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Can Digestive Chemistry Uncover Sex-Specific Causes of Colon Cancer?

October 20, 2017

Women have a lower rate of colon cancer than men but higher rates of right-sided colon cancer, which affects the part of the colon nearer to the small intestine and is associated with worse outcomes than cancer of the left side, which is closer to the rectum.

Dr. Caroline Helen Johnson, Assistant Professor of Epidemiology, received this year’s Wendy U. and Thomas C. Naratil Pioneer Award and co-funding from the Yale Cancer Center to explore hormones and environmental factors related to metabolite production (such as sugars and amino acids) and beneficial bacteria that live in the colon as possible sources of this gender difference.

In the United States, colon and rectal cancer are together the number three cause of cancer death for women and the number two cause for men. This year, more than 50,000 people are expected to die of the disease.

“Colon cancer is the second most common cancer diagnosed among women worldwide,” Johnson said. “This work will benefit all women, particularly black women, who are at higher risk for colon cancer compared with other races or ethnic groups.”

It is clear that we need a greater understanding of the way hormones, cholesterol, and the metabolic action of bacteria in the colon react to form colon cancer differently in women and men.

Caroline Johnson

Bacteria in the colon produce organic molecules that help the body absorb cholesterol and fat-soluble vitamins. But in high concentrations, they can promote a toxic imbalance that leads to cancer.

The hormone estradiol regulates bile production and is thought to protect against colon cancer, as premenopausal women have higher levels of estradiol and lower levels of cholesterol than men of the same age. After menopause, cholesterol levels increase and exceed levels seen in similarly aged men while hormone therapy can provide a protective effect for women against the development of colon cancer.

“It is clear that we need a greater understanding of the way hormones, cholesterol, and the metabolic action of bacteria in the colon react to form colon cancer differently in women and men,” Johnson said.

Using metabolomics, state-of-the-art techniques to analyze the chemical fingerprints of the metabolic process used by bacteria in stored colon tissue of cancer patients, Johnson’s team will assess the relationship between the products of this process and the side of the colon that develops cancer. The researchers expect to find that women have a greater propensity for rightside colon cancer because of decreased estradiol following menopause.

Johnson said the study could reveal potential markers of colon cancer that could aid in early diagnosis and treatment. In addition, she anticipates the work will lead to targeted investigations of diet, the composition of beneficial bacteria in what’s known as the body’s microbiome, and lifestyle to determine causes of colon cancer and dietary recommendations that can help prevent the disease.

Women's Health Research at Yale's Pilot Project Program

  • Can a better understanding of the colon’s digestive chemistry uncover early signs and sex-specific causes of colon cancer to aid in prevention and treatment of this disease?
  • Can an affordable, rapid, noninvasive, and potentially self-administered test available to pregnant women prevent the spread of viral infections and preterm births?
  • Can a mobile phone app featuring an interactive character-based story help break the transgenerational cycle of intimate partner violence?

“When it comes to biology and behavior, women and men are not identical,” said Dr. Carolyn M. Mazure, Director of WHRY. “For the 20th year, WHRY is sparking innovation with studies designed to develop the best practices for detecting and treating diseases and conditions that may affect women and men differently.”

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Submitted by Carissa R Violante on October 20, 2017