An international coalition of cancer specialists led by a researcher now at Baylor College of Medicine has identified an immune related gene called transforming growth factor beta receptor 1 (TGFBR1) that appears to play an important role in determining whether a person develops a cancer related to human papilloma virus (HPV). HPV is, in particular, associated with anal cancer and cancers of the cervix, and the head and neck.
Their findings appear in the journal Cancer Research.
Until recently, head and neck cancer has been found primarily in smokers, but there has been a rise in HPV-associated head and neck cancer in nonsmokers. The head and neck cancer most-associated with HPV is oropharyngeal cancer, involving the tonsils and base of the tongue.
HPV is also one of the most common sexually transmitted diseases, with certain strains known to cause head and neck and/or cervical cancer.
The National Cancer Institute predicts that HPV-positive oropharyngeal cancer will likely surpass cervical cancer as the most common HPV-associated cancer in the United States by 2020.
“The real mystery is that in western countries, pretty much everyone is exposed to HPV but only a small number of people get HPV-related cancers,” said Dr. Andrew Sikora, vice-chair for research in the Department of Otolaryngology Head and Neck Surgery at Baylor. “We are trying to figure out what makes the people who actually get the cancer different from those who don’t, given that so many people are exposed.”
Using data collected as part of a genome-wide association study of head and neck cancer performed by the INHANCE consortium, the researchers were able to associate alterations in a number of immune-related genes with oropharyngeal cancer. One of these genes, TGFBR1, was found to be deregulated in patients with both oropharyngeal and cervical cancer.
“The fact that we were able to independently replicate our findings in two-different HPV-related cancers is exciting because it suggests that we have found something that is critical to the biology of how HPV causes cancer,” said Sikora, also co-director of the head and neck cancer program in the NCI-designated Dan L Duncan Cancer Center Baylor.
“We hope to learn more about this gene and how it affects cancer,” Sikora added. “In the future we hope to develop a tool to identify who is more susceptible to HPV-related cancers.”
Sikora conducted the study while on faculty at the Icahn School of Medicine at Mount Sinai in New York prior to joining the Baylor faculty in July 2014. Co-author, Paolo Boffetta, director of the Institute for Translational Epidemiology at ISMMS was one of the investigators for the original INHANCE study.
Others who took part in this study include: Chaya Levovitz; John Finnigan; Sara Alshawish; Marshal R. Posner; Weijia Zhang; Eric E. Schadt; Eric M. Genden and Paolo Boffetta; The Icahn School of Medicine at Mount Sinai in New York; Dan Chen and Emma Ivansson of Uppsala University, Uppsala, Sweden.
Funding for this work comes from NIH National Cancer Institute (1F30CA165615-01) (CL); National Institute of Dental and Craniofacial Research (5R03DE021741-02) (AGS); NIH National Cancer Institute (1K08CA154963-01A1) (AGS).