Birth weight and mammographic density among postmenopausal women in Sweden

Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population‐based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio‐lateral oblique view were digitized and the Cumulus software was used for computer‐assisted semi‐automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001–3500 grams at birth, women with birth weights >4000g were at almost 3‐fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.     

The epidemiology of cataract: a study in Greece

Purpose: We conducted a case–control study to identify risk factors for cataract in the Mediterranean Greek population. Three hundred and fourteen cases and 314 frequency‐matched controls of both genders, aged 45–85, attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study. Methods: Cases were medically diagnosed and classified. Controls were healthy visitors without cataract. A detailed questionnaire, covering demographic, socioeconomic, somatometric, lifestyle and medical history variables, provided data on possible risk factors for cataract. Analyses were conducted through multiple logistic regression. Main outcome measures: Cataract overall and by type: nuclear, cortical and posterior subcapsular (PSC). Results: Statistically significant increased risk for cataract overall was found for current (OR = 1.99, 95%CI: 1.23–3.23) and ex‐smokers (OR = 1.64, 95%CI: 1.02–2.70), history of coronary heart disease (OR = 2.25, 95%CI: 1.43–3.55), family history of ophthalmologic diseases (OR = 1.51, 95%CI: 1.03–2.20) and higher sunlight exposure at the beach (OR = 2.26, 95%CI: 1.37–3.72) as well as at work (OR = 2.03, 95%CI: 1.32–3.12). Use of measures protecting against sunlight at the beach, i.e. hat (OR = 0.58, 95%CI: 0.39–0.85) and vision repair spectacles (OR = 0.44, 95%CI: 0.30–0.65), were associated with reduced risk. Results for cataract overall were also evident for the nuclear type and in most circumstances for PSC type, but were only suggestive for the cortical type of cataract. Conclusion: We identified certain possible risk factors for age‐related cataract. In a Mediterranean Greek population, we found that smoking, use of cortisone drops, cardiovascular heart disease and sunlight exposure increase the risk for cataract, while use of hat and vision repair spectacles act protectively.     

Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk

Estrogens play a central role in the etiology of breast cancer, and results from observational studies and randomized trials have also implicated progestins. The effects of these hormones in the mammary tissue are exerted through binding with specific receptor proteins in the cell nucleus. It has been proposed that higher estrogen receptor alpha expression in the normal breast epithelium may increase breast cancer risk. In a study in Greece, we determined estrogen alpha and progesterone receptor expression in normal mammary tissue adjacent to the pathological tissue from 267 women with breast cancer and 299 women with benign breast disease. Mouse monoclonal antibodies specific for estrogen receptor alpha and progesterone receptor were applied. The H-index, which incorporates frequency and intensity of staining of the cells, and can range from 0 to 300, was deemed positive when it exceeded 9. Among premenopausal women, there was no evidence for an association with breast cancer risk for expression of either type of receptors. Among postmenopausal women, breast cancer risk was inversely associated with expression of both estrogen alpha (odds ratio (OR)=0.39; p=0.015) and progesterone (OR=0.40; p=0.008) receptors. The hypothesis that overexpression of estrogen receptors alpha or progesterone receptors in normal breast epithelium may increase the risk of breast cancer was not supported by our data. Instead, we found evidence that overexpression of these receptors may be associated with reduced risk for breast cancer in line with the well-known association of expression of these receptors in the malignant tissue and better breast cancer prognosis.     

Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: A nested case‐control study in nonsmoking postmenopausal women from the EPIC cohort

Acrylamide, classified in 1994 by IARC as “probably carcinogenic to humans,” was discovered in 2002 in some heat‐treated, carbohydrate‐rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case‐control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non‐smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type‐I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HR_HbAA;Q5vsQ1: 0.84, 95%CI: 0.49–1.48; HR_HbGA;Q5vsQ1: 0.94, 95%CI: 0.54–1.63) or type‐I EC risk. Additionally, none of the subgroups investigated (BMI < 25 vs. ≥25 kg m^?2, alcohol drinkers vs. never drinkers, oral contraceptive users vs. non‐users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type‐I EC risk in 768 nonsmoking postmenopausal women from the EPIC cohort.     

