Sulfur Microbial Diet Linked to Precursor of Early-onset Colorectal Cancer

In contrast to the sharp declines in colorectal cancer (CRC) among U.S. adults ages 50 years and older, there is an alarming rise in early-onset CRC, which is typically characterized by more aggressive tumors.

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Massachusetts General Hospital researchers previously reported that among older men, long-term adherence to the "sulfur microbial diet" was associated with an increased risk of CRC. Microbial metabolism of dietary sulfur produces hydrogen sulfide, a gastrointestinal carcinogen. The sulfur microbial diet is high in processed meat, liquor and low-calorie drinks, and low in beer, fruit juice, legumes, vegetables and sweets/desserts.

Now, the team has extended its findings. In a paper in Gastroenterology, Long H. Nguyen, MD, assistant professor in the Division of Gastroenterology at Mass General, Andrew T. Chan, MD, MPH, director of Cancer Epidemiology in the Mass General Cancer Center, chief of the Clinical and Translational Epidemiology Unit in the Department of Medicine and vice chief for Clinical Research in the Division of Gastroenterology, and colleagues link the sulfur microbial diet to increased risk of early-onset conventional adenoma, a surrogate endpoint for CRC, in young women.

Methods

The researchers analyzed data from the Nurses' Health Study II, a prospective longitudinal study of 116,429 female registered nurses who were 25 to 42 years old at enrollment in 1989. The analysis included 30,818 women who underwent at least one lower endoscopy between 1991 and 2015 and were <50 years old at the time.

Every four years from 1991 through 2011, participants reported their dietary intake on a semiquantitative food frequency questionnaire and were scored according to their adherence to the sulfur microbial diet. In 1998, they were asked to recall their diet between 1960 and 1982, when they were typically 13 to 18 years old.

Adult Diet

After adjustment for putative CRC risk factors, the likelihood of early-onset conventional adenoma was:

• Significantly higher for women in the highest quartile (Q4) of sulfur microbial diet scores compared with women in the lowest quartile (Q1) (OR, 1.31; P_trend=0.02)
• Largely driven by neoplasia in the proximal colon (OR Q4 vs. Q1, 1.58; P_trend=0.01)
• Particularly elevated for lesions with greater malignant potential (tubulovillous or villous histology, OR Q4 vs. Q1, 1.65; P_trend=0.04) versus tubular adenomas (OR Q4 vs. Q1, 1.24; P_trend=0.09)

No association was detected between the sulfur microbial diet and adenomas diagnosed after age 50.

Adolescent Diet

For high school sulfur microbial diet scores above the median versus those below:

• Overall risk of conventional adenomas—OR, 1.13 (P_trend=0.03)
• Risk of polyps of advanced histology—OR, 1.27 (P_trend=0.17)
• Risk of polyps in the proximal colon—OR, 1.26 (P_trend=0.47)

Looking Ahead

Early identification of adults at high risk of colorectal adenoma is a critical unmet need, and dietary assessment may prove to be important in this regard.

It will also be essential to establish how other determinants of gut microbes (e.g., physical activity and medications) influence the link between diet and carcinogenic microbes and whether dietary modification can change the long-term carriage of harmful gut bacteria and ultimately prevent disease.

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