Lung Cancer in women who have never smoked is the focus of the study proposed by Dr. Alice Berger, a translational researcher at Fred Hutchinson Cancer Research Center which was chosen to receive the 2017 LCFA/IASLC Lori Monroe Scholarship for Translational Lung Cancer Research.
She will use the scholarship to perform genome sequencing on lung tumors found in women with no history of smoking who participated in the Women’s Health Initiative (WHI). The WHI, coordinated by Fred Hutchinson Cancer in Seattle, WA, is one of the largest U.S. prevention studies of its kind, involving more than 161,000 women.
Berger will conduct the research in collaboration with Dr. Garnet Anderson, principal investigator of the WHI Clinical Coordinating Center, senior vice president and director of the Public Health Sciences Division and Fred Hutch 40th Anniversary Endowed Chair.
According to Berger, previous genetic studies of lung cancer have focused mainly on tumors from people with a history of smoking; the largest study of never-smokers to date has included only 33 participants.
“In the small number of tumors from never-smokers who have been profiled, we can see that the genetic changes in never-smokers are very different from that of smokers,” said Berger, a researcher in the Hutch’s Human Biology and Public Health Sciences divisions.
“The goal of this project is to identify new potential drug targets in lung cancer and to better understand the etiology of lung cancer in patients without a smoking history,” she said.
Dr. Berger’s hope is to find more “targets” for additional personalized treatments for lung cancer. Find out more on personalized medicine for lung cancer. And, download LCFA’s Personalized Medicine Brochure.
The proportion of lung cancers that occur in people that have never smoked is increasing. Women
are particularly affected; In 2016, 24% of lung cancer cases in women were diagnosed in ‘never-
smokers,’ individuals that have smoked less than 100 cigarettes in their lifetime. Despite the
prevalence of lung cancer in never-smokers, previous genome sequencing studies of lung
cancers have predominantly analyzed tumors from smokers, yet it is these studies that have
discovered the most clinically important targets in lung cancer such as EGFR mutations and ALK
fusion genes. Genome studies of never-smokers have typically focused only these already known
genetic alterations, so we are completely blind to other genetic events that might contribute to
disease in never-smokers. The goal of this work is to apply unbiased, genome-wide sequencing
to identify genetic alterations in lung cancers from never-smokers. The project is the launch of a
unique collaboration between my lab and the Women’s Health Initiative. The Women’s Health
Initiative has led a decades-spanning study involving over 160,000 post-menopausal women. An
overview of our study is shown in the figure below.
In the past year, we have met a number of critical milestones on our way to completing the project.
First, we secured institutional review board (IRB) approval to work with these human specimens
and approval from the National Heart, Lung, and Blood Institute (NHLBI) steering committee that
oversees the Women’s Health Initiative. Second, we have received tissue from 106 of the 130
participants requested for this study. Third, all tissue has undergone molecular review and
imaging in the laboratory of Dr. Peggy Porter (Fred Hutchinson Cancer Research Center). 99/106
of these cases had sufficient material for DNA extraction. DNA from the first 19 individuals was
sent to the Dana-Farber Center for Cancer Genome Discovery in January, and initial sequencing
data is expected back imminently. Another 77 samples have been sent for sectioning and DNA
extraction and are expected to be sent for sequencing in the next 4-6 weeks.
Last, an exciting outcome of our funding support from the LCFA/IASLC has been our ability to
secure additional funding to complete the sequencing proposed in this study. We were recently
funded by the Prevent Cancer Foundation ($100,000) to sequence additional samples and focus
on understanding the underlying environmental causes that might contribute to lung cancer in
these individuals. We also secured an additional $100,000 from the Seattle Translational Tumor
Research program to perform sequencing of samples at Fred Hutch and contribute our data to a
new genomics repository aimed at managing the data privacy and sharing with the most current
technologies and permissions. We are very grateful for the support and vision of the LCFA/IASLC
in enabling us to launch this project and the catalytic effect the support has had on our project