The population of childhood cancer survivors in the U.S. is increasing, with an overall childhood cancer survival rate greater than 85% five years after diagnosis. However, survivors can still be at increased risk of various health conditions, including second cancers.

Using data from the Childhood cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (St. Jude Life), scientists at St. Jude Children’s Research Hospital have identified a genetic explanation for why a small proportion of survivors is more likely to develop second cancers and why these cancers may be more severe or deadly.

The findings, which will inform genetic counseling, testing and adoption of personalized cancer screening and prevention strategies, were published today in The Lancet oncology.

The St. Jude group showed that survivors with pathogenic (damaging) genetic variants in specific genes, called cancer-predisposing variants, are at an increased risk of developing second (subsequent) cancers as adults, and those cancers are more likely to be severe and deadly.

The scientists had previously identified that survivors with pathogenic variants in one of 60 different cancer-predisposing genes or 127 DNA damage repair genes were more likely to experience a second or subsequent cancer. This study extends that research to show a direct connection between cancer-predisposing variants and increased second-cancer-related mortality.

Many of these genetic variants are known to be causally linked to cancers. For example, the tumor suppressor gene TP53 is one of the 60 genes included in the analysis. The key to the discovery’s utility is that these variants are present in the DNA of patients when they are diagnosed with cancer as children, allowing for an individualized medicine approach to be developed early in life for each survivor.

By promoting better understanding of the effect such genes can have on future cancer risk and its outcome beyond the primary childhood cancer, the study will help inform efforts to prevent second cancers and improve the outcomes in these individuals.

“Our study pinpoints that clinical genetic testing to screen for and identify if survivors are carriers of these pathogenic variants could lead to screening and early interventions for those at higher risk to develop deadly second cancers, potentially saving their lives,” said senior corresponding author Zhaoming Wang, Ph.D., St. Jude Department of Epidemiology and cancer Control.

cancer prevention in adult childhood cancer survivors

The total number of childhood cancer survivors who develop second or subsequent cancers is small (<10% based on current studies), and the percentage of survivors who carry cancer-predisposing variants is low (about 6%). Together, these factors have made it extremely challenging to study and understand the genetic risks for second cancers and their outcome in this population.

To reach statistically meaningful results, Wang and his collaborators combined whole genome/exome sequencing and clinical data from over twelve thousand survivors of childhood cancer. The study combined data from North America’s two largest survivorship studies, the CCSS and St. Jude LIFE cohorts.

“This is the first comprehensive study looking for the genetic reason for late mortality—specifically late mortality due to second cancers,” Wang said. “Now we know that cancer-predisposing variants contribute to the risk of death from second cancer.”

Increased surveillance may help limit the impact of these cancer-predisposing variants as childhood cancer survivors grow into adulthood. By knowing which survivors are at greater risk, health care providers may be able to recommend personalized cancer screening, which may lead to the detection of additional cancers at their earliest and most treatable stage.

These variants are part of the inherited (germline) DNA with which people are born. This means they can be detected in children when they are first diagnosed with childhood cancers, arming survivors with the knowledge they need to lower their risk later in life.

“Even before finishing childhood cancer treatment, clinicians can recommend referral to do genetic counseling so that survivors with these variants can seek cancer prevention strategies later on,” Wang said. “Depending on the gene harboring the variant, survivors that are carriers may be able to implement prevention strategies to safeguard their long-term health.”

Alexandre Chan, PharmD, MPH is a chair and professor of clinical pharmacy at University of California, Irvine (UCI). He is affiliated with the UCI Chao Family Comprehensive cancer Center as well as the National cancer Centre Singapore. Dr. Chan has worked with people with cancer for almost 20 years, and he has conducted a wide array of research in supportive care, toxicities management, and cancer survivorship. Quinton (Ding Quan) Ng, BS (Pharm)(Hons), is a PhD Candidate at UCI and a registered pharmacist from Singapore. Mr. Ng’s research expertise spans across domains of epidemiology, biostatistics, and biomarker analysis, with a primary focus in treating and preventing adverse health outcomes in people with cancer. You can follow Dr. Chan and Mr. Ng on X, formerly known as Twitter. View disclosure information for Dr. Chan. Mr. Ng has no relationships to disclose.

Over the past decade, the use of electronic cigarettes, also called e-cigarettes or vaporizers, has become a popular substitute for tobacco products in people looking to quit smoking. You may hear the use of e-cigarettes more commonly referred to as “vaping.” However, there is a growing amount of research to suggest that e-cigarettes contain many harmful substances, including chemicals that can cause cancer. In one study conducted by the Centers for Disease Control and Prevention (CDC), it was found that almost all the e-cigarettes sold within the United States during the study contained nicotine.

