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Relationship of Serum Adiponectin and Resistin Levels with Breast Cancer Risk

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Relationship of Serum Adiponectin and Resistin Levels with Breast Cancer Risk J Korean Med Sci 2007; 22: 117-21 Copyright � The Korean Academy ISSN 1011-8934 of Medical Sciences Relationship of Serum Adiponectin and Resistin Levels with Breast Cancer Risk Obesity is one of the well-known risk factors of breast cancer. We evaluated the rela- Jee-Hyun Kang, Byung-Yeon Yu, tionship between serum adiponectin and resistin levels and breast cancer risk in 41 Dae-Sung Youn* biopsy-proven breast cancer patients and 43 age- and body mass index-matched Departments of Family Medicine, and General controls. The mean serum adiponectin level was lower in the breast cancer group Surgery*, Konyang University Hospital, Daejeon, than the control group (6.93±3.2 g/mL, vs. 7.60±3.5 g/mL), but this difference Korea did not reach statistical significance (p=0.37). There was a statistically significant difference in serum resistin levels between the groups (breast cancer group 5.23± Received : 15 February 2006 6.9 ng/mL vs. control 1.46±2.0 ng/mL; p<0.001). The risk of breast cancer was Accepted : 11 July 2006 significantly increased in the highest tertile group for serum resistin level compared to the lowest tertile group (adjusted odds ratio 2.77 [95% CI 1.40-5.50]). The lymph node metastasis was significantly increased in the patients with less than the median Address for correspondence adiponectin level (p=0.017). In the patients whose resistin level was higher than the Jee-Hyun Kang, M.D. Department of Family Medicine, Konyang University median, the frequency of tumor with the highest histological grade was significant- Hospital, 685 Gasuwon-dong, Seo-gu, Daejeon ly increased (p=0.025). In conclusions, both the low serum adiponectin levels and 320-718, Korea high resistin levels are likely to be associated with increased breast cancer risk in Tel : +82.42-600-9240, Fax : +82.42-600-9095 Korean women. E-mail : [email protected] *This study was supported by Konyang University Key Words : Adiponectin; Resistin; Breast Neoplasms; Disease Susceptibility Myung Gok Research Fund of 2004. INTRODUCTION has been established that plasma adiponectin concentration is inversely correlated with the incidence of obesity, type 2 Obesity is a well-known risk factor for breast cancer, and diabetes, and cardiovascular disease (7-9). Adiponectin was obese women are likely to have metastatic breast cancer when shown to have anti-inflammatory activity, a protective effect they are first diagnosed, and to have a poor prognosis regard- against metabolic disorders resulting from the insulin resis- less of their menopausal status (1, 2). Although the exact tance, and improve endothelial dysfunction (10-12). mechanism remains to be determined, the hormonal changes Resistin, named for resistance to insulin, is a unique sig- associated with obesity are considered to be responsible for nalling molecule secreted from adipocytes. Circulating resistin this relationship, with particular emphasis being placed on levels are decreased by the anti-diabetic drug rosiglitazone, the increased production of estrogen. Adipose tissue is well and increased in diet-induced and genetic forms of obesity. In established that the source of estrogen production through addition, treatment of normal mice with recombinant resistin aromatization of androgens which is derived from the adrenal impairs glucose tolerance and insulin action. Insulin-stimu- gland (3). However, according to recent studies, the contri- lated glucose uptake by adipocytes is enhanced by neutraliza- bution to the development of breast cancer from obesity is tion of resistin and is reduced by resistin treatment. Thus, not fully explained by increased estrogen levels only (4, 5). resistin may serve as a hormone that potentially links obesity Adipose tissue is not only a passive reservoir for energy to insulin resistance (13). However, the studies performed on storage but is now known to express and secrete a variety of humans lack coherence between the results, and further stud- metabolites, hormones, and cytokines, known as adipocyto- ies are needed to ascertain the role of resistin (14, 15). kines, which act at both the local and systemic level. These Interestingly, several recent case-control studies have shown adipocytokines include leptin, adiponectin, complement com- that decreased adiponectin levels are associated with the inci- ponents, plasminogen activator inhibitor-1, tumor necrosis dence of breast cancer, but the correlation between serum factor- (TNF- ), interleukin-6 (IL-6), proteins of the renin- adiponectin and breast cancer risk is not clear yet, and the angiotensin system, and resistin (6). molecular basis for the link remains poorly understood (16- Adiponectin is secreted from adipocytes exclusively and it 18). To our knowledge, the association of resistin with can- 117 118 J.