a blood condition that increases the chance for heart disease and cancer.

Over the course of the two-year study, the Johns Hopkins researchers looked at 17 individuals who carried the POT1 gene and 21 of their relatives who did not. While the relatives had the typical telomere shortening with age, the gene carriers maintained telomere length that was described as ultra-long.

In normal conditions, the POT1 gene is linked to longer telomeres. However, mutations of this gene may result in ultra-long DNA end caps. Out of the 17 individuals, telomere length was assessed for 13 participants. In all cases, their telomeres were 90% longer compared to the average population, and nine individuals had telomeres longer than 99% of the general population.

Researchers concluded that mutations in the long telomere group may lead to an increased risk of blood cancers in adulthood.

Is the connection legitimate?

“As early as the 2000s, we have established that telomere capping and telomerase activity have an active role in cancer formation,” Dr. Danielle Leonardo, oncologist, told Healthnews in an interview. “The function of the POT1 gene is to protect telomere ends from DNA damage and mutation, and so (loss-of-function) mutations of the POT1 gene will render normal DNA to be susceptible to damage, which increases the risk for malignant diseases.”

A study in 2020 discussed how POT1 tumor predisposition increases the risk of different cancers, including skin cancer, chronic lymphocytic leukemia, thyroid cancer, glioma (a specific type of brain tumor), and more. While the majority of these conditions are diagnosed in adulthood, the predisposition is genetic and can be inherited from a parent.

Since people with POT1 mutation tend to have longer chromosomes, they are not only exposed to DNA damage and mutation, but also have longer lifespans, increasing the chances that acquired DNA mutations can eventually cause cancers.

To put it in perspective, Dr. Leonardo explained, “If a chromosome, for example, contains the BRCA1 gene mutation that causes breast cancer, and this chromosome happens to have a long telomere length, the chromosome is said to "live longer." This gives the BRCA1 mutation more time to develop into tumors.”

The interplay between genetics and lifestyle

In the realm of longevity and health optimization, it’s often said that “genes are not our destiny," and that epigenetics, or lifestyle choices, play a critical role in gene expression. How would this relate here?

"While telomere length is primarily influenced by genetic factors, environmental factors and lifestyle choices such as smoking, diet, exercise, and stress levels can also impact telomere maintenance and function."

Dr. James Walker, clinical doctor

Epigenetic modifications, which can be influenced by lifestyle choices, can affect gene expression patterns and potentially contribute to the development of cancer.”

Lifestyle, however, isn’t always enough. Dr. Leonardo pointed out, “Of course, lifestyle choices have been proven to increase or decrease a person's cancer risk, but we have seen patients develop cancer despite living a healthy lifestyle, and this is because of other genetic risk factors coming into play.”

Screening and prevention

There are several different DNA tests available today which makes it possible for anyone to find out if they carry a POT1 gene mutation. A swab sample is enough to determine if someone has a pathogenic mutation or a variant that is likely pathogenic in the POT1 gene. Additionally, it can provide data if they have an increased risk to develop cancer.

"There haven't been screening and early interventions proven to prevent cancer occurrence or improve survival.”

"Unfortunately, we do not have robust evidence yet on how we can prevent the development of cancer among POT1 gene mutation carriers"

Dr. Leonardo

She did provide suggestions to best manage should a POT1 gene mutation be found:

• Refer the patient to a genetic counselor in order to better determine what possible tumors the patient is at risk of. Also, a genetic counselor can help assess if other members of the family are at risk and would need screening.
• Emphasize lifestyle changes: maintain a healthy body mass index, have an active lifestyle, eat more fruits/vegetables, decrease red meat intake to not more than two servings a week, smoking cessation, alcohol abstinence, routine adult vaccinations, etc.
• Although there are no well-developed screening protocols, a more proactive wellness check is advised among POT1 gene mutation carriers, such as annual skin checks, blood exams, and routine imaging studies.

Can long telomeres be a problem?

Like many things regarding increasing healthspan and lifespan, more isn’t necessarily better. It’s about finding just the right amount, whether it’s exercise, stress, fasting, or cold exposure.

The same is true for telomeres, especially if one carries the POT1 gene. “Long telomeres among patients without the POT1 gene or any oncogene for that matter, we can say, have lower chances of developing cancers, because the telomere caps are intact, protecting the chromosomal ends from damage,” Dr. Leonardo said, highlighting that longer telomeres, however, may also mean that there are more chances of DNA replication where point mutations can occur (regardless of POT1 mutation). "Cancer can still occur here. Telomere length therefore can have its advantages and disadvantages.”

This study may impact how people seeking longevity view telomeres by highlighting the importance of maintaining a balance in telomere length.

“While short telomeres are associated with aging and age-related diseases, excessively long telomeres, particularly in the presence of certain gene mutations, can also have negative consequences,” Dr. Walker said emphasizing the need for a comprehensive understanding of telomere biology and the potential risks and benefits associated with telomere lengthening strategies.