Background risk of breast cancer and the association between physical activity and mammographic density

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Cross-Sectional Study of Sleep Quantity and Quality and Amnestic and Non-Amnestic Cognitive Function in an Ageing Population: The English Longitudinal Study of Ageing (ELSA)

Background The aim was to investigate the association between sleep disturbances and cognitive function in younger and older individuals from an ageing population. Methods 3,968 male and 4,821 female white participants, aged 50 years and over, from the English Longitudinal Study of Ageing (ELSA) were studied. Information on sleep quality and quantity as well as both amnestic (memory, ACF) and non-amnestic (non-memory, nACF) function was available at Wave 4 (2008). Analysis of covariance was used to evaluate the relationship between sleep and cognitive function. Results After adjustment for multiple confounders in the younger group (50–64 years) duration of sleep explained 15.2% of the variance in ACF (p = 0.003) and 20.6% of nACF (p = 0.010). In the older group (65+ years) the estimates were 21.3% (p<0.001) and 25.6% (p<0.001), respectively. For sleep quality, there was a statistically significant association between sleep quality and both ACF (p<0.001) and nACF (p<0.001) in the older age group, but not in the younger age group (p = 0.586 and p = 0.373, respectively; interaction between age and sleep quality in the study sample including both age groups: p<0.001 for ACF and p = 0.018 for nACF). Sleep quality explained between 15.1% and 25.5% of the variance in cognition. The interaction with age was independent of duration of sleep. At any level of sleep duration there was a steeper association between sleep quality and ACF in the older than the younger group. Conclusions The associations between sleep disturbances and cognitive function vary between younger and older adults. Prospective studies will determine the temporal relationships between sleep disturbances and changes in cognition in different age groups

Body size in early life and risk of epithelial ovarian cancer: results from the Nurses' Health Studies

Adult body mass index (BMI) has been associated with ovarian cancer risk, but few studies have examined body size earlier in life. We prospectively examined associations of body fatness at ages 5 and 10, BMI at age 18, height, and birthweight with risk of epithelial ovarian cancer in the Nurses' Health Study (NHS: 110 311 women, 735 cases) and Nurses' Health Study II (NHSII: 113 059 women, 137 cases). Cox proportional hazards regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). There was a weak inverse association between average body fatness at ages 5 and 10 and risk in the NHS (RR for heaviest vs most lean=0.81, 95% CI: 0.53–1.24, P for trend=0.04) and a nonsignificant positive association in the NHSII (RR=2.09, 95% CI: 0.98–4.48, P for trend=0.10), possibly due to differences in age and menopausal status. Height was positively associated with risk in both cohorts (RR for ⩾1.75 vs <1.6 m=1.43, 95% CI: 1.05–1.96, P for trend=0.001). Body mass index at the age of 18 years and birthweight were not associated with risk. Further research should examine the biological mechanisms underlying the observed associations

The risk for breast cancer is not evidently increased in women with hyperprolactinemia

The question has been raised whether hyperprolactinemia in humans is associated with an excess risk for breast cancer. We aimed to assess the risk of breast cancer in a previously defined large cohort of patients treated for idiopathic hyperprolactinemia or prolactinomas. Based on the pattern of drug prescriptions we identified 11,314 subjects in the PHARMO network with at least one dispensing of dopamine agonists between 1996 and 2006. Of these, 1,607 subjects were considered to have dopamine agonist—treated hyperprolactinemia based on the prescribing pattern. For the present analysis, we included only women (n = 1,342). Patients with breast cancer were identified by hospital discharge codes. Data on breast cancer incidence in the Netherlands were derived from the Dutch cancer registry. Standardized mortality ratio (SMR) was the measure of outcome to assess the association between hyperprolactinemia and breast cancer. The 1,342 patients accounted for a total of 6,576 person years. Eight patients with breast cancer during follow-up were identified. Indirect standardization with incidence proportions from the general Dutch population revealed a 7.47 expected cases. The calculated SMR for breast cancer risk in patients treated hyperprolactinemia was 1.07 (95% confidence interval 0.50–2.03). In conclusion, there is no clear evidence for increased breast cancer risk in female patients treated for either idiopathic hyperprolactinemia or prolactinomas. The uncertainty about the exact risk that is due to the relatively low number of breast cancer cases, should be overcome by pooling results in a future meta-analysis

Mammographic density and risk of breast cancer by age and tumor characteristics

Introduction: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models. Methods: Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (51%) versus average density (11-25%). Women ages 2.1 cm) versus small tumors and positive versus negative lymph node status (P’s < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55–64 and ≥65 years (Page-interaction = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group. Conclusion: MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization

Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium

10.1186/bcr3381Breast Cancer Research15