Possible Involvement of Hyperlipidemia in Increasing Risk of Colorectal Tumor Development in Human Familial Adenomatous Polyposis

• Published in: Japanese journal of clinical oncology 2006-03, Vol.36 (3), p.166-171
• Main Authors: Mutoh, Michihiro, Akasu, Takayuki, Takahashi, Mami, Niho, Naoko, Yoshida, Teruhiko, Sugimura, Takashi, Wakabayashi, Keiji
• Format: Article
• Language: English
• Subjects: Adenomatous Polyposis Coli - complications; Adenomatous Polyposis Coli - genetics; Adolescent; Adult; Aged; Aged, 80 and over; Animals; APC gene; BMI; body mass index; ChE; cholinesterase; colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - etiology; COX; cyclooxygenase; familial adenomatous polyposis; FAP; Female; Genes, APC; Germ-Line Mutation; Humans; hyperlipidemia; Hyperlipidemias - epidemiology; Intestinal Polyps - epidemiology; Intestinal Polyps - etiology; lipoprotein lipase; LPL; Male; Mice; Middle Aged; non-steroidal anti-inflammatory drugs; NSAIDs; peroxisome proliferator-activated receptor; Pilot Projects; PPAR; Prevalence; Rectal Neoplasms - epidemiology; Rectal Neoplasms - etiology; Risk; total cholesterol; triglyceride; Triglycerides - blood
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyi233

Background: Familial adenomatous polyposis (FAP) results from germline adenomatous polyposis coli (APC) gene mutations and many affected patients die from colorectal cancers which arise from colorectal polyps. We previously reported that two strains of Apc gene-deficient mice developing multiple intestinal polyps exhibit a hyperlipidemic state. The triglyceride (TG) levels were ∼10-fold higher than the levels observed in wild-type mice. Methods: To examine whether a positive relationship might exist between hyperlipidemia and colorectal tumor development in FAP patients, as with Apc gene-deficient mice, a pilot experiment was performed using readily available clinical data such as ages, serum lipid levels, number of colorectal polyps and cancer development in 28 FAP patients from the National Cancer Center Hospital, Japan. Results: The overall prevalence of hyperlipidemia in FAP cases was 58%. Average TG levels in the 40–60 year age groups of FAP patients were ≥150 mg/dl (the defined threshold level of hyperlipidemia). Moreover, there was a tendency for higher serum TG levels in patients who developed colorectal cancer, as compared with those without colorectal cancer. Conclusions: These results show that a hyperlipidemic state occurs in FAP patients. Although it is weaker than that in Apc gene-deficient mice, it may be linked to colon tumor development. These data warrant further studies for wider poplulations of FAP patients.