Study reinforces value of colonoscopy screening for colorectal cancer prevention

BOSTON—A team of researchers, including those from Dana-Farber Cancer Institute, Brigham and Women's Hospital and the Harvard School of Public Health, will be reporting study findings that lend powerful scientific backing to the recommendation that people receive a colonoscopy screening to prevent colorectal cancer.

By analyzing medical data from nearly 90,000 people in two major health studies, the researchers found that participants who received either a colonoscopy or sigmoidoscopy exam – which allows doctors to look inside the large intestine through a thin tube and snip away precancerous growths – had a markedly lower rate of cancers in the rectum and lower (distal) colon than did other participants. The study, published in the Sept. 19 issue of the New England Journal of Medicine, showed, however, that only colonoscopy was associated with a lower rate of cancers in the upper (proximal) colon.

The study also helps answer the long-debated question over how frequently most people should have colonoscopies. The investigators found that patients who had a negative colonoscopy – in which no colorectal cancers or precancerous growths called adenomas were found – had a much lower risk of colorectal cancer for as long as ten years, reinforcing the standard recommendation that most people should have a colonoscopy every ten years beginning at age 50. When a colonoscopy did detect an adenoma, the lower risk lasted approximately five years.

"Large-scale clinical trials have shown that sigmoidoscopy reduces the overall incidence of colorectal cancer, and of deaths from the disease, although its effectiveness is greatest in the distal colon," says Shuji Ogino, MD, PhD, of Dana-Farber, Brigham and Women's Hospital, Harvard Medical School and Harvard School of Public Health, who co-led the study with Andrew Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School. "Although data from similar trials of colonoscopy are not yet available, the existing evidence suggests that it, too, is associated with lower rates of colorectal cancer. In the current study, we set out to measure how much protection sigmoidoscopy and colonoscopy provide and for how long, particularly for cancers originating in the proximal colon."

Approximately 150,000 Americans are diagnosed with colorectal cancer each year, and more than 50,000 die of it, according to American Cancer Society figures. Sigmoidoscopy, colonoscopy, and tests for hidden blood in the stool are the most common techniques of screening for the disease.

In sigmoidoscopy, a doctor uses a flexible tube with a camera at the tip to view the distal colon and rectum (the final portion of the large intestine). The procedure doesn't require patients to undergo a great deal of bowel preparation and usually doesn't involve sedation. Patients who receive sigmoidoscopy are generally advised to have one every five years. Colonoscopy also involves a flexible viewing tube, but one that's long enough to examine the entire colon and rectum. It is often performed with the patient sedated, and the recommended interval between exams is ten years for most people. Both procedures enable physicians to remove any polyps – small growths that can become cancerous – discovered during the exam.

In the new study, researchers used data from the Nurses' Health Study, which has tracked the health of 122,000 female nurses since 1976, and the Health Professionals Follow-up Study, which has followed 52,000 male health workers since 1986.

Among the 88,902 participants eligible for the study, 1,815 developed colorectal cancer during the 22 years of records examined. An analysis of the data showed that the colorectal cancer rate among those who had received endoscopies was just over half the rate for those who hadn't.

When researchers focused on different regions of the colorectum – distal or proximal – they found that colonoscopy lowered cancer-occurrence rates in both sections, albeit to a lower degree in the proximal section. Sigmoidoscopy, by contrast, lowered cancer-occurrence rates only in the distal section.

"We estimate that if all the participants in our study had undergone a colonoscopy, an additional 40 percent of colorectal cancer, including 61 percent of distal cancers and 22 percent of proximal cancers, would have been prevented," says the study's lead author, Reiko Nishihara, PhD, of Dana-Farber and the Harvard School of Public Health. "Moreover, both screening sigmoidoscopy and colonoscopy procedures were associated with a lower death rate from colorectal cancer, as compared with the rate for people who had neither procedure."

Among the participants whose colonoscopies turned up no polyps, colon cancer rates were sharply reduced for up to 15 years, lending strong support to the ten-year interval between exams recommended by the American Cancer Society and other bodies. (People who have an elevated risk of colorectal cancer – because of a family history of the disease or other bowel disease, or because precancerous adenomas were discovered during a previous exam – are usually advised to have more frequent colonoscopies.)

As part of the study, investigators also hoped to find pathological clues as to why colorectal cancers sometimes crop up in people who have recently undergone colonoscopies. It's thought that this occurs because of missed or incompletely removed polyps, or polyps that grow particularly fast due to abnormal genes.

The researchers identified 62 cancers that had been discovered within five years of a colonoscopy and that had been genetically analyzed. They found that these tumors were more likely to have certain abnormal "epigenetic" changes – alterations in the mechanism for switching genes on and off – than were tumors diagnosed at least five years after colonoscopy.

"Our findings suggest that while colonoscopy is an effective technique for preventing cancers of both the distal and proximal regions of the colorectum, sigmoidoscopy alone is probably insufficient for preventing cancers in the proximal area," Ogino says. "Our discovery of epigenetic changes in cancers diagnosed soon after colonoscopies should provide an important lead into what makes these cancers unique and how they may be more readily detected and removed."

Co-authors of the study are Paul Lochhead, MB, ChB, formerly of Dana-Farber and now at the University of Aberdeen, Scotland; Teppei Morikawa, MD; PhD, formerly of Dana-Farber and now at the University of Tokyo; Xiaoyun Liao, MD, PhD, Zhi Rong Qian, MD, PhD, Kentaro Inamura, MD, PhD, Sun A. Kim, MD, PhD, Mai Yamauchi, PhD, and Charles Fuchs, MD, of Dana-Farber and Brigham and Women's; Yu Imamura, MD, PhD, of Dana-Farber; Aya Kuchiba, PhD, of Dana-Farber and the Harvard School of Public Health; and Kana Wu, MD, PhD, Walter Willett, MD, DrPH, Edward Giovannucci, MD, ScD, MPH, and Bernard Rosner, PhD, MPH, of the Harvard School of Public Health.

The study was supported by grants from the National Institutes of Health NIH (P01 CA87969, P01 CA55075, 1UM1 CA167552, P50 CA127003, R01 CA151993, R01 CA137178, and K24 DK098311), The Bennett Family Fund, and the Entertainment Industry Foundation.

About Dana-Farber Cancer Institute

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center, designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Facebook: and on Twitter.

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