-H. Kang, B.-Y. Yu, D.-S. Youn cer has not been reported until now. model was constructed. The correlation of plasma adiponectin In this case-control study, we examined the relationship of or resistin concentration with clinicopathologic characteris- serum adiponectin and resistin level with breast cancer risk tics of tumors was analyzed by chi-square test. Pearson’s cor- in biopsy-proven breast cancer patients and age and body mass relation coefficients were used to determine the relationships index-matched controls. between plasma adiponectin, resistin, glucose, body mass index, and age. A log transformation of plasma resistin levels was carried out to achieve normal distribution. The level of MATERIALS AND METHODS significance was set at p<0.05 (two-tailed). Statistical calcu- lations were performed using SPSS for Windows V11.0 (SPSS Subjects Inc., Chicago, IL, U.S.A.). From January 2005 to December 2005, forty-one female patients who were newly diagnosed with breast cancer and RESULTS surgically treated at a University Hospital were enrolled into the study as patients group. Among women who visited the Comparison of adiponectin and resistin levels same hospital for annual health examinations, we selected 43 women with normal mammographic findings and no previ- There was no significant difference in age, body mass index, ous history of any kind of cancer as age and body mass index- and percentage of menopausal women (Table 1). The fasting matched controls. glucose levels in the control group were significantly lower than those in the patients group (97.4±20.4 mg/dL vs. 115.2 Anthropometric measurement and blood tests ±30.3 mg/dL). The mean serum adiponectin level was lower in the breast cancer group than the control group (6.93±3.2 Body weight was measured with light clothing on with g/mL, vs. 7.60±3.5 g/mL), but this difference did not up to 0.1 kg precision. Height was measured up to 0.1 cm. reach statistical significance (p=0.37). There was a statisti- The blood samples were collected within the week before cally significant difference in serum resistin levels between surgery. Plasma glucose, adiponectin, and resistin concentra- the groups (breast cancer group 5.23±6.9 ng/mL vs. control tions were measured after overnight fasting for more than 1.46±2.0 ng/mL; p<0.001) (Fig. 1). 12 hr. Plasma adiponectin was measured using human adi- When serum adiponectin and resistin levels were compared ponectin ELISA kit (AdipoGen, Inc., Seoul, Korea) with a in cases and controls according to menopausal status, serum measurement range of 0.1-32 ng/mL, sensitivity of 0.1 ng/ resistin levels were significantly higher in the breast cancer mL, intra-assay reproducibility of 96.5%, and inter-assay repro- group in both pre- and post-menopausal women (p=0.02, ducibility of 95.6%. Plasma resistin level was measured using p=0.002; respectively). However, there was no significant human resistin ELISA kit (AdipoGen, Inc., Seoul, Korea) with difference in serum adiponectin levels between cases and con- a measurement range of 0.1-8 g/mL, sensitivity of 0.1 g/ trols in either pre- or post-menopausal women (p=0.22, p= mL, intra-assay reproducibility of 96.3%, and inter-assay repro- 0.89; respectively) (Table 1). ducibility of 94.4%. Table 1. Clinical characteristics of cases and controls (mean± Clinicopathologic characteristics of tumor SD) Patients with breast cancer were classified according to the Cases (n=41) Controls (n=43) p size of tumors (>2 cm or ≤2 cm) and status of lymph node Age (yr) 47.4±9.0 47.8±6.0 0.95 metastasis (presence or absence). Histological grading of breast Body mass index (kg/m2) 23.7±3.7 23.7±3.0 0.99 cancer was based on the Bloom-Richardson grading system. Postmenopausal women (No.) 20 (48.8%) 17 (39.5%) 0.39 The status of estrogen receptor and progesterone receptor were Fasting blood glucose (mg/dL) 115.2±30.0 97.4±20.4 0.01 analyzed by imminohistochemical staining (DAKO, Carpin- Adiponectin ( g/mL) 6.93±3.2 7.60±3.5 0.37 teria, CA, U.S.A.). Premenopausal women 7.13±3.2 8.68±4.0 0.22 (n=35) Postmenopausal women 6.77±3.3 6.89±3.0 0.89 Statistical analysis (n=49) Resistin (ng/mL) 5.23±6.9 1.46±2.0 <0.001* Data are presented as means±S.D. Independent t-test was Premenopausal women 5.80±7.7 1.85±2.2 0.02* used to compare variables between case and control group (n=35) except for menopausal status (chi-square test). To determine Postmenopausal women 4.79±6.5 1.20±1.9 0.002* the risk of breast cancer according to the tertiles of plasma (n=49) adiponectin and resistin levels, a multiple logistic regression *Resistin level was transformed logarithmically before analysis. Adiponectin and Resistin Levels and Breast Cancer Risk 119 15 20 12 15 9 10 6 Resistin (ng/mL) Adiponectin ( g/mL) 5 3 0 Case Control A Case Control B Fig.
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