14 research outputs found

    Genetically Predicted Body Mass Index and Breast Cancer Risk : Mendelian Randomization Analyses of Data from 145,000 Women of European Descent

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    Background Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m(2) increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 x 10(-10)). The associations were similar for both premenopausal (OR = 0.44, 95% CI: 0.31-0.62, p = 9.91x10(-8)) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88x10(-8)). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 x 10(-7)). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p <0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.Peer reviewe

    Textbooks in Browsers: An Editor for Creating, Adapting, and Sharing

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    Open Textbook Proof-of-Concept via Connexions

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    To address the high cost of textbooks, Rice University’s Connexions and the Community College Open Textbook Project (CCOTP) collaborated to develop a proof-of-concept free and open textbook. The proof-of-concept served to document a workflow process that would support adoption of open textbooks. Open textbooks provide faculty and students with a low cost alternative to traditional publishers’ textbooks and can help to make higher education more affordable. Connexions provides a publishing platform for open textbook projects. The CCOTP acted as a liaison between community college faculty, open textbook authors, and Connexions. Challenges to the production and adoption of open textbooks include 1) faculty members’ and students’ expectations of high production quality and ancillaries for open textbooks, 2) methods for documenting and maintaining control over various versions, and 3) the process of converting existing open content to digital and accessible formats. Connexions holds promise as a means to overcome these challenges. Connexions identified lessons learned about open textbook production, such as the importance of a style guide, the advantage of assembly-line workflow, and the importance of naming conventions and standard math authoring tools, Connexions also identified lessons learned about open textbook use by students and faculty, e.g., the value of availability and customizability, the importance of interactivity, the difference in how faculty and students view modularity, and the importance of textbook reading navigational aids. The authors note that the CCOTP recommends using Connexions as the common repository for open textbook content in an effort to provide greater national and international access

    A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.

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    Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC (P < 4 × 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P < 6 × 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P < 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 × 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer

    Meta-analysis of the association between genetically predicted BMI and breast cancer risk in the BCAC.

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    <p>The summary OR was calculated by combining individual analysis results from each study in BCAC (<i>p</i> for heterogeneity = 0.06).</p
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