Dataset Information

Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications.

ABSTRACT: Breast cancer is the female malignant neoplasia with the highest incidence in the industrialized world. Although early diagnosis has contributed to therapeutic success, breast cancer remains a major health issue. In the last few year the hormone therapy for estrogen-dependent breast cancer has evolved achieving significant clinical results; at the same time, it has enabled us to better define the role of estrogens in the etiopathogenesis of this tumour. Weight increase and obesity have been identified as the most important risk and prognostic factors for breast cancer in postmenopausal women. Several hypotheses have been proposed to explain the association of obesity with postmenopausal breast cancer. Specific obesity-associated factors, including leptin, insulin and inflammatory mediators, seem to influence breast cancer growth and prognosis independently of estrogens and at least in part by interacting with estrogen signalling at a cellular level. Therefore, a careful assessment of the nutritional status and body composition is paramount for a proper therapeutic approach for postmenopausal breast carcinoma. The use of antidiabetic and anti-inflammatory drugs associated with conventional hormone therapies and dietary/physical interventions could offer a new therapeutic approach for breast carcinoma that develops in the context of adiposity.

SUBMITTER: Maccio A

PROVIDER: S-EPMC3217612 | biostudies-other | 2011

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Background/Aims: Obesity has been consistently associated with postmenopausal breast cancer risk. Proteins secreted by adipose tissue or involved in regulating obesity may play a role in breast tumor development. We conducted a nested case- control study among white, postmenopausal women from the American Cancer Society Cancer Prevention Study II (CPS -II) Nutrition Cohort to determine whether genes associated with obesity increase risk of breast cancer. Methods: Tagging single nucleotide polymorphisms (tagSNPs) were selected to capture common variation across seven candidate genes that encode adipose- related proteins: ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, SHC1. Thirty-nine SNPs were genotyped in 648 cases and 659 controls. Logistic regression models and haplotype analysis were used to examine the association between each tagSNP and risk of breast cancer while adjusting for matching factors and potential confounders. We also examined whether these SNPs were associated with measures of adult adiposity. Results: Two of five tagSNPs in HSD11B1 were associated with breast cancer (rs11807619, P=0.006; rs932335, P=0.0002). The rs932335 C allele was associated with a nearly two-fold increased risk of breast cancer (OR=1.83; 95% CI: 1.01–3.33 for C/C versus G/G). The rs11807619 and rs932335 were highly correlated (r2=0.74), and when modeled as a haplotype, only haplotypes containing the rs932335 C allele were associated with breast cancer. Three of the eleven SNPs for IRS2 were associated with breast cancer (rs4773082, P=0.007; rs2289046, P=0.016; rs754204, P=0.03). When these 3 SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (OR=0.74, 95% CI: 0.62–0.90 for TGC compared to CAT). IRS2 rs2289046 and rs754204 were also associated with adult weight gain. None of the other SNPs in any gene investigated were associated with breast cancer or adiposity. Conclusions: Our results suggest that these tagSNPs in HSD11B1 and IRS2 mark regions of the genome that may harbor risk alleles for breast cancer, and these associations are likely independent of adiposity.

Dataset Information

Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets