Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes

Abstract

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.

The Relationship between Adiponectin and Breast Cancer

“…Adiponectin 45T/G and 276T/G gene polymorphisms are of gene polymorphisms associated with breast cancer (8,27,28). In a study by Al Khaldi et al (27), the adiponectin gene 45T>G was found more frequently in patients with breast cancer in Kuwait, and the adiponectin gene was considered to predispose for breast cancer.…”

Association of Leptin Receptor Lys109Arg and Gln223Arg Polymorphisms with Increased Risk of Clear Cell Renal Cell Carcinoma

“…The frequencies of LEPR polymorphisms also were different in previous reports. The frequencies of Lys109Arg wild-type (A) were 31.52%, 35.2%, 18.09% and Gln223Arg were 51.94%, 58.6%, 8.9% in whites and African American (Nyante et al, 2011), Caucasian (Teras et al, 2009) and Asian (Woo et al, 2006;Liu et al, 2007) normal population, respectively. In our study, the frequencies of Lys109Arg and Gln223Arg wild-types were 20.5% and 15.22% in controls, which was similar to Asian population.…”

Increased peroxisome proliferator-activated receptor γ expression levels in visceral adipose tissue, and serum CCL2 and interleukin-6 levels during visceral adipose tissue accumulation

“…Changes in the adipokine levels affect cell proliferation, apoptosis and invasive growth of cancer cells (8). The adipokines produced by visceral adipose tissue have been shown to be associated with the risk and the progression of breast cancer (9,10). Therefore, elucidating the genes that regulate visceral adipose tissue accumulation and the adipokine network is important to understand the progression of visceral adipose tissue-related diseases further.…”