Rutgers Cancer Institute Scientist Awarded $3.5 Million Grant to Explore if Gut Bacteria Influences Breast Cancer

Rutgers cancer epidemiologist Tengteng Wang will test whether specific bacteria in stool samples of healthy women predict subsequent cancer development in hopes of ultimately finding ways to prevent the disease.

"Genetic risk cannot be changed. The microbiome can," said Wang, a member of the Cancer Prevention and Control Program at the Rutgers Cancer Institute, New Jersey's only National Cancer Institute-designated Comprehensive Cancer Center, together with RWJBarnabas Health. "If we can find and understand the specific microbiota or microbial metabolites that matter, we have a target for prevention."

Study funding comes from a highly selective National Cancer Institute R37 MERIT Award for outstanding researchers early in their careers. It guarantees $3.5 million over 5 years, but strong early progress can secure an additional $1 million over 2 more years.

Study data will come from the Nurses' Health Study II, a prospective cohort study that has tracked health-related data from more than 116,000 initially healthy female nurses for more than 35 years, repeatedly collecting information about each woman's diet, lifestyle, reproductive factors, medical history, and health outcomes.

Between 2019 and 2023, more than 18,000 cancer-free postmenopausal participants provided stool samples for preservation. More than 300 of those women have since been diagnosed with breast cancer. Wang expects the number to reach 500 by 2029.

Wang and her collaborators at Brigham and Women's Hospital, the Harvard T.H. Chan School of Public Health, and the Broad Institute will compare samples from the 300 women who developed breast cancer after giving samples with those from 300 who did not. They will sequence the microbial DNA in each sample and measure the chemicals the microbes produce, which show what the bacteria are doing rather than only which species are present.

For study participants who gave both stool and blood samples, the team will test whether specific microbial features track with measured levels of estrogen, testosterone and inflammatory proteins.

If researchers find that specific bacteria seem to be driving cancer development, Wang and her team will use additional data from the study to examine how lifestyle can affect concentrations of the suspect bacteria.

The Nurses' Health Study II also provides decades of data on what the women ate and how they lived. Using about 8,000 participants whose microbial DNA has already been sequenced, the team will examine whether dietary fiber, coffee, alcohol, fruit and vegetable intake, reproductive history, weight gain and night-shift work affect bacteria linked to risk and whether exposures in early adulthood, in recent years or accumulated over a lifetime matter most.

Gut bacteria are a plausible cause of at least some breast cancers because some bacteria can reactivate estrogen that the body has already processed for elimination and return it to circulation. Others produce compounds that affect inflammation and immune activity.

However, previous human research on gut bacteria and breast cancer has compared diagnosed patients with healthy women and thus been unable to determine whether differences arose before or after the cancer formed.

"Most of what we know connects the microbiome to cancer treatment or to colorectal cancer," said Wang, who is also an assistant professor at Rutgers Robert Wood Johnson Medical School. "If we can identify microbial features that contribute to risk, and understand what shapes them, we may eventually be able to develop microbiome-targeted preventive strategies for women at increased risk."