LDL Cholesterol in the Adenoma-Carcinoma Sequence of Colorectal Cancer: More Answers and New Questions

Abstract

Introduction: Malignant colon tumors are thought to be involved in cholesterol catabolism since increased expression of LDL receptor mRNA has been described in colon cancer tissue. We previously showed that LDL cholesterol levels are higher in colorectal cancer (CRC) subjects compared to subjects with colon adenomatous polyps, and that total cholesterol level inversely correlates with polyp size. We compared the serum lipids in colon cancer patients before and after surgical resection with those in controls without known history of colon polyps or CRC. Methods: We performed a retrospective study in adult subjects who underwent curative or noncurative surgery for CRC. Controls included patients coming to the ambulatory clinic during the same period for routine visits, without a known history of colon polyps, CRC, or other malignancy. We collected demographic data, serum lipid levels before and after surgery, histology of the tumor, statin use, and metastases. Data were analyzed using SPSS; results are shown as median (range). Results: Two hundred thirty-four patients with CRC and 130 controls were included in the study. The gender distribution was similar in the 2 groups (females 58% vs 55%, respectively). The median age was 66 years (range 25-97 years). Twenty percent of CRC subjects had metastatic disease at the time of surgery. Most of the tumors (57%) were located in the left colon, and 94% were adenocarcinomas. Significantly lower levels of LDL cholesterol (median 97 mg/dL vs. 111 mg/dL; p<0.006) and HDL cholesterol (41 mg/dL vs. 45 mg/dL; p<0.016) were found in CRC subjects compared to controls. After surgery, the LDL cholesterol and HDL cholesterol levels were still lower in CRC patients than in controls (80 mg/dL vs. 111 mg/dL; p<0.001, and 40 mg/dL vs. 45 mg/dL; p<0.003, respectively). The difference after surgery was found to be due to the CRC subjects without metastatic disease who had a further decrease in LDL level (99 mg/dL to 78 mg/dL; p=0.020) following curative surgery; the difference was true when controlling for statin use. No significant changes in the serum lipid levels before and after surgery were noted in CRC subjects with metastatic disease; their lipid levels after sugery were not significantly different from those of controls. Conclusion: Low cholesterol levels are present in CRC subjects compared to controls without known history of colon polyps, and they decrease further after curative surgery. No significant changes occur in subjects with metastatic disease undergoing surgery. Serum cholesterol seems to be more than a bystander in the adenoma-carcinoma sequence of CRC; elucidating this complex relationship may offer further opportunities for diagnosis and treatment.