Nav: Home

Genetic variants are associated with susceptibility to mouth and throat cancer

December 15, 2016

A number of genetic variants associated with susceptibility to oral cavity and pharyngeal cancer have been described in an international study published in the journal Nature Genetics.

The most noteworthy finding was an association between cancer of the oropharynx and certain polymorphisms (alternative versions of a given DNA sequence) found in the human leukocyte antigen (HLA) genomic region. HLAs, proteins found on the surface of most cells in the body, play an important role in recognizing potential threats and triggering the immune response to foreign substances.

According to Eloiza Helena Tajara, a professor at the São José do Rio Preto Medical School (FAMERP) in São Paulo State, Brazil, and co-author of the article, a specific group of variants in this region, located on chromosome 6, is associated with enhanced protection against oropharyngeal cancer caused by human papilloma virus (HPV).

"Previous research showed that these same variants confer protection against cancer of the uterine cervix, which is known to be associated with HPV," Tajara said. "Our findings suggest that the genes that control the immune system play a key role in predisposition to HPV-related tumors. This discovery points to the possibility of clarifying the mechanisms whereby such tumors develop and of designing methods for monitoring risk groups."

The study was coordinated by the International Agency for Research on Cancer (IARC) and involved 40 research groups in Europe, the United States, and South America. The Brazilian participants are members of the Head & Neck Genome Project (GENCAPO), a consortium of scientists affiliated with several institutions.

In a recent study, GENCAPO evaluated more than 7 million genetic variants in samples from 6,034 patients with head and neck cancer. The cases comprised 2,990 oral cavity tumors, 2,641 oropharyngeal tumors, 305 tumors in the hypopharynx (the bottom part of the pharynx near the esophagus), and 168 tumors in other regions or more than one region concurrently. The study population also included samples from 6,585 people without cancer as controls.

The researchers detected eight loci (genomic sites) associated with susceptibility to these types of tumor. Seven had not previously been linked to mouth or throat cancer.

According to Tajara, the IARC set out to focus on analyzing oral cavity and oropharynx tumors because there are no genome-wide association studies of these two tumor types. Although these cancers are predominantly caused by tobacco and alcohol use, the importance of HPV, particularly HPV16, as a cause of oropharyngeal cancer has become more evident in recent years.

"The throat is the most affected area among head and neck cancer subsites, likely because its tissue is more receptive to the virus," Tajara said.

In the article, the researchers note that the proportion of HPV-related oropharyngeal cancer cases is estimated to be approximately 60% in the US and 30% in Europe but lower in South America.

"One finding that was expected to some extent was the absence of HLA associations with oropharyngeal cancer, which may be due to the fact that the frequency of HPV-positive oropharyngeal cancer is less than 10% in South America," Tajara said. "The same factor appears to account for the weak association between the variants identified and HPV-positive oral cavity cancer, which is also far less frequent than HPV-negative oral cavity cancer."

In her view, the strong rise in cases linked to HPV in the US could be partly due to a change in sexual habits, especially regarding the practice of oral sex. "It's possible that Brazil is still in a transition stage and that the habits that favor infection are only starting to become more common. If so, the effects will appear in a few years' time," she said.

Previous studies have already shown that HPV-associated head and neck cancers affect younger people and develop rapidly. By contrast, cases associated with tobacco and alcohol use as well as poor oral hygiene are more prevalent in those over fifty years old and progress more slowly but are harder to treat.

In addition to DNA in tissue samples taken from participants of the study, data were also collected on environmental and clinical factors possibly associated with the development of this type of cancer, such as smoking, alcohol consumption, and age.

According to Tajara, thanks to the joint efforts of 40 research groups it was possible to obtain data on a significant number of patients, thus enhancing the impact and reliability of the results. The GENCAPO team contributed some 1,000 samples from tumors for analysis.

"Based on these results, we can try to understand from the molecular standpoint how the observed polymorphisms interfere with the response to HPV infection," Tajara said. "This may give us clues as to how to protect people and how to reduce the incidence of this type of tumor."
-end-


Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.