title: 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.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard, Bethesda, Maryland 20852, USA. cher.dalla@nih.gov
authors.forename: Cher M
authors.initials: CM
authors.lastname: Dallal
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Bauer
authors.forename: Diana S M
authors.initials: DS
authors.lastname: Buist
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Trisha F
authors.initials: TF
authors.lastname: Hue
authors.forename: Andrea
authors.initials: A
authors.lastname: Lacroix
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Tice
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Chia
authors.forename: Roni
authors.initials: R
authors.lastname: Falk
authors.forename: Ruth
authors.initials: R
authors.lastname: Pfeiffer
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: James V
authors.initials: JV
authors.lastname: Lacey
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood* / Q000209:etiology / Q000473:pathology; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008137:Longitudinal Studies; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications*; D017698:Postmenopause / Q000097:blood*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D054392:Adipokines; D052242:Adiponectin; D002096:C-Peptide; D004967:Estrogens; D020738:Leptin