Vaping has become especially common among young people, as flavored e-cigarettes and strong marketing tactics have been used to make vaping more appealing to teens and young adults. This could be problematic, as one survey showed that teenaged e-cigarette users were 2 times more likely to smoke tobacco cigarettes compared to those who had never used e-cigarettes. These are worrisome trends as e-cigarettes continue to gain tremendous popularity, particularly among younger people.

It is important to know that e-cigarettes are not currently approved by regulatory authorities, including the U.S. Food and Drug Administration (FDA), as a method to help people stop smoking. Even more importantly, questions regarding the long-term health problems of vaping in people with cancer and survivors remain unanswered at this time. If you are using or considering using e-cigarettes during cancer or survivorship, it is important to talk with your health care team about how vaping could affect your overall health.

What are the negative health effects of vaping?

There is a common belief that e-cigarettes are safer than traditional cigarettes, but it’s important to know that studies involving the long-term use of e-cigarettes have shown that they can negatively impact brain and heart health. E-cigarette vapor also contains many harmful chemicals that are released during the heating of the liquid propylene glycol or glycerin, which are commonly used to dissolve the active nicotine ingredient found in vaping products. Nicotine in e-cigarettes may also negatively impact brain development and lead to addiction in children, teens, and young adults.

As e-cigarettes are a fairly new phenomenon, our knowledge on their long-term health effects is relatively lacking at this time. Human studies with follow-up periods longer than 5 years are needed to better understand how e-cigarette use may impact the health of people with cancer and survivors. In fact, the American Society of Clinical oncology and the American Association for cancer Research have called for more research to be done on e-cigarette products, including around their potential health impacts.

Regardless, because of the toxic substances found in e-cigarettes, people with cancer and survivors should talk with their health care team about avoiding using e-cigarettes as a quitting-smoking tool or as a remedy to reduce stress or improve attention, thinking, or memory problems until more is known about the effects of e-cigarette usage.

What does the research say about vaping and cancer?

Many people with cancer may turn to using e-cigarettes because they think it could help them stop smoking. In one study published in Psychooncology, people with cancer expressed their preference for e-cigarettes over nicotine replacement therapy as a treatment for quitting smoking. However, over 70% of people with cancer who used e-cigarettes reported that they did not inform their cancer care provider that they used e-cigarettes.

Several other studies have evaluated the patterns of e-cigarette usage among cancer survivors. One study analyzed data of more than 8,000 cancer survivors from the National Health Interview Survey (2014–2018) and observed more e-cigarette usage among cancer survivors identifying as White compared to other racial and ethnic groups. Other studies have also observed that e-cigarettes are often used together with conventional cigarettes.

We recently studied the relationship between adverse health behaviors, including vaping, and cognitive problems in young adult childhood cancer survivors, which was published in JCO oncology Practice. Cognitive problems can include trouble with thinking, paying attention, and remembering things. Our study included 1,106 young adults who had survived childhood cancer who were ages 15 to 39 when they entered the study and were at least 5 years out from their cancer diagnosis. We observed that the use of e-cigarettes was 2 times higher among survivors with self-reported cognitive impairment compared to other survivors. Those cognitively impaired survivors were also found to have poorer physical and mental health. Although the exact reasons for vaping were not captured in the study, we speculated that these survivors were vaping for stress relief, smoking cessation, and potentially to seek improvement of short-term alertness and concentration.

Ultimately, it is important to always talk with your health care team before using e-cigarettes so they can help address any questions you may have around vaping.

What should people with cancer and survivors know about using vaping to help quit smoking?

For people with cancer and survivors who have quit smoking traditional cigarettes and are using e-cigarettes solely for smoking cessation, they should consider seeking the help of a pharmacist. Many community pharmacies provide smoking cessation services and can help redirect them to other evidence-based methods to stop smoking, including nicotine replacement therapies and medications such as varenicline (Chantix) and bupropion (Wellbutrin, Zyban). Talk with your health care team for a referral to a pharmacist who can help with smoking cessation.

Research is also currently ongoing to evaluate new strategies for improving the effectiveness of quitting smoking approaches, including individualized health educational programs, peer navigators, and mobile health applications to help people stick with their plans to quit.

Your pharmacist can work closely with you to personalize a quitting smoking plan that is best suited for your needs and lifestyle. Even if you are thinking about quitting but you are not fully ready, your pharmacist is still a great resource to turn to as you navigate this decision.