Differences in risk factors for breast cancer molecular subtypes in a population-based study.

Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor alpha, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; P(heterogeneity) = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; P(heterogeneity) = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer.     

Correlates of total physical activity among middle-aged and elderly women

Information on correlates of total physical activity (PA) levels among middle-aged and elderly women is limited. This article aims to investigate whether total daily PA levels are associated with age, body mass index, smoking, drinking status, and sociodemographic factors.     

Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) in E{micro}-pim-1 transgenic mice

The usefulness of transgenic Eµ-pim-1 mice over-expressingthe pim-1 oncogene in lymphoid tissues, as sensitive test organismswas studied in a short-term carcinogenicity study. The micewere fed standard diet Altromin 1314 supplemented either with0.03% 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)for 7 months or with 0.03% 2-amino-3-methylimidazo[4, 5-f] quinoline(IQ) for 6 months. PhIP and IQ are heterocyclic amines formedduring cooking of meat and fish and are mutagenic to bacteriaand cultured mammalian cells. PhIP is a potent mouse lymphomagen,while IQ is a liver carcinogen and also causes lung tumors andtumors of the forestomach in mice. We found that transgenicEµ-pim-1 mice are highly susceptible to PhIP induced lymphomagenesisbut do not respond to the IQ treatment. PhIP feeding of Eµ-pim-1mice not only increased the total number of T-cell lymphomasbut also decreased the latency time compared to either transgenicor wild-type controls. The effect was most pronounced in thetreated female Eµ-pim-1 mice, which showed a higher incidenceof PhIP induced T-cell lymphomas than transgenic males and astrongly reduced latency period after PhIP treatment comparedto non-transgenic mice. Our results suggest that the transgenicEµ-pim-1 mouse may be a useful model for short-term carcinogenicityscreening of potential genotoxic carcinogens having the lymphoidsystem as target tissue. The carcinogen IQ which does not havethe lymphoid system as a target was not recognized in this model.     

Influence of water extracts from the surface of two yew (Taxus) species on mites (Tetranychus urticae)

Taxus cuspidata and Taxus media var. Hicksii contain paclitaxel, among other taxoids, on the surface of the needles. These compounds were removed by 5-s dipping of the needles in water just below its boiling point at 96 degrees C and at 60 degrees C and 40 degrees C. Taxus cuspidata contained a fourfold higher concentration of paclitaxel than Taxus media var. Hicksii. The extract with the higher concentration of paclitaxel was more harmful to the mites Tetranychus urticae Koch, increasing their mortality 150%, prolonging development by ca. 20% and lowering the average fecundity from 112 in the control to 16.13 after treatment with Taxus cuspidata; also, the net reproductive rate dropped from 70.24 to 6.70, which is more than a tenfold reduction.     

Drug evolution: p-aminobenzoic acid as a building block

The core or the building block is an important component in drug development. In this article, we propose and review p-aminobenzoic acid (PABA) as a building block used in the design of drugs or drug candidates. PABA is frequently found as a structure moiety in drugs. For example, in a database of 12,111 commercial drugs, 1.5% (184 drugs) were found to contain the PABA moiety. These drugs have a wide range of therapeutic uses, such as: sun-screening, antibacterial, antineoplastic, local anesthetic, anticonvulsant, anti-arrhythmic, anti-emetic, gastrokinetic, antipsychotic, neuroleptic, and migraine prophylactic. This article reviews the molecular targets and the mechanisms of these activities. Drugs containing PABA also show a wide range of structural diversity. Of the 184 PABA containing drugs identified, 95 different substitutions were found at the carboxylic group and 61 were found at the amino group of the building block. Substitution on the aromatic ring was also diverse. 13, 3, and 13 different side chains were found to modify positions 2, 3 and 5 of the aromatic ring respectively. In some drugs, the amino group is further substituted to form tertiary amine (4 different side chains). Substitutions at the carboxyl and amino groups of PABA are particularly suitable for the generation of combinatorial libraries. Just by reshuffling the identified side chains of the 184 PABA containing drugs, 4.5 million compounds can be generated. Consequently, PABA fits well as a building block for a general chemical library of "drug-like" molecules with a wide range of functional and structural diversity.     

