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Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer.

ABSTRACT: Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case-control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the ORs and 95% confidence intervals (CI) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 cases and 706 controls were matched on ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, hours fasting before blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin [ORQ4 vs. Q1, 1.94 (1.37-2.75); Ptrend ? 0.001), the leptin:adiponectin ratio [OR, 1.91 (1.36-2.68); Ptrend = 0.005], and CRP [OR, 1.41 (1.01-1.96); Ptrend = 0.014] were associated with an increased risk of postmenopausal breast cancer. The positive associations for these markers remained after adjustment for body mass index (BMI). No associations were detected for adiponectin. These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI. Further prospective studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted. Cancer Prev Res; 6(3); 188-95. ©2013 AACR.

SUBMITTER: Ollberding NJ

PROVIDER: S-EPMC3595121 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer.

Ollberding Nicholas J NJ Kim Yeonju Y Shvetsov Yurii B YB Wilkens Lynne R LR Franke Adrian A AA Cooney Robert V RV Maskarinec Gertraud G Hernandez Brenda Y BY Henderson Brian E BE Le Marchand Loïc L Kolonel Laurence N LN Goodman Marc T MT

Cancer prevention research (Philadelphia, Pa.) 20130301 3

Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case-control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the ORs and 95% confidence intervals (CI) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 ...[more]

PMID: 23466816

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Project description:Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case-control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these potential associations.

Dataset Information

Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer.

Publications

Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer.

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