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Study tightens connection between intestinal microorganisms, diet, and colorectal cancer

January 26, 2017

BOSTON -- A new study provides some of the strongest evidence to date that microorganisms living in the large intestine can serve as a link between diet and certain types of colorectal cancer, the lead authors at Dana-Farber Cancer Institute and Massachusetts General Hospital report.

The paper, published online today by JAMA Oncology, focuses on Fusobacterium nucleatum, one of hundreds of types of bacteria that dwell in humans' large intestines, and one that is thought to play a role in colorectal cancer. By tracking the diets of more than 137,000 people for decades and examining more than 1,000 colorectal tumor samples for F. nucleatum, the researchers determined that individuals with a "prudent" diet -- rich in whole grains and fiber -- had a lower risk of developing colorectal cancer containing the bacterium, but their risk for colorectal cancer that lacked the bacterium was essentially unchanged.

Prudent diets appear to protect against colorectal cancer. The new study suggests that healthy foods may achieve these benefits, in part, by altering the relative amounts of various microorganisms in the digestive tract, including F. nucleatum.

"Though our research dealt with only one type of bacteria, it points to a much broader phenomenon -- that intestinal bacteria can act in concert with diet to reduce or increase the risk of certain types of colorectal cancer," said Shuji Ogino, MD, PhD, of Dana-Farber, Harvard T.H. Chan School of Public Health, and Brigham and Women's Hospital, the co-senior author of the study with Charles Fuchs, MD, MPH, director of the Gastrointestinal Cancer Center at Dana-Farber and Brigham and Women's, and Andrew Chan, MD, MPH, of Massachusetts General Hospital, Brigham and Women's, and the Broad Institute of MIT and Harvard.

"These data are among the first in humans that show a connection between long-term dietary intake and the bacteria in tumor tissue. This supports earlier studies that show some gut bacteria can directly cause the development of cancers in animals," added Chan.

The research drew on dietary records of 137,217 participants in the Nurses' Health Study and Health Professionals Follow-up Study -- large-scale health-tracking studies - -some of whom developed colon or rectal cancer over a period of decades. The researchers measured the levels of F. nucleatum in the patients' tumor tissue and blended these data with information of diet and cancer incidence.

"Recent experiments have suggested that F. nucleatum may contribute to the development of colorectal cancer by interfering with the immune system and activating growth pathways in colon cells," Ogino remarked. "One study showed that F. nucleatum in the stool increased markedly after participants switched from a prudent to a Western-style, low fiber diet. We theorized that the link between a prudent diet and reduced colorectal cancer risk would be more evident for tumors enriched with F. nucleatum than for those without it."

That is precisely what the study results showed: Participants who followed a prudent diet had a sharply lower risk of developing colorectal cancer laden with F. nucleatum. But they received no extra protection against colorectal cancers that didn't contain the bacteria.

"Our findings offer compelling evidence of the ability of diet to influence the risk of developing certain types of colorectal cancer by affecting the bacteria within the digestive tract," Ogino commented.

"The results of this study underscore the need for additional studies that explore the complex interrelationship between what someone eats, the microorganisms in their gut, and the development of cancer," said Chan.
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The lead authors of the paper are Raaj Mehta, MD, of Mass General, Yin Cao, ScD, of Mass General and Harvard T.H. Chan School of Public Health, and Reiko Nishihara, PhD, of Dana-Farber, Brigham and Women's, the Broad Institute, and Harvard T.H. Chan School of Public Health. Co-authors are Kosuke Mima, MD, PhD, Zhi Rong Qian, MD, PhD, Keisuke Kosumi, MD, PhD, Tsuyoshi Hamada, MD, PhD, Yohei Masugi, MD, PhD, Susan Bullman, PhD, and Jeffrey Meyerhardt, MD, MPH, of Dana-Farber; Wendy Garrett, MD, PhD, of Dana-Farber, the Broad Institute, and Harvard T.H. Chan School of Public Health; David Drew, PhD, of Mass General; Mingyang Song, MD, ScD, of Mass General and Harvard T.H. Chan School of Public Health; Jonathan Nowak, MD, PhD, and Xuehong Zhang, MD, ScD, of Brigham and Women's; Aleksandar D. Kostic, PhD, of the Broad Institute; Kana Wu, MD, PhD, and Curtis Huttenhower, PhD, of Harvard T.H. Chan School of Public Health; Teresa T. Fung, ScD, RDN, of Simmons College; Walter Willett, MD, DrPH, and Edward Giovannucci, MD, ScD, of Harvard T.H. Chan School of Public Health and Brigham and Women's.

This work was supported by U.S. National Institutes of Health (grants P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA137178, K24 DK098311, R01 CA202704, R01 CA151993, R35 CA197735, and K07 CA190673); and by grants from The Project P Fund for Colorectal Cancer Research, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance.

About Dana-Farber Cancer Institute

From achieving the first remissions in childhood cancer with chemotherapy in 1948, to developing the very latest new therapies, Dana-Farber Cancer Institute is one of the world's leading centers of cancer research and treatment. It is the only center ranked in the top 4 of U.S. News and World Report's Best Hospitals for both adult and pediatric cancer care.

Dana-Farber sits at the center of a wide range of collaborative efforts to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber/Brigham and Women's Cancer Center provides the latest in cancer care for adults; Dana-Farber/Boston Children's Cancer and Blood Disorders Center for children. The Dana-Farber/Harvard Cancer Center unites the cancer research efforts of five Harvard academic medical centers and two graduate schools, while Dana-Farber Community Cancer Care provides high quality cancer treatment in communities outside Boston's Longwood Medical Area.

Dana-Farber is dedicated to a unique, 50/50 balance between cancer research and care, and much of the Institute's work is dedicated to translating the results of its discovery into new treatments for patients locally and around the world.

About Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."

Dana-Farber Cancer Institute

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