MedWire News: US study results indicate that the poor outcomes often experienced by overweight men with prostate cancer may be mediated by the fatty acid synthase (FASN ) gene.
The findings suggest that FASN interacts with body mass index (BMI) in such a way that it increases the risk for advanced prostate cancer, and that inhibition of FASN may reduce prostate cancer mortality, particularly among overweight men.
"We found that among four of the five common tagging single nucleotide polymorphisms (SNPs) in the FASN gene, there were several associations with prostate cancer risk, BMI, FASN overexpression, and prostate cancer death," report Jing Ma, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues.
The team examined whether inherited variation in the FASN gene or variations in tumor FASN expression correlated with prostate cancer mortality, and whether these effects differed according to BMI.
The researchers genotyped 1331 men with prostate cancer and 1267 healthy age-matched controls for five SNPs within FASN .
The most significant associations were observed among carriers of the homozygous AA (vs GG) variant of rs1127678, who had a 2% higher pre-diagnosis BMI.
Among overweight (BMI ≥25 kg/m2) prostate cancer patients who died, the median BMI was significantly higher for those with the AA variant of rs1127678 than those with the GG wild type variant of the SNP, at 28.8 kg/m2 versus 26.7 kg/m2.
Furthermore, the relative risks for advanced prostate cancer and prostate cancer mortality in overweight men with the AA variant were 2.49 and 2.04 times higher than for normal weight men with the wild type GG variant.
Ma and team also report a significantly increased risk for lethal prostate cancer among overweight men with high tumor FASN expression (top two tertiles of expression). Compared with having low tumor expression (bottom tertile), men with high tumor FASN expression were 2.73 times more likely to develop lethal prostate cancer.
"Although no single SNP was related to all of the outcomes, our current data and prior literature suggest that there may be multiple biologic pathways in which FASN polymorphisms may be influencing prostate cancer outcomes," write Ma et al in the Journal of Clinical Oncology.
They hypothesize that, in the "metabolically permissive environment" of a higher BMI, FASN may be better able to influence tumorigenesis or tumor maintenance than it can at lower body weights.
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