Body mass index is an established risk factor for postmenopausal breast cancer. Epidemiologic studies have also reported a positive association between type 2 diabetes (T2D) and breast cancer risk.
To investigate a genetic basis linking these common phenotypes with breast cancer, we tested 31 common variants for T2D and obesity in a case-control study of 1,915 breast cancer cases and 2,884 controls nested within the Multiethnic Cohort (MEC) study.
Following adjustment for multiple tests, we found no significant association between any variant and breast cancer risk. Summary scores comprising the numbers of risk alleles for T2D and/or obesity were also not found to be significantly associated with breast cancer risk.
Our findings provide no evidence for association between established T2D and/or obesity risk variants and breast cancer risk among women of various ethnicities.
These results suggest that the potential for a shared biology between T2D/obesity and breast cancer is not due to pleiotropic effects of these risk variants.
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"A national survey conducted in 1994 in China showed that the prevalence of DM was 2.5% , whereas in 2007, the prevalence had reached 9.7% . Some researchers have found an association betwen obesity or DM and the mortality rates from breast cancer [7,8], but others have found no such assocation . Because of these inconsistencies regarding the association between obesity or DM and breast cancer, it is necessary to study this relationship further. "
[Show abstract][Hide abstract] ABSTRACT: Background
This study was designed to explore the relationship between obesity, diabetes mellitus (DM), and female breast cancer in Eastern China.
A 1:3 matched case–control study was carried out, comprising 123 women with breast cancer and 369 controls. All of the 492 subjects were selected from a previous epidemiological survey of 122,058 women in Eastern China.
There were significant differences between the case and control groups in waist circumference and body mass index (BMI), but not in waist to hip ratio or hip circumference. There was a significant difference between the two groups in BMI for post-menopausal women, and a significant difference in waist circumference for pre-menopausal women. After adjustment for other factors, BMI was still significantly associated with breast cancer (odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.14 to 2.19). DM was significantly associated with breast cancer (OR = 3.35, 95% CI 1.02 to 11.01) in the univariate analysis but not in the multivariate analysis (P = 0.059).
Obesity might be a risk factor for female breast cancer. We found different strengths of association for women with different menopausal status when we examined the relationship between obesity and breast cancer. The association between DM and female breast cancer should be further confirmed with larger sample sizes.
World Journal of Surgical Oncology 03/2013; 11(1):71. DOI:10.1186/1477-7819-11-71 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Wnt signaling controls cell specification and fate during development and adult tissue homeostasis by converging on a small family of DNA binding factors, the T-cell factor/lymphoid enhancer factor (TCF/LEF) family. In response to Wnt signals, TCF/LEF members undergo a transcriptional switch from repression to activation mediated in part by nuclear β-catenin binding and recruitment of co-activator complexes. In mammals, the specificity and fine tuning of this transcriptional switch is also achieved by the cell-context-dependent expression of four members (TCF7, TCF7L1, TCF7L2, and LEF1) and numerous variants, which display differential DNA binding affinity and specificity, repression strength, activation potential, and regulators. TCF7/LEF1 variants are generated by alternative promoters, alternative exon cassettes, and alternative donor/acceptor splicing sites, allowing combinatorial insertion/exclusion of modular functional and regulatory domains. In this review we present mounting evidence for the interdependency of TCF7/LEF1 variant expression and functions with cell lineage and cell state. We also illustrate how the p53 and nuclear receptor family of transcription factors, known to control cell fate and to inhibit Wnt signaling, may participate in the fine tuning of TCF7/LEF1 repression/activation potentials.
[Show abstract][Hide abstract] ABSTRACT: PPARγ is a transcription factor important for adipogenesis and adipocyte differentiation. Data from animal studies suggest that PPARγ may be involved in breast tumorigenesis, but results from epidemiologic studies on the association between PPARγ variation and breast cancer risk have been mixed. Recent data suggest that soy isoflavones can activate PPARγ. We investigated the interrelations of soy, PPARγ, and mammographic density, a biomarker of breast cancer risk in a cross-sectional study of 2,038 women who were members of the population-based Singapore Chinese Health Study Cohort.
We assessed mammographic density using a computer-assisted method. We used linear regression to examine the association between 26 tagging single-nucleotide polymorphisms (SNP) of PPARγ and their interaction with soy intake and mammographic density. To correct for multiple testing, we calculated P values adjusted for multiple correlated tests (P(ACT)).
Out of the 26 tested SNPs in the PPARγ, seven SNPs were individually shown to be statistically significantly associated with mammographic density (P(ACT) = 0.008-0.049). A stepwise regression procedure identified that only rs880663 was independently associated with mammographic density which decreased by 1.89% per-minor allele (P(ACT) = 0.008). This association was significantly stronger in high-soy consumers as mammographic density decreased by 3.97% per-minor allele of rs880663 in high-soy consumers (P(ACT) = 0.006; P for interaction with lower soy intake = 0.017).
Our data support that PPARγ genetic variation may be important in determining mammographic density, particularly in high-soy consumers.
Our findings may help to identify molecular targets and lifestyle intervention for future prevention research.