An elevated PSA, which normalizes, does not exclude the presence of prostate cancer

The purpose of this study was to determine the incidence of prostate cancer in patients who have an elevated referral prostate-specific antigen (PSA), which subsequently falls to within their normal age-specific reference range prior to prostate biopsy. The study demonstrated that of the 160 patients recruited, 21 (13%) had a repeat PSA level which had fallen back to within their normal range. Five of these 21 patients (24%) were diagnosed with prostate cancer following biopsy, two of whom had a benign prostate examination. The study, therefore, demonstrates that normalisation of the PSA level prior to biopsy does not exclude the presence of prostate cancer even when the prostate feels benign.

Recorded quadrant incidence of female breast cancer in Great Britain suggests a disproportionate increase in the upper outer quadrant of the breast

Background: The upper outer quadrant (UOQ) of the breast is the most frequent site for incidence of breast cancel; but the reported disproportionate incidence in this quadrant appears to rise with year of publication. Materials and Methods: In order to determine whether this increasing incidence in the UOQ is an artifact of different study populations or is chronological, data have been analysed for annual quadrant incidence of female breast cancer recorded nationally in England and Wales between 1979 and 2000 and in Scotland between 1980 and 2001. Results: In England and Wales, the recorded incidence of female breast cancer in the UOQ rose front 47.9% in 1979 to 53.3% in 2000, and has done so linearly over tune with a con-elation coefficient R of +/- 0.71 +/- SD 0.01 (p < 0.001). Analysis of independent data front Scotland showed a similar trend in that recorded female breast cancer had also increased in the UOQ from 38.3% in 1980 to 54.7% in 2001, with a con-elation coefficient R for the linear annual increase of +0.80 +/- SD 0.03 (p < 0.001). Conclusion: These results are inconsistent with current views that the high level of UOQ breast cancer is due solely to a greater amount of target epithelial tissue in that region. Identification of the reasons for such a disproportionate site-specific increase could provide clues as to causative factors in breast cancer.

Endocrine disrupters and human health: Could oestrogenic chemicals in body care cosmetics adversely affect breast cancer incidence in women? A review of evidence and call for further research

In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected in human breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of. data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, because exposure to oestrogenic chemicals through application of body care products (unlike diffuse environmental chemical exposures) should be amenable to evaluation, quantification and control. The exposure issues are clear and the exposed population is large, and these factors should provide the necessary impetus to investigate this potential issue of public health. Copyright (C) 2004 John Wiley Sons, Ltd.

Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17 beta-oestradiol in MCF7 human breast cancer cells

Since the alkyl esters of p-hydroxybenzoic acid (parabens) can be measured intact in the human breast and possess oestrogenic properties, it has been suggested that they could contribute to an aberrant burden of oestrogen signalling in the human breast and so play a role in the rising incidence of breast cancer. However, although parabens have been shown to regulate a few single genes (reporter genes, pS2, progesterone receptor) in a manner similar to that of 17 beta-oestradiol, the question remains as to the full extent of the similarity in the overall gene profile induced in response to parabens compared with 17 beta-oestradiol. The GE-Amersham CodeLink 20 K human expression microarray system was used to profile the expression of 19881 genes in MCF7 human breast cancer cells following a 7-day exposure to 5 x 10(-4) m methylparaben, 10(-5) m n-butylparaben and 10(-8) m 17 beta-oestradiol. At these concentrations, the parabens gave growth responses in MCF7 cells of similar magnitude to 17 beta-oestradiol. The study identified genes which are upregulated or downregulated to a similar extent by methylparaben, n-butylparaben and 17 beta-oestradiol. However, the majority of genes were not regulated in the same way by all three treatments. Some genes responded differently to parabens from 17 beta-oestradiol, and furthermore, differences in expression of some genes could be detected even between the two individual parabens. Therefore, although parabens possess oestrogenic properties, their mimicry in terms of global gene expression patterns is not perfect and differences in gene expression profiles could result in consequences to the cells that are not identical to those following exposure to 17 beta-oestradiol. Copyright (c) 2006 John Wiley & Sons, Ltd.

