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Obesity and Breast Cancer: Association of Serum Adiponectin, Leptin, and Adiponectin–Leptin Ratio as Risk Biomarkers
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2018; 39(03): 292-296
DOI: DOI: 10.4103/ijmpo.ijmpo_203_16
Abstract
Introduction: Obesity has been associated with the development of breast cancer. The objectives were to study the association of serum adiponectin, serum leptin, and adiponectin–leptin ratio (ALR) in patients with breast cancer and matched controls, and to study their relationship with the various clinicopathological characteristics of breast cancer. Materials and Methods: A prospective, hospital-based case–control study was conducted on 40 patients with a first-confirmed histopathology diagnosis of breast cancer and 40 controls comprising individuals without a history of cancer simultaneously recruited from the health examination clinics during the same study period. Serum adiponectin and leptin concentrations were measured in a single run using commercially available kits (Human ADP/Acrp30 [adiponectin] enzyme-linked immune-sorbent assay [ELISA] kit and Human Leptin ELISA kit, Elabscience Biotechnology Co., Ltd) according to the manufacturer's instructions. Results:: Serum adiponectin levels were reduced significantly in breast cancer patients, in comparison to controls (P = 0.04), while serum leptin levels were increased significantly in breast cancer patients, in comparison to controls (P = 0.03). ALR was significantly lower in breast cancer cases, in comparison to controls (P = 0.05). There was no correlation between receptor status (estrogen receptor, progesterone receptor, Her2/neu), aggressiveness of disease in terms of tumor size, nodal metastases, stage, tumor grade, and serum adiponectin levels, leptin levels, or ALR. Body mass index was negatively correlated with serum adiponectin levels and ALR (r = 0.33, P = 0.03; r = 0.39, P = 0.01, respectively) and positively correlated with serum leptin levels (r = 0.34, P = 0.02). Conclusion: In summary, our results suggest that low serum adiponectin levels, ALR, and high serum leptin levels are associated with breast cancer.
Publication History
Article published online:
17 June 2021
© 2018. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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Abstract
Introduction: Obesity has been associated with the development of breast cancer. The objectives were to study the association of serum adiponectin, serum leptin, and adiponectin–leptin ratio (ALR) in patients with breast cancer and matched controls, and to study their relationship with the various clinicopathological characteristics of breast cancer. Materials and Methods: A prospective, hospital-based case–control study was conducted on 40 patients with a first-confirmed histopathology diagnosis of breast cancer and 40 controls comprising individuals without a history of cancer simultaneously recruited from the health examination clinics during the same study period. Serum adiponectin and leptin concentrations were measured in a single run using commercially available kits (Human ADP/Acrp30 [adiponectin] enzyme-linked immune-sorbent assay [ELISA] kit and Human Leptin ELISA kit, Elabscience Biotechnology Co., Ltd) according to the manufacturer's instructions. Results:: Serum adiponectin levels were reduced significantly in breast cancer patients, in comparison to controls (P = 0.04), while serum leptin levels were increased significantly in breast cancer patients, in comparison to controls (P = 0.03). ALR was significantly lower in breast cancer cases, in comparison to controls (P = 0.05). There was no correlation between receptor status (estrogen receptor, progesterone receptor, Her2/neu), aggressiveness of disease in terms of tumor size, nodal metastases, stage, tumor grade, and serum adiponectin levels, leptin levels, or ALR. Body mass index was negatively correlated with serum adiponectin levels and ALR (r = 0.33, P = 0.03; r = 0.39, P = 0.01, respectively) and positively correlated with serum leptin levels (r = 0.34, P = 0.02). Conclusion: In summary, our results suggest that low serum adiponectin levels, ALR, and high serum leptin levels are associated with breast cancer.
Introduction
Obesity has been associated with the development of breast cancer.[1] The main underlying mechanisms that link obesity to cancer development and progression include abnormalities of insulin resistance and the insulin-like growth factor system, impact of adiposity on the biosynthesis and bioavailability of endogenous sex hormones, obesity-induced low-grade chronic systemic inflammation, and alterations in the levels of adipocyte-derived growth factors.[2]
Adiponectin, a 244-amino acid protein hormone, also known as AdipoQ, Acrp30 (adipocyte complement-related protein of 30 kDa), apM1 (gene product of the adipose most abundant gene transcript-1), and GBP28 (gelatin-binding protein-28), is the most abundant adipocyte-derived factor, with insulin-sensitizing, anti-inflammatory, and antiatherogenic properties.[3] Leptin, a peptide hormone produced by the ob gene of adipocytes, increases in concert with adiposity and has been shown to have mitogenic effects on epithelial cells and to promote cellular proliferation, migration, and invasion in breast cancer cell lines, properties potentially increasing breast cancer risk and progression.[4] Studies have examined and considered the ratio of these adipokines to be more important in breast cancer than their absolute concentrations.[5]
The objectives of the study were to determine the association of serum adiponectin, serum leptin, and adiponectin–leptin ratio (ALR) in patients with breast cancer and matched controls, and to study their relationship with the various clinicopathological characteristics of breast cancer.