Dietary total antioxidant capacity in relation to endometrial cancer risk: a case–control study in Italy

Purpose

To investigate the role of the overall antioxidant activity of diet, we estimated the relation between three dietary indices of total antioxidant capacity (TAC) and endometrial cancer risk

Methods

We analyzed data from an Italian case–control study including 454 women with incident, histologically confirmed endometrial cancer, and 908 frequency-matched controls admitted to the same hospitals as cases for acute non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects’ habitual diet. TAC was measured using Italian food composition tables in terms of Ferric-reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and total radical-trapping antioxidant parameter (TRAP). We computed odds ratios (OR) and corresponding 95 % confidence intervals (CIs) using conditional multiple logistic regression models, including terms for recognized endometrial cancer risk factors and total energy intake.

Results

TAC was inversely related to endometrial cancer risk with ORs for the highest versus the lowest quartile of 0.69 (95 % CI 0.47–1.00) for FRAP, 0.68 (95 % CI 0.46–0.99) for TEAC, and 0.68 (95 % CI 0.47–0.98) for TRAP. The relations appeared consistent in strata of selected risk factors and decreased when considering TAC without the contribution of coffee.

Conclusions

Our findings suggest a favorable role of a diet high in TAC on endometrial cancer risk, which can be partially driven by coffee consumption.

     

Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological sub-type and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC.     

Early life diet and the risk for adult breast cancer

A hypothesis postulating intrauterine and early life influences on the occurrence of breast cancer in adult life has received considerable support in the literature. We present alternative or complementary ways through which diet could affect breast cancer risk in this context. Emphasis is placed on evidence that reduced energy intake in early life is associated with smaller body size, which, in turn, constrains birth weight and subsequent development of offspring and is associated with reduced breast cancer risk.     

Facilitating informed decision making about breast cancer risk and genetic counseling among women calling the NCI's Cancer Information Service

Despite increased interest among the public in breast cancer genetic risk and genetic testing, there are limited services to help women make informed decisions about genetic testing. This study, conducted with female callers (N = 279) to the National Cancer Institute's (NCI's) Atlantic Region Cancer Information Service (CIS), developed and evaluated a theory-based, educational intervention designed to increase callers' understanding of the following: (a) the kinds of information required to determine inherited risk; (b) their own personal family history of cancer; and (c) the benefits and limitations of genetic testing. Callers requesting information about breast/ovarian cancer risk, risk assessment services, and genetic testing were randomized to either: (1) standard care or (2) an educational intervention. Results show that the educational intervention reduced intention to obtain genetic testing among women at average risk and increased intention among high-risk women at 6 months. In addition, high monitors, who typically attend to and seek information, demonstrated greater increases in knowledge and perceived risk over the 6-month interval than low monitors, who typically are distracted from information. These findings suggest that theoretically designed interventions can be effective in helping women understand their cancer risk and appropriate risk assessment options and can be implemented successfully within a service program like the CIS.     

Carbon nanotubes: materials for medicinal chemistry and biotechnological applications

Carbon nanotubes are considered as molecular wires exhibiting novel properties for diverse applications including medicinal and biotechnological purposes. Surface chemistry on carbon nanotubes results on their solubilization in organic solvents and/or aqueous/physiological media. Herein, we will present how interfacing such novel carbon-based nanomaterials with biological systems may lead to new applications in diagnostics, vaccine and drug delivery. Recent developments in this rapidly growing field will be presented thus suggesting exciting opportunities for the utilization of carbon nanotubes as useful tools for biotechnological applications. Emphasis will be placed in the integration of biomaterials with carbon nanotubes, which enables the use of such hybrid systems as biosensor devices, immunosensors and DNA-sensors.