New Link Between Women with Mesothelioma and Survival Genes

Men with mesothelioma outnumber women four to one. However, numerous studies have shown that women with mesothelioma often have a survival advantage over men. Now, scientists might have a better understanding of why.

Researchers have identified a gene that predicts the prognosis and treatment outcome for women with malignant pleural mesothelioma. The research took place as part of the International Mesothelioma Program at Brigham and Women’s Hospital in Boston.

Dr. Assunta De Rienzo led the new study after years of research highlighting the sex-based disparity among mesothelioma patients.

“The goal is finding specific therapies according to the molecular characteristics of the tumor,” De Rienzo said. “This will help apply personalized medicine for mesothelioma patients.”

The RERG gene, which stands for RAS-like estrogen-regulated growth inhibitor, may be the key to understanding why women consistently live longer than men following mesothelioma surgery.

Researchers pointed to low RERG expression in women as a significant predictor for an increased risk of death. In other words, high levels of the RERG gene correlate directly with improved prognosis and survival advantage in women.

Estrogen-Signaling Genes Could Explain Survival Differences

This recent study aimed to determine whether estrogen-signaling genes such as RERG could predict survival in mesothelioma patients.

At Brigham and Women’s Hospital, scientists validated the research by balancing the numbers of men and women who participated. They also controlled for other variables that could alter a patient’s prognosis.

Estrogen is an essential hormone in human health, and studies have explored its impact on other sex-based cancers. Besides regulating reproductive processes, estrogen aids in developing the cardiovascular, bone, nervous and immune systems.

Previous studies have identified estrogen receptor beta levels in tumors as another indicator of survival among patients with malignant pleural mesothelioma.

Identifying additional estrogen-signaling genes could lead to therapeutic advancements for patients undergoing chemotherapy for mesothelioma or other treatments.

In this new study, researchers classified the RERG gene as a female-specific biomarker that predicted mesothelioma prognosis. In breast cancer, high RERG protein correlates with longer intervals of disease-specific survival without metastasis.

The results revealed that women with high RERG expression had a median overall survival of 33.1 months compared to 15.9 months for women with low RERG expression.

Researchers at Brigham and Women’s emphasized that the mechanism of mesothelioma tumor control by the RERG gene is still unknown and requires further investigation.

“Surprisingly, despite demonstrating a statistically significant, sex-specific relationship between RERG expression and overall survival, no evidence of estrogen receptor expression was found at either the RNA or protein level in MPM tumor tissues,” the authors stated.

The researchers further specified that “no association between circulating estradiol levels and survival was observed.” They also reported that “survival in men was not associated with RERG expression,” meaning that the RERG gene was not a predictor of prognosis for men with malignant pleural mesothelioma.

Women Living Longer Despite Mesothelioma Treatment Differences

In a study from May 2020, researchers concluded women had an average overall survival of 20.8 months compared to 15.8 months for men.

Experts have attributed this survival advantage to several factors. Women often develop mesothelioma at a younger age, typical with secondary asbestos exposure outside of occupational hazards. Diagnosis at a younger age usually means fewer comorbidities at the time of diagnosis.

Women also typically present with epithelioid histology, which responds better to treatment. Younger age and overall better health allow women to be eligible for more aggressive mesothelioma therapies.

However, research from June 2020 published in the journal Clinical Lung Cancer illustrated that women were 15% less likely to receive aggressive mesothelioma surgery. Many mesothelioma specialists agree surgery often provides the best chance at survival after diagnosis.

The study included data from more than 18,000 patients in the National Cancer Database and found that women were 20% less likely than men to receive mesothelioma chemotherapy.

It’s unclear why women aren’t gaining the same access to aggressive mesothelioma treatments as men, but experts suggest it’s due to the historically male-dominated focus on occupational asbestos exposure.

With a natural survival advantage now clear after results from research on the RERG gene, women have the potential for significantly better outcomes after aggressive mesothelioma therapy.

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