Scientific findings can help to recognize people at higher risk of developing this type of tumor and enable better treatment alternatives
After identifying more than 6 thousand genetic variations possibly associated with the emergence of head and neck cancer, researchers from the Cancer Genetics Laboratory (LAGECA) of the Faculty of Medical Sciences (FCM) at Unicamp investigated the role of the gene ERP29, involved in the processing of tumor proteins, in the development of this type of cancer.
The initial identification of these genetic variations, through large-scale genotyping with DNA microarrays, was part of the doctoral project of researcher Gustavo Jacob Lourenço, supervised by the professor of the Department of Anesthesiology, Oncology and Radiology at FCM, Carmen Silvia Passos Lima, and had the collaboration of the professor from the Department of Statistics of the Institute of Mathematics, Statistics and Scientific Computing (IMECC) at Unicamp, Benilton Carvalho.
The scientific findings – derived from master's research developed within the scope of the Postgraduate Program in Clinical Medicine – were recently published in the international journal Scientific Reports and may help to recognize people at higher risk of developing this type of tumor, in addition to enabling better treatment alternatives.
The research had 500 participants, including patients and a control group, and was guided by biologist Gustavo Jacob Lourenço and co-supervised by doctor Carmen Silvia Passos Lima.
Study data showed that individuals with the homozygous GG variant genotype had an increased risk of approximately 6 times for the occurrence of the tumor, given the instability of the gene's messenger RNA ERP29, which presents lower production of the ERp29 protein. And that patients with head and neck tumors carrying the GG genotype had worse survival than patients with other genotypes (AA or AG).
“Individuals with the GG genotype showed lower gene expression ERP29, lower production of the ERp29 protein and greater expression of miR-4421”, commented Juliana, explaining that the role of the ERp29 protein in tumor development and progression is still controversial. “In certain tumor types, such as breast and liver cancer, the gene ERP29 appears to facilitate tumor development. In lung cancer, it appears to inhibit tumor formation,” she said.
Still according to the LAGECA researcher, it is possible that individuals carrying the GG genotype have a higher risk of tumor occurrence and a worse prognosis due to lower expression of the ERP29, modulated by the microRNA called miR-4421. “The consequent loss of function as a tumor suppressor would facilitate cell proliferation and invasion,” stated Juliana.
Considered a public health problem, head and neck cancer has smoking and alcoholism among the main triggering factors, but the search for new markers, associated with the onset and prognosis of the disease, including genetic factors, has been a constant in the scientific community.
“Although we have described the role of the genetic variant in modulating the ERP29, the function of the ERp29 protein, as well as the mechanisms associated with the emergence and progression of head and neck cancer and the possible genes regulated by ERP29, remain unknown”, pondered Juliana, who is now continuing the project in her doctorate, seeking to evaluate the possible mechanisms modulated by the gene ERP29 and its relationship with the onset and progression of the disease.
Currently, many patients with head and neck cancer arrive at the hospital at an advanced stage of the disease. Treatment, in these cases, involves multimodal therapy with surgery, radiotherapy and cisplatin-based chemotherapy. Despite this, the survival rate for these patients is only 30% after five years.
“In the future, we hope to be able to offer individualized medical treatment to patients, with greater chances of a cure. In addition to offering additional recommendations to those at risk, genetic markers can help identify cases that require more aggressive treatment,” said the researcher.
original article published on the Unicamp FCM website.
