Mammographic density and epithelial histopathologic markers

<p>Abstract</p> <p>Background</p> <p>We explored the association of mammographic density, a breast cancer risk factor, with hormonal and proliferation markers in benign tissue from tumor blocks of pre-and postmenopausal breast cancer cases.</p> <p>Methods</p> <p>Breast cancer cases were recruited from a case-control study on breast density. Mammographic density was assessed on digitized prediagnostic mammograms using a computer-assisted method. For 279 participants of the original study, we obtained tumor blocks and prepared tissue microarrays (TMA), but benign tissue cores were only available for 159 women. The TMAs were immunostained for estrogen receptor alpha (ERα) and beta (ERβ), progesterone receptor (PR), HER2/neu, Ki-67, and Proliferating Cell Nuclear Antigen (PCNA). We applied general linear models to compute breast density according to marker expression.</p> <p>Results</p> <p>A substantial proportion of the samples were in the low or no staining categories. None of the results was statistically significant, but women with PR and ERβ staining had 3.4% and 2.4% higher percent density. The respective values for Caucasians were 5.7% and 11.6% but less in Japanese women (3.5% and -1.1%). Percent density was 3.4% higher in women with any Ki-67 staining and 2.2% in those with positive PCNA staining.</p> <p>Conclusion</p> <p>This study detected little evidence for an association between mammographic density and expression of steroid receptors and proliferation markers in breast tissue, but it illustrated the problems of locating tumor blocks and benign breast tissue samples for epidemiologic research. Given the suggestive findings, future studies examining estrogen effects in tissue, cell proliferation, and density in the breast may be informative.</p

Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers

Abstract Introduction Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies. Methods We successfully genotyped 24 SNPs in a cohort of up to 4,724 BRCA1 and 2,693 BRCA2 female mutation carriers from 15 study groups and assessed whether these variants were associated with risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Results SNPs in five of the 14 candidate genes showed evidence of association with breast cancer risk for BRCA1 or BRCA2 carriers (P &lt; 0.05). Notably, the minor alleles of two SNPs (rs7166081 and rs3825977) in high linkage disequilibrium (r 2 = 0.77), located at the SMAD3 locus (15q22), were each associated with increased breast cancer risk for BRCA2 mutation carriers (relative risk = 1.25, 95% confidence interval = 1.07 to 1.45, P trend = 0.004; and relative risk = 1.20, 95% confidence interval = 1.03 to 1.40, P trend = 0.018). Conclusions This study provides evidence that the SMAD3 gene, which encodes a key regulatory protein in the transforming growth factor beta signalling pathway and is known to interact directly with BRCA2, may contribute to increased risk of breast cancer in BRCA2 mutation carriers. This finding suggests that genes with expression associated with BRCA1 and BRCA2 mutation status are enriched for the presence of common genetic modifiers of breast cancer risk in these populations

Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers : results from the Consortium of Investigators of Modifiers of BRCA1/2.

Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 &#215; 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers

Pure fruit juice and fruit consumption and the risk of CVD: the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study.

Dietary guidelines for pure fruit juice consumption differ between countries, regarding the question whether pure fruit juice is an acceptable alternative for fruit. Currently, little is known about pure fruit juice consumption and the risk of CVD. In this prospective cohort study, we studied the association of pure fruit juice and fruit consumption with the incidence of fatal and non-fatal CVD, CHD and stroke and investigated the differences in association with pure fruit juice consumption between low and high fruit consumers. A validated FFQ was used to estimate dietary intake of 34 560 participants (26·0 % men and 74·0 % women) aged 20-69 years from the European Prospective Investigation into Cancer and Nutrition-Netherlands study. Adjusted hazard ratios (HR) were estimated using Cox regression after average follow-up of 14·6 years. Compared with no consumption, pure fruit juice consumption up to 7 glasses/week - but not consumption of ≥8 glasses - was significantly associated with reduced risk of CVD and CHD, with HR from 0·83 (95 % CI 0·73, 0·95) to 0·88 (95 % CI 0·80, 0·97). Consumption of 1-4 and 4-8 glasses/week was significantly associated with lower risk of stroke with HR of 0·80 (95 % CI 0·64, 0·99) and 0·76 (95 % CI 0·61, 0·94), respectively. Associations did not differ considerably between low and high fruit consumers. The highest three quintiles of fruit consumption (≥121 g/d) were significantly associated with lower incidence of CVD, with HR of 0·87 (95 % CI 0·78, 0·97) and 0·88 (95 % CI 0·80, 0·98). In conclusion, although we observed favourable associations of moderate pure fruit juice consumption with CVD, for now consumption of whole fruit should be preferred because the evidence of the health benefits of fruit is more conclusive

Pure fruit juice and fruit consumption and the risk of CVD: the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study.

Dietary guidelines for pure fruit juice consumption differ between countries, regarding the question whether pure fruit juice is an acceptable alternative for fruit. Currently, little is known about pure fruit juice consumption and the risk of CVD. In this prospective cohort study, we studied the association of pure fruit juice and fruit consumption with the incidence of fatal and non-fatal CVD, CHD and stroke and investigated the differences in association with pure fruit juice consumption between low and high fruit consumers. A validated FFQ was used to estimate dietary intake of 34 560 participants (26·0 % men and 74·0 % women) aged 20-69 years from the European Prospective Investigation into Cancer and Nutrition-Netherlands study. Adjusted hazard ratios (HR) were estimated using Cox regression after average follow-up of 14·6 years. Compared with no consumption, pure fruit juice consumption up to 7 glasses/week - but not consumption of ≥8 glasses - was significantly associated with reduced risk of CVD and CHD, with HR from 0·83 (95 % CI 0·73, 0·95) to 0·88 (95 % CI 0·80, 0·97). Consumption of 1-4 and 4-8 glasses/week was significantly associated with lower risk of stroke with HR of 0·80 (95 % CI 0·64, 0·99) and 0·76 (95 % CI 0·61, 0·94), respectively. Associations did not differ considerably between low and high fruit consumers. The highest three quintiles of fruit consumption (≥121 g/d) were significantly associated with lower incidence of CVD, with HR of 0·87 (95 % CI 0·78, 0·97) and 0·88 (95 % CI 0·80, 0·98). In conclusion, although we observed favourable associations of moderate pure fruit juice consumption with CVD, for now consumption of whole fruit should be preferred because the evidence of the health benefits of fruit is more conclusive

Presentazione di "Agostino e il destino dell’Occidente"

Background: The relatively high dietary intake of soy in Asian countries has been hypothesized to, at least partly, explain the lower breast cancer incidence patterns in these countries compared with the Western world. The aim of the present study was to determine the effect of daily soy supplementation on mammographic density, one of the strongest known risk factors for breast cancer. Methods: A double-blind, randomized, controlled trial was conducted to compare the effects of soy protein intake containing 99 mg isoflavones daily with intake of milk protein (placebo) for the duration of 1 year. Two hundred and two Dutch postmenopausal women ages 60 to 75 years were randomized. Mammographic density was assessed using a quantitative computer-assisted method on digitized mammograms. Equol producer status was assessed in plasma provided at the final visit (soy group) or after a 3-day challenge with soy after the trial was finished (placebo group). Results: A total of 175 women completed the baseline visits and at least one follow-up visit and were included in the intention-to-treat analyses. For 126 women, both pre- and post-trial mammograms were available. Marmnographic density decreased in both study arms, but the decrease did not differ significantly between intervention and placebo groups. Equol producer status did not modify the results. Conclusion: The results of this trial do not support the hypothesis that a diet high in soy protein among postmenopausal women decreases mammographic density