Adipocytokine resistin and breast cancer risk

Abstract

Adipocytokine resistin is a member of the newly discovered family of cysteine-rich protein. Recent data suggest that macrophages are a major source of human resistin. Given the obesity-breast cancer link and convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and breast cancer risk in humans. We conducted a hospital-based case-control study to evaluate whether plasma resistin levels were associated with breast cancer risk in women. We also examined the modification effect of estrogen exposures on the resistin-breast cancer link. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 380 incident cases with breast cancer and 760 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2008. Plasma levels of resistin were measured by enzyme immunoassay. Cumulative exposure to estrogens were estimated according to the age at menarche and age at enrollment for premenopausal women and age at menarche and age at menopause for postmenopausal women. Cases with breast cancer had significantly elevated resistin concentrations as compared with control subjects. Compared with those in the lowest quartile, the adjusted odds ratios of breast cancer for women in the second, third, and highest quartiles were 1.48 [95% confidence interval (CI) = 0.65-3.38], 1.76 (95% CI = 1.00-4.73), and 2.08 (95% CI = 1.04-3.85), respectively. Furthermore, the biological gradient of breast cancer risk by plasma resistin levels remained after adjustment for measures of adiposity. The dose-dependent relationship of resistin levels with breast cancer risk was notably pronounced among women with excess exposure to estrogens. Adipocytokine resistin may have an adiposity-independent role in breast carcinogenesis. Mechanistic studies to fully elucidate the mechanisms underlying resistin's effects should be pursued in future investigations.