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Gender differences in energy for growth for CRC tumour cells

Tue, 03/17/2020 - 17:22
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A study led by researchers at Yale University have found that colon cancer tumour cells produce energy for growth differently in women and men, and that this difference is associated with a more aggressive form of tumour growth with a higher incidence in women. The study, ‘Sex Differences in Colon Cancer Metabolism Reveal A Novel Subphenotype’, published in Scientific Reports, is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with right-sided colon cancer, with implications for tumour progression and outcomes in colorectal cancer patients (CRC) patients.

"With this new information and many promising leads, our work is helping to determine what can be done to prevent worse outcomes for women who develop this deadlier form of colon cancer," said Dr Caroline Johnson, assistant professor of Epidemiology at Yale School of Public Health, and co-senior author of the study. "This work will benefit all women, but particularly black women, who are at higher risk for colon cancer compared with other races or ethnic groups."

Women have a lower rate of colon cancer than men but a higher prevalence of right-sided colon cancer, a deadlier form of the cancer that is associated with a 20% increased risk of death compared with cancer of the left side.

With initial funding from Women's Health Research at Yale, the Yale Cancer Center and the National Institutes of Health, the study found clues to the underlying mechanisms driving this difference in colon cancer risk. Employing new techniques collectively called "metabolomics," the researchers investigated the molecular products of digestion and cellular processes created by the foods people consume, their hormone production, and the specific bacteria residing inside the colon. Examining normal colon and tumour tissue samples from women and men with colon cancer, the researchers analysed concentrations and interactions of metabolites, the small chemicals such as sugars and amino acids which are transformed during metabolism.

They found that women with right-sided colon cancer have increased levels of metabolites known as fatty acids, which undergo a process known as fatty acid oxidation to produce energy. They also have increased levels of glutamine and asparagine, amino acids which have been linked to more aggressive tumour growth. In contrast, men with colon cancer have increased levels of metabolites such as lactate, which produce energy through a different pathway.

"These results indicate that colon cancer tumours grow differently in women and men and thus may require different approaches to stop their growth," added Johnson.

In addition, the researchers examined clinical outcomes of patients, and found lower survival rates for women with colon cancer whose tumours showed a sex-specific molecular pathway for cellular energy production.

Johnson, in collaboration with co-senior author, Dr Sajid Khan, associate professor of surgery, aim to eventually identify a biological indicator to serve as a warning for the development of the deadlier right-sided colon cancer, which is more difficult to identify at early stages compared with left-sided colon cancer.

To access this paper, please click here