Why Do Women with Mesothelioma Survive Longer than Men?

A recent study from Brigham and Women's Hospital in Boston has pinpointed for the first time gender-specific genetic mutations in mesothelioma patients that could lead to future treatment advances.

Women with mesothelioma typically have a survival advantage over men with the same disease, as numerous studies have currently shown.

But now, scientists are beginning to understand why that advantage exists, and how it could lead to more effective treatment for everyone.

"We were trying to identify genetic differences to help provide targets for specific therapies," Dr. Assunta De Rienzo, co-director of the Thoracic Surgery Laboratory at Brigham and Women's, told Asbestos.com. "If you can really understand why women do better, you can do something to help the men."

De Rienzo led the study titled "Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma." Dr. Raphael Bueno, chief of the thoracic surgery division at Brigham and Women, and Dr. David Sugarbaker, director of the Lung Institute at Baylor College of Medicine, also participated in the research.

As an instructor in surgery at Harvard Medical School, De Rienzo focused her research on the genetics and genomics of mesothelioma, using her background in molecular biology and cancer genetics.

Finding Molecular Pathways in Men and Women with Mesothelioma

"The idea is identifying specific groups of patients who will be helped by specific drugs," De Rienzo said. "You can try and do that at the molecular level."

Researchers examined the gene profile of mesothelioma tumors by gender through whole-genome sequencing, measuring those against normal tissue from the same patient to identify mutations.

They found different genetic mutations based upon mesothelioma subtypes and gender:

• There were twice as many mutations of the TP53 gene in female mesothelioma patients compared to male patients.



• Results showed much higher levels of the BAP1 gene expression among non-epithelioid tumors.



• The CDKN2A protein coding gene was mutated more frequently among men with non-epithelioid subtypes.

Their findings illustrated the mechanisms related to gender and histology drive mesothelioma.

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

Women with Mesothelioma Survive Longer than Men

The gender differences in molecular structure of the tumors are important because of the significant differences in mesothelioma survival between men and women.

Researchers from Mount Sinai Health System and Hofstra School of Medicine in New York analyzed the national Surveillance, Epidemiology and End Results (SEER) database and documented startling variations in survival time. Their review included 14,228 cases of mesothelioma - the largest gender-specific mesothelioma study conducted.

The five-year survival for women with mesothelioma was 13.4 percent, compared to just 4.5 percent for men. For those 50 or younger, the five-year survival for women was 38.6 percent, compared to just 17.3 percent for men.

Survival effects of gender, according to the study, differed upon treatment received, but it was consistent across most categories, including race, age and stage of disease. The percentage of women opting for surgery was higher.

Women have a much lower incidence rate of mesothelioma, primarily because they have less occupational exposure to asbestos, the primary cause of the disease. The condition is often associated with blue-collar professions, which historically employed men.

"For the first time, we have started seeing molecular differences between the men and the women," she said. "If we can get a better understanding of the genetic advantage women have, it will help everyone."