Do Genes and Gender Play a Role in Chemotherapy-Related Fatigue?

While fatigue is one of the most common side effects of chemotherapy treatment, recent research suggests that genetics may play a role, making certain patients with cancer more prone to fatigue than others.

The study, which was published in the journal Supportive Cancer Care, included 333 adult patients who had breast, gastrointestinal, gynecologic or lung cancers. All participants received chemotherapy within the past four weeks, and had at least two more chemotherapy treatments scheduled in the future.

A grading system called the Lee Fatigue Scale was used to rank the patients’ evening fatigue levels. They rated 13 items from zero to 10 each night before bed, comparing their feelings to the previous week. The higher the rating, the more severe their fatigue was.

In total, 65 patients fell into the “moderate fatigue” group, while 195 fell into the “very high fatigue” group. No patients involved in the study had low levels of fatigue, according to the authors. Those who had very high levels of fatigue were more likely to have alterations in genetic pathways that controlled immune function, inflammation, neurotransmission, energy metabolism and circadian rhythm.

There is currently no cure for chemotherapy-related fatigue, and exercise is the only proven intervention that can help decrease fatigue levels in survivors.

“We were surprised with the identification of two previously undescribed mechanisms underlying fatigue, which include renal function and carbohydrate metabolism,” Elena Flowers, Ph.D., RN, study author and assistant professor at the School of Nursing at University of California San Francisco said in an interview with CURE.

Further, some patients — particularly those who were women and/or have breast cancer — showed to be more likely to experience high levels of fatigue than others.

Flowers mentioned that women report higher levels of not only fatigue, but most other cancer symptoms, too. However, why this association occurs is not completely understood. “It may be that women have additional responsibilities (e.g. caring for children) that increase their level of fatigue,” she said. “Additional research is needed to determine the causes for increased fatigue in these women.”

But regardless of gender or cancer type, the authors emphasized that since 30 percent of survivors experience extreme fatigue, it is vital that researchers develop a better understanding of the symptom and create personalized approaches to ease the burden in survivors.

“Given the high occurrence rate and significant negative impact of fatigue on patients’ lives, it is imperative that effective treatments be developed for this devastating symptom,” the authors wrote.

While the findings of this study do not have direct implications for clinical practice at this time, the authors hope that eventually interventions can be created that will target the pathways they found to be associated with higher levels of chemotherapy-related fatigue.

In addition to studying gene expression, the authors are also examining epigenetic markers, which can point out changes in gene expressions that are not a result of variation in genetic sequences.

“Epigenetic mechanisms help patients adapt to changes in their environment, including factors like chemotherapy and stress,” Flowers said. “We hope that the integration of gene expression with epigenetics will elucidate a more comprehensive biological model for fatigue.”