TP53 Mutations Associated with Decreased Survival in Head and Neck Cancer
According to an article recently published in the New England Journal of Medicine, mutations in the TP53 gene result in lower survival rates for patients diagnosed with squamous-cell carcinoma of the head and neck. Patients with this genetic mutation may benefit from certain therapeutic approaches.
Head and neck cancers originate in the oral cavity (lip, mouth, tongue), salivary glands, paranasal sinuses, nasal cavity, pharynx (upper back part of the throat), larynx (voice box), and lymph nodes in the upper part of the neck. Worldwide, head and neck cancer is diagnosed in approximately 640,000 people annually and is responsible for approximately 350,000 deaths each year.
Squamous cell carcinoma of the head and neck is the most common type of head and neck cancer; it originates in squamous cells.
As more is understood about cancer, genetics has been recognized as a crucial factor in the disease’s development. One area of genetic research involves the p53 protein, which is produced by the TP53 gene. The p53 protein suppresses the abnormal growth of cancer cells. If mutations exist in the TP53 gene, abnormal p53 proteins are produced that often lack the ability to suppress the growth of tumors.
Researchers from the United States and Italy recently conducted a clinical trial to evaluate the potential effects of a mutated TP53 gene on outcomes among patients with squamous-cell carcinoma of the head and neck. This trial included 560 patients who underwent surgery in an attempt to cure their disease. Mutations of the TP53 gene were analyzed from samples of the cancer taken during surgery. Mutations were classified as either disruptive or nondisruptive, depending upon how the TP53 mutation affected the p53 protein. Patients were followed for approximately seven years.
- TP53 mutations were found in over 53% of patients.
- Overall, any type of mutation within the TP53 gene was associated with a 40% decrease in overall survival.
- Patients who had TP53 mutations classified as disruptive mutations were associated with a 70% decrease in overall survival compared with patients with no TP53 mutations.
The researchers concluded that mutations within the TP53 gene, particularly those that are classified as disruptive mutations, significantly decrease overall survival among patients with squamous-cell head and neck cancer. Future trials will undoubtedly continue to explore genetics’ role in cancer with the goal of individualizing therapy.
Reference: Poeta M, Manola J, Goldwasser M, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. The New England Journal of Medicine. 2007;357:2552-2561.