Abstract
IntroductionObesity has been linked to increased risk of breast cancer in postmenopausal women. Increased peripheral production of estrogens has been regarded as the main cause for this association, but other features of increased body fat mass may also play a part. Leptin is a protein produced mainly by adipose tissue and may represent a growth factor in cancer. We examined the association between leptin plasma levels and mammographic density, a biomarker for breast cancer risk.MethodsWe included data from postmenopausal women aged 55 and older, who participated in a cross-sectional mammography study in Tromsø, Norway. Mammograms, plasma leptin measurements as well as information on anthropometric and hormonal/reproductive factors were available from 967 women. We assessed mammographic density using a previously validated computer-assisted method. Multiple linear regression analysis was applied to investigate the association between mammographic density and quartiles of plasma leptin concentration. Because we hypothesized that the effect of leptin on mammographic density could vary depending on the amount of nondense or fat tissue in the breast, we also performed analyses on plasma leptin levels and mammographic density within tertiles of mammographic nondense area.ResultsAfter adjusting for age, postmenopausal hormone use, number of full-term pregnancies and age of first birth, there was an inverse association between leptin and absolute mammographic density (Ptrend = 0.001). When we additionally adjusted for body mass index and mammographic nondense area, no statistically significant association between plasma leptin and mammographic density was found (Ptrend = 0.16). Stratified analyses suggested that the association between plasma leptin and mammographic density could differ with the amount of nondense area of the mammogram, with the strongest association between leptin and mammographic absolute density in the stratum with the medium breast fat content (Ptrend = 0.003, P for interaction = 0.05).ConclusionWe found no overall consistent association between the plasma concentration of leptin and absolute mammographic density. Although weak, there was some suggestion that the association between leptin and mammographic density could differ with the amount of fat tissue in the breast.
Highlights
Obesity has been linked to increased risk of breast cancer in postmenopausal women
Because we hypothesized that the effect of leptin on mammographic density could vary depending on the amount of nondense or fat tissue in the breast, we performed analyses on plasma leptin levels and mammographic density within tertiles of mammographic nondense area
When we adjusted for body mass index and mammographic nondense area, no statistically significant association between plasma leptin and mammographic density was found (Ptrend = 0.16)
Summary
Obesity has been linked to increased risk of breast cancer in postmenopausal women. Obesity has been associated with increased risk of postmenopausal breast cancer in epidemiological studies [1,2,3]. The increased conversion of androgens to estrogens by the aromatase enzyme in peripheral adipose tissues [4] along with reduced levels of serum sex hormone binding globulin have been hypothesized to be the main link between obesity and increased risk of postmenopausal breast cancer [2]. Production of postmenopausal estrogens, adipocytes secrete a number of biological active polypeptides, the adipocytokines [6], some of which may be involved in breast cancer development [7]. Leptin regulates appetite and energy expenditure by signaling nutritional status to the hypothalamus [15], but is involved in a number of other processes including the regulation of reproduction and immune response [16,17]
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