Obesity genes linked to uterine cancer
Endometrial cancer, or cancer of the uterine lining, is the most common gynecological malignancy. Obesity – defined as a body mass index (BMI) of 30 or higher – is a well-established risk factor for endometrial cancer, with obese women having a 4- to 6-times higher risk of the malignancy than nonobese women.
Ryan Delahanty, Ph.D., Xiao Ou Shu, M.D., Ph.D., and colleagues have evaluated the association between known obesity-related genetic variants and endometrial cancer risk in the Shanghai Endometrial Cancer Genetics Study. In the Nov. 15 American Journal of Epidemiology, the researchers report that obesity-associated variants in 22 of 26 genetic loci examined were present more often in women with endometrial cancer compared to control subjects. Nine of the obesity-linked variants – which represented seven genetic loci – were significantly associated with increased risk of the disease.
The results suggest that in addition to BMI, genetic markers of obesity may provide value in predicting endometrial cancer risk.
The research was supported by grants from the National Cancer Institute.
— Melissa Marino
Protein repairs esophageal DNA damage
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Alexander Zaika, Ph.D., and colleagues are examining the involvement of the p53 tumor suppressor family of proteins in repairing the DNA damage associated with gastric reflux.
In the December FASEB Journal, the researchers show that one member of this family, p73, plays the predominant role in repairing DNA damage induced by bile acid exposure. They found that the p73 protein regulates the expression of multiple DNA repair genes and that p73 deficiency in mice is associated with increased DNA damage. The results suggest that p73 may play a tumor suppressor role in the esophagus and could represent a target for therapies to combat esophageal cancer.
The research was supported by grants from the National Cancer Institute.
— Melissa Marino
Alcohol’s molecular mediators
Understanding how alcohol and drugs of abuse affect the brain’s neuronal connections is vital to developing treatments for alcohol and drug use disorders. Tiffany Wills, Ph.D., Danny Winder, Ph.D., and colleagues are probing alcohol’s effects in the BNST, a brain region involved in stress-induced relapse.
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The studies, reported in the Proceedings of the National Academy of Sciences, demonstrate that the GluN2B subunit plays a key role – and that NMDA receptor localization is important – in plasticity and alcohol-related effects in the BNST. Therefore, therapeutic agents with subunit and/or localization specificity may be effective in preventing relapse in patients with alcohol use disorders.
This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism and the National Institute of Mental Health.
— Leigh MacMillan
Pumping up the pancreas in pregnancy
During pregnancy, insulin-producing beta cells proliferate, or self-renew, to meet new metabolic demands. Pregnancy therefore represents a unique window for studying molecules involved in expanding beta cell mass, which could lead to novel therapies for patients with diabetes.
Patricia Labosky, Ph.D., and colleagues probed the role of the transcription factor Foxd3 – required for the maintenance and self-renewal of diverse progenitor cell types – in beta cell mass expansion during pregnancy. They report in the December issue of Endocrinology that mice carrying a pancreas-specific deletion of Foxd3 have impaired glucose tolerance and decreased beta cell mass, beta cell proliferation and beta cell size during pregnancy. They also show that several genes known to control proliferation are misregulated in islets isolated from the Foxd3 mutant mice.
The Foxd3 mutant mice provide a novel model for studying glucose intolerance (and gestational diabetes) during pregnancy and suggest that molecules such as Foxd3 may be useful for therapeutic applications involving expansion of existing beta cells.
This research was supported by grants from the Juvenile Diabetes Research Foundation, the National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases.
— Leigh MacMillan
We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.
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