Catheter induced septicaemia

The most serious catheter-related infections, such as septicaemia are associated with the central venous catheters rather than the peripheral catheters. The main sources of microorganisms are the patient's skin and hospital environment. Bacteria can gain access to blood via the external or the internal catheter surfaces. A number of approaches for the prevention of sepsis associated with catheters have been proposed, with limited success. Beside the careful aseptic techniques, the development of antibacterial polymers offers the greatest potential for further reduction of risk of catheter-related sepsis. However, there is evidence suggesting that an appropriate training of staff in the management and care of catheters is fundamental to achieve a reduction in the incidence of catheter-related infections.     

Fish consumption and breast cancer risk

The omega-3 fatty acids, especially long-chain eicosapentaenoic acid (20:5n-3) and docosahexaenoic (22:6n-3) contained in "fatty" fish, have consistently been shown to retard the growth of breast cancer in vitro and in animal experiments. In contrast, studies of the association between fish consumption and breast cancer risk in human populations have not consistently shown inverse associations. However, previous studies have not considered the specific types of fish consumed. Using data from a large, nationwide case-control study conducted in Sweden, we examined the association between consumption of fatty and lean fish and breast cancer risk. Odds ratios (OR) and 95% confidence intervals were computed from unconditional logistic regression models. High consumption of fish was weakly associated with reduced breast cancer risk, and the association was not statistically significant. With multivariate adjustment, the OR for women with the highest consumption (> or =3.5 servings/wk) compared with women with the lowest (virtually none) was 0.88 (95% confidence interval = 0.60-1.29, P for trend = 0.15). When type of fish was examined separately, the association was similar for fatty and lean fish.     

Dietary calcium and vitamin D intake and risk of colorectal cancer: a prospective cohort study in women

Although laboratory data and a few adenoma prevention trials suggest that calcium supplementation may reduce the risk of colorectal neoplasia, the results of observational studies of calcium intake and colorectal cancer risk are contradictory. However, few studies have examined the association among women or effects in specific colon subsites. Women with colorectal cancer diagnosed through 31 December 2000 were identified by linkage to regional cancer registries. During an average 11.3 yr of follow-up of 61,463 women, we observed 572 incident cases of colorectal cancer. Using data obtained from a 67-item food frequency questionnaire and Cox proportional hazards models to estimate rate ratios and 95% confidence intervals, we found an inverse association between dietary calcium intake and colorectal cancer risk. Women with the highest calcium intake (median 914 mg/day) had a reduced risk of colorectal cancer (rate ratio = 0.72, 95% confidence interval = 0.056-0.93, P for trend = 0.02) compared with women with the lowest intake (median 486 mg/day). Furthermore, our results suggest that the inverse association may be strongest in relation to distal cancers and among older women. The association with dairy products was less clear, suggesting that calcium intake per se is more important than specific calcium sources. Vitamin D intake was not clearly associated with risk. In sum, our data suggest that high calcium intake may lower colorectal cancer risk.     

Dietary factors in relation to endometrial cancer: a nationwide case-control study in Sweden

The incidence of endometrial cancer varies up to 10-fold between high- and low-incidence regions, suggesting the importance of environmental factors, including diet, in the etiology of this disease. However, few studies have examined the role of diet in the etiology of endometrial cancer. Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we analyzed data from a large, case-control study of Swedish-born postmenopausal women aged 50-74 yr (709 cases and 2,887 controls) residing in Sweden between 1994 and 1995. We found no clear association between foods or food groups and endometrial cancer risk, although high consumption of certain foods, such as Brassica vegetables, coffee, and legumes, might be associated with small-to-moderate reduced risks of endometrial cancer, while red meat consumption might be associated with a small-to-moderate increased risk. Daily use of calcium supplements appeared to lower endometrial cancer risk (OR = 0.5, 95% CI = 0.3-0.9, P for trend = 0.04), especially among women with low calcium intake from dairy products. On the other hand, the use of iron supplements appeared to increase the risk (OR = 1.7, 95% CI = 0.9-3.3, P for trend = 0.03). The findings are discussed with respect to previous studies and the possible underlying mechanisms.