Genetic Sensitivity to Stress: A Possible Link to Lung Cancer Risk

It’s common knowledge that stress can affect physical and mental health, but does it impact the chance of developing lung cancer? The answer might be yes, according to a study published last month in JAMA Network Open. The results point to a possible connection between stress sensitivity and lung cancer risk, with individuals who are genetically more sensitive to stress and adversity possibly facing a higher risk of developing lung cancer.

Sensitivity to stress is a personality trait that tends to run in families. Stress, whether from outside events or internal pressures, causes the body to release stress hormones like adrenaline, which affects metabolism, immune health, and other important body functions.

To explore the effects of stress on lung cancer, a team of researchers, including first author Yingxi Chen, M.D., Ph.D., scientist at the Division of Cancer Epidemiology & Genetics at the National Cancer Institute, examined data from more than 350,000 individuals in the UK Biobank and 61,000 lung cancer cases across different populations.

The researchers used Mendelian randomization, a method that relies on genetic data to assess disease risk while controlling for other factors. The study specifically looked at different types of lung cancer, including small cell lung cancer, squamous cell carcinoma, and lung adenocarcinoma.

The genetic proxies used in the research were mainly linked to neuroticism, which the authors describe as a broad category of personality traits marked by a tendency toward emotions like guilt, embarrassment, and being easily hurt. Assessments of emotional reactivity were measured through questions like: “Are your feelings easily hurt?” “Do you worry too long after an embarrassing experience?” and “Are you often troubled by feelings of guilt?” For the analysis, the researchers chose 4,463 genetic markers linked to sensitivity to stress and also found in lung cancer outcome dataset.

The analysis revealed that genetic sensitivity to stress was linked to a 49% higher risk of lung cancer in people of European ancestry, and a 45% higher risk in a broader group. The findings also showed that those genetically predisposed to stress sensitivity were at higher risk not only for the onset of lung cancer but also for its progression.

Interestingly, the relationship between stress sensitivity and lung cancer subtype risk was not the same across all populations. In people of European ancestry, the association was strongest for squamous cell carcinoma. For East Asian populations, the link was more pronounced in adenocarcinoma. However, no significant relationship was found in people of African ancestry. These differences highlight the complexity of lung cancer development, which is influenced by a combination of genetic, environmental and lifestyle factors.

“Prolonged exposure to stress is particularly concerning, as it can lead to enduring changes in emotional, physiological, and behavioral responses, thereby increasing individuals’ susceptibility to various health conditions,” the authors wrote in their paper.

Although the study offers valuable insights, the authors acknowledged several limitations. For instance, the genetic proxy of “neuroticism” might not fully capture all the different ways people experience stress. Additionally, the sample sizes for some populations were limited, which could affect the accuracy of the findings for those groups.

“These results not only contribute to our understanding of lung cancer’s multifaceted nature but also underscore the necessity for further research into the nuanced association between psychosocial stress and cancer risk, with a particular focus on diverse populations,” the authors concluded.

Understanding how stress contributes to cancer risk could help healthcare providers identify patients at higher risk and recommend preventive measures, especially in populations genetically predisposed to stress-related health issues.