Adiponectin and colorectal adenomas: Self Defense Forces Health Study

Abstract

Adiponectin is an adipocyte-derived protein with an insulinsensitizing action. Circulating levels of adiponectin are inversely correlated with obesity, especially abdominal obesity. Some studies have suggested that low levels of circulating adiponectin might be related to increased risk of colorectal cancer and adenomas. The present study examined the relationship between total and highmolecular-weight (HMW) adiponectin to colorectal adenomas in the Self Defense Forces (SDF) Health Study. The study subjects comprised 656 cases of colorectal adenomas and 648 controls with normal colonoscopy among men receiving a preretirement health examination at two Self Defense Forces hospitals. Total and HMW adiponectin were slightly lower in adenoma cases than in controls; geometric means of total adiponectin were 5.42 μ μ μ μg/mL in cases and 5.63 μ μ μ μg/mL in controls (P = 0.13), and the corresponding values of HMW adiponectin were 2.47 μ μ μ μg/mL and 2.57 μ μ μ μg/mL, respectively (P = 0.29). Regardless of adjustment for body mass index and other lifestyle factors, total adiponectin was unrelated to the risk of colorectal adenomas. Total adiponectin levels were inversely related to the risk of large adenomas (≥ ≥ ≥ ≥ 5 mm), but not of small adenomas, with a nearly statistically significant decreasing trend (P = 0.06). However, the inverse association was largely ascribed to body mass index and other lifestyle factors. HMW adiponectin showed no clear association with either overall or size-specific risk of colorectal adenomas. The study provided suggestive evidence for a protective association between adiponectin and large adenomas, but did not indicate a protective association independent of adiposity. (Cancer Sci 2008; 99: 781-786)A diponectin is an adipocyte-derived protein that is expressed specifically and abundantly in adipose tissue.(1,2)The primary known function of this molecule is an insulinsensitizing action, and decreased levels of adiponectin seem to be fundamentally involved in the development of insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome.(1-3) Paradoxically, circulating levels of adiponectin are inversely correlated with obesity, especially abdominal obesity.(2,4) It is thus of natural interest to examine the relationship between circulating levels of adiponectin and risk of obesity-related cancers. Increased risks of endometrial (5,6) and breast cancer (7,8) were consistently observed in women with low levels of circulating adiponectin in case-control studies. Low levels of circulating adiponectin have also been linked to increased risk of renal cell carcinoma.(9) Two prospective studies have addressed the relationship between plasma adiponectin levels and colorectal cancer risk; one study showed a decreased risk in men at the second to fifth quintiles compared with those at the lowest quintile, (10) but the other found no association between adiponectin and colorectal cancer.(11) A recent casecontrol study reported that plasma levels of adiponectin were substantially lower ...

The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer

“…Although the function of most SNPs remains unclear, it has been shown that two common SNPs, rs1501299 (G276T) and rs2241766 (T45G), may affect disease susceptibility. They have been associated with serum adiponectin (20)(21)(22)(23)(24)(25)(26), obesity (21,25,27,28), insulin sensitivity (18,21,29), type II diabetes (17,20,30) and coronary artery disease (24,31). However, some of these associations have been unable to be confirmed in other studies and the results have been controversial (32)(33)(34).…”

“…Furthermore, they observed that adiponectin serum concentration inversely correlated with tumor size and cancer stage. Fukumoto et al observed in patients with adenoma a slightly lower adiponectin serum concentration than in healthy controls (17). Kumor et al observed in patients with colorectal adenomas and carcinoma lower serum adiponectin concentrations than in the control group (18).…”

“…It contains 244 amino acids, a signal peptide, a collagen-like domain at its N-terminus and a globular domain at its C-terminus, which shares sequence similarities with collagens X and VIII, as well as the complement factor C1q (3)(4)(5). In human plasma, the circulating adiponectin level ranges between 5 to 30 µg/ml (6) and is reduced in patients with insulin resistance (7,8), type II diabetes (9-12), obesity (13), cardiovascular disease (14,15), gastric cancer (16) and colorectal adenomas and carcinoma (17,18). Low plasma adiponectin levels in these disease states are accompanied by reduced adiponectin gene expression in adipose tissue (7,19) and have been associated with ADIPOQ gene SNPs.…”

Association of Adiponectin Receptor (Adipo-R1/-R2) Expression and Colorectal Cancer

“…On the other hand, some studies showed lack of any association between ApN plasma levels and the development of colorectal cancer and an inverse relationship with ApN levels was reported only for large adenomas (≥5 mm) (Lukanova et al, 2006;Fukumoto et al, 2008). Yamauchi et al demonstrated that ApN acts via its two receptors, namely Adiponectin receptor-1 (Adipo-R1) and Adiponectin receptor-2 (Adipo-R2) (Yamauchi et al, 2003).…”

Associations between Adiponectin and Two Different Cancers: Breast and Colon

“…Later in his prospective case control study, Wei EK et al suggested that the risk of colorectal cancer is higher in patients with low adiponectin plasma levels (Wei et al,2005). Conversely Fukumoto J et al revealed that there is no measurable association between circulating levels of adiponectin and colorectal adenomas (Fukumoto et al,2008). The mechanisms of these effects are also a mystery.…”