Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort.

Abstract

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.

• Authors: Cher M Dallal, Louise A Brinton, Douglas C Bauer, Diana S M Buist, Jane A Cauley, Trisha F Hue, Andrea Lacroix, Jeffrey A Tice, Victoria M Chia, Roni Falk, Ruth Pfeiffer, Michael Pollak, Timothy D Veenstra, Xia Xu, James V Lacey Jr, B~FIT Research Group
• Journal: Endocrine-related cancer (Endocr Relat Cancer) Vol. 20 Issue 1 Pg. 151-60 (Feb 2013) ISSN: 1479-6821 [Electronic] England
• PMID: 23222000 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Adipokines
• Adiponectin
• C-Peptide
• Estrogens
• Leptin

Topics

• Adipokines (blood)
• Adiponectin (blood)
• Aged
• Aged, 80 and over
• Body Mass Index
• C-Peptide (blood)
• Case-Control Studies
• Endometrial Neoplasms (blood, etiology, pathology)
• Estrogens (blood)
• Female
• Humans
• Leptin (blood)
• Longitudinal Studies
• Middle Aged
• Obesity (blood, complications)
• Postmenopause (blood)
• Prognosis
• Risk Factors