Study Finds Mutated Tau May Be a Susceptibility Factor for Cancer


Key Points

  • Mutations to the protein tau, which is commonly associated with neurodegenerative disorders, may have a novel role in the development of cancer.
  • 15% of subjects from tau-mutated families developed cancer, while only 9% of subjects from the reference families developed cancer. Individuals from tau-mutated families were 3.72 times more likely to develop cancer compared with the control families.
  • Additional research is needed to determine whether individuals with a tau mutation should be monitored for both neurodegenerative disorders and their risk for cancer.

Tau proteins perform the function of stabilizing microtubules, a major element of the eukaryotic cytoskeleton. Traditionally associated with neurodegeneration, tau also has a role in the maintenance of genome stability and chromosome integrity and is tightly linked to the development of cancer. A small retrospective cohort study comparing cancer incidence in families affected by a mutation in the tau gene (genetic tauopathies) to control families shows there may be a novel role for tau as a risk factor for cancer, providing new insights in the various pathological roles of mutated tau. 

The study by Rossi et al found that individuals from the tau-mutated families were 3.72 times more likely to develop cancer than individuals in the control families. The study is published in Cancer Research.

Study Methodology

The researchers analyzed cancer incidence in 15 families bearing seven different tau mutations and affected by frontotemporal lobar degeneration (FTLD). To calculate cancer risk, the researchers matched each tau-mutated family with three reference families with superimposable pedigrees, including the control subject’s age, gender, and native location.

Factors known or thought to influence cancer incidence, such as gender, year of birth, and region of origin, were initially analyzed by univariate Cox proportional hazard model.

Study Findings

The researchers found that within the tau-mutated families, 24 subjects (15%) had cancer, and within the reference families 68 subjects (9%) had cancer. The mean age at diagnosis of cancer was 58 years, while the average age of dementia onset was 50 years. Cancer types in both cohorts were variable; tau mutations were not associated with specific cancers.

The study showed that the tau-mutated families had significantly greater risk of cancer than the reference families (Hazard ratio [HR] = 3.11), and, when the gender variable was assessed, the risk in females appeared to be greater than in males, though not significantly (HR = 1.16). The researchers then performed multivariate Cox proportional hazard model to estimate HRs with 95% confidence intervals [CIs] of cancer events. The model was stratified by gender, year of birth and region of origin to control for potential confounding effects on incidence of cancer. The likelihood ratio test resulted in P = .0005, supporting robust association between the presence of a tau mutation and the development of cancer with HR = 3.72 (95% CI = 2.07–6.67), indicating a nearly fourfold risk of developing cancer in tau-mutated families.

“Patients carrying tau mutations are usually attended for neurodegeneration,” said Fabrizio Tagliavini, MD, Scientific Director at the IRCCS Foundation of the Carlo Besta Neurological Institutein Milan, Italy, and a co-author of this study, in a statement. “However, with further confirmation of our results, these patients could also be monitored for their risk of developing cancer. Clinicians should take into account both of these aspects of tau pathology.”

Giacomina Rossi, PhD, IRCCS Foundation of the Carlo Besta Neurological Institute in Milan, Italy, is the corresponding author of this study.

Funding for this study was provided by the Italian Ministry of Health, the Alzheimer’s Society (United Kingdom), the Medical Research Council (MRC, UK), and the MRC Programme. The study authors declared no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.