Body mass index and risk of colorectal cancer according to fatty acid synthase expression in the nurses' health study.
Fatty acid synthase (FASN) plays an important role in energy metabolism of fatty acids and is overexpressed in some colon cancers. We investigated whether associations between body mass index (BMI) and risk of colorectal cancer varied according to FASN expression. During follow-up of 109,051 women in the ongoing prospective Nurses' Health Study, a total of 1351 incident colon and rectal cancers were diagnosed between 1986 and 2004. We constructed tissue microarrays of the available resected tumor samples (n = 536), and FASN expression was analyzed by immunohistochemistry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. All statistical tests were two-sided. High BMI was associated with an increased risk of FASN-negative (no or weak expression) colorectal cancer compared with normal BMI (high BMI [≥ 30 kg/m(2)], ie, obese vs normal BMI [18.5-22.9 kg/m(2)], HR = 2.25, 95% CI = 1.49 to 3.40, P(trend) < .001) but not with FASN-positive (moderate to strong expression) colorectal cancer. A statistically significant heterogeneity in colorectal cancer risks was observed between FASN-negative and FASN-positive tumors (P(heterogeneity) = .033). The age-adjusted incidence rates for FASN-positive and FASN-negative colorectal cancers were 10.9 and 7.1, respectively, per 100,000 person-years. This molecular pathological epidemiology study supports a role of energy metabolism in colorectal cancer pathogenesis.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
Aya
A
Kuchiba
Teppei
T
Morikawa
Mai
M
Yamauchi
Yu
Y
Imamura
Xiaoyun
X
Liao
Andrew T
AT
Chan
Jeffrey A
JA
Meyerhardt
Edward
E
Giovannucci
Charles S
CS
Fuchs
Shuji
S
Ogino
D000328:Adult; D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D015986:Confounding Factors, Epidemiologic; D015536:Down-Regulation; D016021:Epidemiologic Studies; D064429:Fatty Acid Synthases / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D040081:Protein Array Analysis; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
D064429:Fatty Acid Synthases