RESUMO
BACKGROUND: Potential association of leptin (LEP) gene polymorphisms has been suggested in the processes leading to breast cancer initiation and progression. We investigated whether genetic variations in the LEP -2548G/A gene are associated with risk of breast cancer. METHODS: This case-control study consisted of 100 breast cancer cases and 100 control subjects without breast cancer that matched for age and body mass index (BMI). Genotyping of LEP -2548G/A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Serum leptin level was determined by ELISA in all study subjects. RESULTS: The genotype distributions (AA, AG, and GG) were 36, 55, and 9% in breast cancer cases and 52, 45, and 3% in control group, respectively. The frequency of LEP -2548 GG genotype was significantly elevated in breast cancer cases as compared to controls (χ2=6.90, p=0.032). Similar difference was also found in allele frequencies between two groups (χ2=5.65, p=0.017). A markedly increase risk of breast cancer was associated with the LEP -2548GG genotype when compared to the LEP -2548 AA genotype (OR=4.33, 95% CI=1.09-17.22). In addition, postmenopausal women who bear at least one LEP -2548 G allele were at a markedly increased risk of breast cancer after adjusting for age and BMI confounders (OR=12.24, 95% CI=1.13-131.73). CONCLUSION: The LEP -2548 G/A polymorphism is associated with markedly increased risk of breast cancer especially in postmenopausal Ahvazian women and supported the hypothesis that leptin is involved in breast cancer.
RESUMO
OBJECTIVES: Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that is known implicated in the initiation and progression of breast cancer. We have investigated the effect of Q223R polymorphism on the breast cancer susceptibly in a sample of Iranian subjects. MATERIALS AND METHODS: We utilized a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method to investigate the association of LEPR Q223R polymorphism with breast cancer risk in a case control study consisting of 100 breast cancer cases and 100 controls without breast cancer. Serum levels of leptin and soluble leptin receptor (sOB-R) were measured by ELISA method. RESULTS: The genotype (QQ, QR, and RR) distributions were 25, 56, and 19 % in breast cancer cases and 54, 40, and 6% in controls, respectively. The frequency of 223 RR genotype was significantly elevated in breast cancer cases as compared to controls (χ(2)= 20.072, P<0.001). Similar significance differences were also found in allele frequencies for Q and R between two groups (χ(2)= 19.027, P< 0.001). Additionally, there were significant association between Q223R genotypes and breast cancer risk; homozygotes for RR genotype (OR= 6.840; 95% confidence interval [CI] = 2.434-19.218), heterozygotes for QR (OR=3.024; 95% CI = 1.620-5.644, P = 0.001), and QR+RR genotype (OR= 3.522; 95% CI = 1.934-6.414, P < 0.001), respectively. CONCLUSION: Our results showed that the LEPR Q223R polymorphism is associated with increased breast cancer risk as well as tumor grade in a sample of Iranian subjects.
RESUMO
BACKGROUND: Leptin plays a key role in the regulation of energy expenditure and is known to circulate in both free and bound forms. Soluble leptin receptor (sOB-R) is a unique circulating form of leptin receptor that can bind to leptin. Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. Our study was aimed to investigate the relationship between serum levels of sOB-R and leptin with breast cancer. MATERIALS AND METHODS: Serum leptin and sOB-R levels were measured by enzyme-linked immunosorbent assay in 100 women with breast cancer cases compared with 100 age and body mass index (BMI)-matched controls without cancer. Lipid profiles were measured by enzymatic method. RESULTS: The median serum levels of sOB-R in controls were significantly higher than that in breast cancer cases (odds ratio [OR], 1.98; 95% confidence interval [CI] = 0.77-188.2) versus (OR, 0.140; 95% CI = 0.09-98.1). Conversely, the median serum level of leptin in breast cancer cases was significantly higher than that in controls (OR, 67.90; 95% CI = 2.77-129.9) vs. (OR, 28.30; 95% CI = 0.60-113.1). Breast cancer was significantly associated with higher serum level of leptin (OR = 1.027, 95% CI = 1.017-1.038). Conversely, breast cancer was correlated with lower serum level of sOB-R (OR = 0.983, 95% CI = 0.969-0.997). Moreover, free leptin index (FLI) (leptin/sOB-R ratio) was associated with breast cancer (OR = 1.028, 95% CI = 1.015-1.042). The serum sOB-R level was negatively associated with leptin, BMI, and high density lipoprotein (r = -0.238, -0.186, and -0.168, respectively). CONCLUSION: Our results suggested that FLI and serum leptin level rather than serum level of sOB-R was associated with the breast cancer.
