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The role of obesity in the development and progression of  breast cancer: Connecting epidemiology with molecular biolog

Dr. Paul Carroll, MD Student
Dr. Paul Carroll, MD Student

Obesity is an increasingly recognised risk factor for breast cancer. Adipocytokines produced by local mammary adipose tissue (paracrine) as well as distant adipose deposits (endocrine) may be the mechanism by which obesity influences breast cancer. The aims of this research project is to determine the effect of obesity on gene expression of the adipocytokines leptin (Ob) and adiponectin (Adipo) in mammary adipose tissue, and their receptors (ObR, AdipoR1/R2) in tumour tissue. Breast cancer patients (n=40) undergoing surgery had anthropomorphic (Tanita BIanalyser, Waist circumference,BMI) and serological measurements of obesity/metabolic status (Glucose,Lipids,Insulin) performed. Matched adipose and tumour tissue were analysed using quantitative real time PCR for mRNA expression of a panel of genes: Ob,Adipo,ObR,AdipoR1/R2. In mammary adipose tissue, there was upregulation of Ob in obese women (p<0.05) relative to normal weight controls. Tumour samples expressed all three receptors. Expression of ObR was significantly increased in obese women compared to normal weight cancer patients (p<0.05). Serum leptin tended to positively correlate with ObR expression (r=0.4, p=0.055) while serum insulin, a marker of obesity and insulin resistance correlated strongly with ObR (r=0.58, p<0.005).There was no difference in tumour AdipoR1/R2 or gene expression compared to obesity status. Obesity status is associated with increased expression of the leptin gene in mammary adipose tissue and with increased leptin receptor expression in tumour tissue. ObR is also positively correlated with serum leptin and insulin. This association suggests this adipocytokine pathway regulates tumour biology. This may link the molecular association of obesity with breast cancer, highlighting potential targets for prevention and treatment strategies.

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