Materials and Methods
Patients
A prospective, hospital-based case–control study was conducted on 40 patients with a first-confirmed histopathology diagnosis of breast cancer before treatment commencement and 40 controls comprising individuals without a history of cancer simultaneously recruited from the health examination clinics during the same study period. Data on the status of estrogen receptor (ER), progesterone receptor (PR), and Her-2/Neu were obtained. One control case was matched to each case by age, menopausal status, date of enrollment (±3 months), and duration of fasting (±4 h). Cases not histologically proven, male breast cancer patients, patients with previous history of breast or other cancers, history of diabetes mellitus on treatment, and subjects who reported a recent (within the previous 1–6 months) weight gain or loss of 5% or more of their current weight were excluded from the study.
Collection of questionnaire data
The study was conducted in accordance with the Declaration of Helsinki, and the study protocol was reviewed by the Institutional Ethics Committee. All patients gave written informed consent and underwent a personal interview. Data were collected on sociodemographic characteristics, menstrual and reproductive history, menopausal status, lifestyle behavior, and medical history as well as family history of breast and other cancers. Menopausal status was defined as last menstruation after 1 year free of menstrual cycle and no attempt was made to distinguish between women with artificial and those with natural menopause.
Assay principle
A 10 ml blood sample for measurement of serum adiponectin and leptin was collected in vacutainer tubes (EDTA-treated), and all tubes were centrifuged at 4°C for collection of serum. These were stored at −20°C until analysis. Serum adiponectin and leptin concentrations were measured in a single run using commercially available kits (Human ADP/Acrp30 [adiponectin] enzyme-linked immune-sorbent assay [ELISA] kit and Human Leptin ELISA kit, Elabscience Biotechnology Co., Ltd) according to the manufacturer's instructions. The kit is a direct ELISA for quantitative determination of adiponectin and leptin in human serum, plasma, or other biological fluids. The detection range of serum adiponectin kit was 0.78–50 ng/ml, and the minimum detectable dose of adiponectin was 0.47 ng/ml. The detection range of serum leptin kit was 0.156–10 ng/ml, and the minimum detectable dose of leptin was 0.094 ng/ml. All matched case–control blood samples were handled identically and assayed in the same analytical run.
Statistical analysis
Mean and frequencies were used to assess the distribution of sample characteristics. Student's t-tests and analysis of variance were used to evaluate the differences in adipokine concentrations by categorical variables. Multiple linear regression models were used to investigate the associations between adipokine concentrations and demographic, reproductive, and pathological variables. For all analyses, P values were 2-sided and P < 0>
Results
The baseline demographic characteristics and reproductive variables of cases and controls are summarized in [Table 1]. The sociocultural factors unique to the study population are an early age at marriage and first full-term birth, the absence of cases of habitual smoking and alcohol consumption and almost nonexistent oral contraceptive use and hormone replacement therapy. The clinicopathologic characteristics of cases included in the study are summarized in [Table 2]. The low cancer literacy among Indian women and reluctance to seek immediate medical attention is reflected in the prolonged duration of symptoms (mean ± standard deviation: 8.27 ± 13.17 months).
|
Characteristic |
Cases |
Controls |
|---|---|---|
|
Number of patients |
40 |
40 |
|
Age, mean (range) |
52 (25-75) |
50 (30-70) |
|
Education, n (%) |
||
|
No formal education |
21 (52.5) |
15 (37.5) |
|
Primary school |
4 (10) |
6 (15) |
|
Secondary school |
13 (32.5) |
16 (40) |
|
Graduate |
1 (2.5) |
1 (2.5) |
|
Postgraduate |
