Leptin Is Associated with an Increased Female Colorectal Cancer Risk: A Nested Case-Control Study in Japan

Abstract

Objective: To elucidate whether leptin is involved in the etiology of female colorectal cancer. Methods: A case-control study nested in the Japan Collaborative Cohort Study. We compared serum leptin levels in 58 cases of female colorectal cancer with those in 145 controls matched for study area and age. Data were analyzed using a conditional logistic regression model with adjustments for known risk factors for the development of colorectal cancer. Quintile cutoff points were determined on the distribution of leptin levels in cases and controls combined. Results: Serum geometric mean levels of leptin were 6.88 ng/ml in cases and 6.00 ng/ml in controls. The odds ratios of female colorectal cancer risk were 1.40 (95% confidence interval, CI: 0.41–4.78) for the category of the second and third quintiles combined, and 4.84 (CI: 1.29–18.1) for the category of the fourth and fifth quintiles combined relative to the first quintile after adjustment for body mass index (BMI), life-style factors, reproductive factors, and hormonal variables including insulin-like growth factor and its binding protein. Conclusion: Our results suggest that leptin most likely increases the risk of female colorectal cancer substantially independent of BMI.

Obesity Biomarkers, Metabolism and Risk of Cancer: An Epidemiological Perspective

“…A positive positive association between pre-diagnostic circulating leptin concentrations and risk of colon cancer in men was also observed in a study from Norway [73]. A higher risk of colorectal cancer in women with high prediagnostic leptin concentrations was oberved in the Japan Collaborative Cohort Study [74] and in the Women's Health Initiative cohort [75]. In a meta-analysis including six prospective studies, higher leptin concentrations were significantly associated with higher risk of colorectal cancer [76].…”

Metabolic syndrome and risk of subsequent colorectal cancer

“…The association between leptin concentration and colorectal cancer was also evaluated in women, in a case-control study conducted in Japan, suggesting that leptin increases substantially the risk of female colorectal cancer, independent of BMI [52] .…”

Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development

“…(2012) found association between the level of leptin and progression of CRC in postmenopausal women and documented that the effect of hyperleptinemia was mediated mostly by insulin. Tamakoshi et al (2005) reported that invasiveness of CRC in women is associated with a high level of leptin in serum. It is suggested that only very high levels of leptin and other metabolic factors acting simultaneously (levels of C-peptide, HbA1c, and leptin/ObR ratio) activate and increase CRC proliferation (Stocks et al, 2008).…”