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High BMI associated with increased risk for FASN-negative colorectal cancer
Kuchiba A. J Natl Cancer Inst. 2012;doi:10.1093/jnci/djr542.
Overweight and obese women were more likely to develop colorectal tumors with low or no fatty acid synthase expression, according to study findings, but there was no such association between high BMI and high or moderate fatty acid synthase expression.
Previous study results have shown that elevation of fatty acid synthase (FASN) is associated with poor prognosis.
Reviewing data collected on 109,051 women participating in the ongoing Nurses’ Health Study, researchers observed 1,351 colon and rectal cancers diagnosed from 1986 and 2004. Researchers then constructed tissue microarrays on the 536 available resected tumor samples and determined that 40% (n=217) were FASN-negative.
Age-adjusted incidence rate for FASN-positive colorectal cancers was 10.9/100,000 person-years and 7.1/100,000 person-years for FASN-negative cancers.
Women with a BMI of at least 25 had a statistically increased risk for FASN-negative colorectal cancer compared with women with a normal BMI of 18.5 to 22.9 (HR=1.78; 95% CI, 1.25-2.54). The association was even stronger for women with a BMI of at least 30 (HR=2.25; 95% CI, 1.49-3.40).
Neither women who were obese (HR=1.27; 95% CI, 0.88-1.83) nor those who were overweight (HR=1.23; 95% CI, 0.92-1.63) were at increased risk for FASN-positive tumors.
When researchers restricted their analysis to colon cancer, heavier women remained at increased risk for FASN-negative disease. Compared with women with normal BMI, the HR was 2.06 (95% CI, 1.29-3.27) for obese women and 1.65 (95% CI, 1.11-2.45) for overweight women.
Writing in an accompanying editorial, Dingzhi Wang, PhD, and Raymond N. DuBois, MD, PhD, both with The University of Texas MD Anderson Cancer Center, wrote that the results suggest that FASN accelerates tumor growth rather than drives cancer development. Further, these findings “indicate that the association of obesity with [colorectal cancer] may depend on cellular FASN status.”
“Increased de novo lipogenesis contributes to increased fat mass,” Wang and DuBois wrote. “The evidence that expression and/or activity of FASN is elevated in human breast, colorectal, prostate, endometrial, ovary and thyroid cancers supports the hypothesis that FASN responds to exacerbated de novo fatty acid biosynthesis in tumor cells, which is essential for generating cell membranes during tumor cell proliferation.”
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