1 (2.5) |
2 (5) |
|
Family history of breast cancer/first |
5 (12.5) |
2 (5) |
|
degree relative with breast cancer, n (%) |
||
|
Supplementation of vitamins/ |
5 (12.5) |
8 (20) |
|
minerals, n (%) |
||
|
Alcohol consumption, n (%) |
0 |
0 |
|
Tobacco, n (%) |
||
|
Smoker |
0 |
0 |
|
Gutka chewer |
1 (2.5) |
0 |
|
Physical activity, n (%) |
||
|
Mild |
32 (80) |
29 (72.5) |
|
Moderate |
3 (7.5) |
5 (12.5) |
|
Vigorous |
5 (12.5) |
6 (15) |
|
Oral contraceptive pill use, n (%) |
1 (2.5) |
0 |
|
Hormone replacement therapy, n (%) |
4 (10) |
0 |
|
Age at menarche (years), n (%) |
||
|
<12> |
11 (27.5) |
9 (22.5) |
|
13-14 |
24 (60) |
28 (70) |
|
>15 |
5 (12.5) |
3 (7.5) |
|
Parity, n (%) |
||
|
Nulliparous status |
3 (7.5) |
1 (2.5) |
|
1 |
1 (2.5) |
4 (10) |
|
2-3 |
23 (57.5) |
25 (62.5) |
|
>4 |
13 (32.5) |
10 (25) |
|
Age at first full term birth (years), n (%) |
||
|
15-17 |
15 (40.5) |
13 (33.3) |
|
18-20 |
12 (32.4) |
10 (25.6) |
|
21-25 |
9 (24.3) |
11 (28.2) |
|
>25 |
1 (2.7) |
5 (12.8) |
|
Breast feeding, n (%) |
31 (77.5) |
35 (87.5) |
|
Age at menopause (years), n (%) |
||
|
<45> |
12 (38.7) |
12 (37.5) |
|
45-49 |
11 (35.4) |
10 (31.2) |
|
50-54 |
8 (25.8) |
10 (31.2) |
|
>55 |
0 |
0 |
|
Characteristic |
Cases (n=40) |
|---|---|
|
Her2 – Human epidermal growth factor receptor 2; ER – Estrogen receptor; PR – Progesterone receptor; IHC – Immunohistochemistry; FISH – Fluorescence in situ hybridization; SD – Standard deviation |
|
|
Duration of symptoms (in months), |
8.27 (13.17) and 1-72 |
|
mean (SD) and range |
|
|
History of benign breast disease, n (%) |
4 (10) |
|
Radiation to chest between age 10 and 30 years, n (%) |
0 |
|
Side, n (%) |
|
|
Left |
15 (37.5) |
|
Right |
25 (62.5) |
|
Location if present, n (%) |
|
|
Upper outer quadrant |
18(45) |
|
Upper inner quadrant |
6 (15) |
|
Lower outer quadrant |
5 (12.5) |
|
Lower inner quadrant |
2 (5) |
|
Central |
9 (22.5) |
|
Description of lump, n (%) |
|
|
Skin changes |
14 (35) |
|
Pain |
8 (20) |
|
Nipple discharge |
4 (10) |
|
Axillary lymphadenopathy |
23 (57.5) |
|
Stage grouping, n (%) |
|
|
Stage 0-1B |
0 |
|
Stage IIA |
10(25) |
|
Stage IIB |
9 (22.5) |
|
Stage IIIA |
6 (15) |
|
Stage IIIB |
4 (10) |
|
Stage IIIC |
5 (12.5) |
|
Hormonal receptor status |
|
|
ER positive |
21 (52.5) |
|
PR positive |
15 (37.5) |
|
Her2/neu positive (IHC) |
9 (22.5) |
|
Her2/neu positive (FISH) |
2 (5) |
|
Grade |
|
|
1 |
0 |
|
2 |
13 (32.5) |
|
3 |
15 (37.5) |
|
Characteristic |
Cases |
Controls |
P |
|---|---|---|---|
|
SD – Standard deviation |
|||
|
Serum adiponectin (pg/ml), mean (SD) |
8.69 (2.95) |
10.15 (3.56) |
0.04 |
|
Serum leptin (ng/ml), mean (SD) |
7.93 (2.90) |
6.26 (3.86) |
0.03 |
|
Adiponectin leptin ratio, mean (SD) |
1.91 (3.17) |
5.76 (11.92) |
0.05 |
|
Variable |
Adiponectin (μg/ml) |
Leptin (ng/ml) |
Adiponectin leptin ratio |
||||||
|---|---|---|---|---|---|---|---|---|---|
|
Correlation coefficient (r) |
SE |
P |
Correlation coefficient (r) |
SE |
P |
Correlation coefficient (r) |
SE |
P |
|
|
SE – Standard error; Her2 – Human epidermal growth factor receptor 2; ER – Estrogen receptor; PR – Progesterone receptor; BMI – Body mass index; *P value for BMI |
|||||||||
|
ER status |
0.21 |
2.91 |
0.17 |
0.200 |
2.885 |
0.211 |
0.22 |
3.12 |
0.15 |
|
PR status |
0.15 |
2.95 |
0.33 |
0.160 |
2.907 |
0.321 |
0.25 |
3.1 |
0.11 |
|
Her2/neu receptor status |
0.03 |
2.98 |
0.83 |
0.030 |
2.944 |
0.851 |
0.09 |
3.19 |
0.54 |
|
Grade |
0.17 |
2.94 |
0.27 |
0.195 |
2.889 |
0.226 |
0.12 |
3.18 |
0.42 |
|
Stage |
0.12 |
2.96 |
0.43 |
0.130 |
2.920 |
0.422 |
0.02 |
3.21 |
0.87 |
|
Tumour size |
0.13 |
2.96 |
0.41 |
0.167 |
2.904 |
0.301 |
0.29 |
3.07 |
0.06 |
|
Nodal status |
0.1 |
2.97 |
0.53 |
0.055 |
11.860 |
0.735 |
0.1 |
3.19 |
0.53 |
|
BMI |
0.33 |
2.82 |
0.03* |
0.346 |
2.763 |
0.028* |
0.39 |
2.94 |
0.01* |
|
Physical activity |
0.12 |
2.96 |
0.42 |
0.133 |
2.919 |
0.411 |
0.12 |
3.18 |
0.44 |
|
Parity |
0.09 |
2.97 |
0.57 |
0.087 |
2.934 |
0.589 |
0.2 |
3.14 |
0.2 |
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