Obesity Potentiates AOM-Induced Colon Cancer

Obesity and diet affect the incidence and severity of various types of cancer, including colon cancer. It is not known whether obesity, independent of diet, is a risk factor for colon adenocarcinoma. We used azoxymethane (AOM) to induce colon cancer in mature genetically obese male Zucker rats (fa/fa) on low-fat crude diet (LFC, 10% fat) and their lean counterparts (Fa/fa and Fa/fa) on high-fat crude diet (HFC, 40% fat) for three months. At death visible tumors, histopathology, and colonic aberrant crypt (AC) formation were studied by blinded investigators. At death the obese animals were heavier (719 ± 19 g; mean ± sem) than lean animals regardless of diet or genotype (Fa/fa-LFC:451 ± 6 g; Fa/fa-HFC:441 ± 10 g; Fa/Fa-HFC:412 ± 9 g; P < 0.001 vs fa/fa by ANOVA). All AOM-treated rats developed AC, compared to none of the saline-injected controls. Macroscopic adenocarcinoma developed in 8/9 obese rats on LFC (P < 0.001), compared to none in lean rats regardless of diet. Obese rats had significantly more AC (876 ± 116) than any of the lean rats (Fa/fa-LFC:550 ± 99; Fa/fa-HFC:325 ± 37; Fa/Fa-HFC:360 ± 36; P < 0.05 vs fa/fa). We conclude that obesity more than exposure to high-fat diet was associated with colon carcinogenesis in these rats.