Environmental oestrogens and breast cancer: evidence for combined involvement of dietary, household and cosmetic xenoestrogens

Many environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied. CONCLUSION: If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.

Components of olive oil and chemoprevention of colorectal cancer

Olive oil contains a vast range of substances such as monounsaturated free fatty acids (e.g., oleic acid), hydrocarbon squalene, tocopherols, aroma components, and phenolic compounds. Higher consumption of olive oil is considered the hallmark of the traditional Mediterranean diet, which has been associated with low incidence and prevalence of cancer, including colorectal cancer. The anticancer properties of olive oil have been attributed to its high levels of monounsaturated fatty acids, squalene, tocopherols, and phenolic compounds. Nevertheless, there is a growing interest in studying the role of olive oil phenolics in carcinogenesis. This review aims to provide an overview of the relationship between olive oil phenolics and colorectal cancer, in particular summarizing the epidemiologic, in vitro, cellular, and animal studies on antioxidant and anticarcinogenic effects of olive oil phenolics.

Role of mammalian lignans in the prevention and treatment of prostate cancer

Prostate cancer is poised to become the most prevalent male cancer in the Western world. In Japan and China, incidence rates are almost 10-fold less those reported in the United States and the European Union. Epidemiological data suggest that environmental factors such as diet can significantly influence the incidence and mortality of prostate cancer. The differences in lifestyle between East and West are one of the major risk factors for developing prostate cancer. Traditional Japanese and Chinese diets are rich in foods containing phytoestrogenic compounds, whereas the Western diet is a poor source of these phytochemicals. The lignan phytoestrogens are the most widely occurring of these compounds. In vitro and in vivo reports in the literature indicate that lignans have the capacity to affect the pathogenesis of prostate cancer. However, their precise mechanism of action in prostate carcinogenesis remains unclear. This article outlines the possible role of lignans in prostate cancer by reviewing the current in vitro and in vivo evidence for their anticancer activities. The intriguing concept that lignans may play a role in the prevention and treatment of prostate cancer over the lifetime of an individual is discussed.

Environmental oestrogens and breast cancer: long-term low-dose effects of mixtures of various chemical combinations

The incidence of breast cancer has risen worldwide to unprecedented levels in recent decades, making it now the major cancer of women in many parts of the world.1 Although diet, alcohol, radiation and inherited loss of BRCA1/2 genes have all been associated with increased incidence, the main identified risk factors are life exposure to hormones including physiological variations associated with puberty/pregnancy/menopause,1 personal choice of use of hormonal contraceptives2 and/or hormone replacement therapy.3–6 On this basis, exposure of the human breast to the many environmental pollutant chemicals capable of mimicking or interfering with oestrogen action7 should also be of concern.8 Hundreds of such environmental chemicals have now been measured in human breast tissue from a range of dietary and domestic exposure sources7 ,9 including persistent organochlorine pollutants (POPs),10 polybrominated diphenylethers and polybromobiphenyls,11 polychlorinated biphenyls,12 dioxins,13 alkyl phenols,14 bisphenol-A and chlorinated derivatives,15 as well as other less lipophilic compounds such as parabens (alkyl esters of p-hydroxybenzoic acid),16 but studies investigating any association between raised levels of such compounds and the development of breast cancer remain inconclusive.7–16 However, the functionality of these chemicals has continued to be assessed on the basis of individual chemicals rather than the environmental reality of long-term low-dose exposure to complex mixtures. This misses the potential for individuals to have high concentrations of different compounds but with a common mechanism of action. It also misses the complex interactions between chemicals and physiological hormones which together may act to alter the internal homeostasis of the oestrogenic environment of mammary tissue.

Diallyl disulfide-induced apoptosis in a breast-cancer cell line (MCF-7) may be caused by inhibition of histone de-acetylation

The health benefits of garlic have been proven by epidemiological and experimental studies. Diallyl disulphide (DADS), the major organosulfur compound found in garlic oil, is known to lower the incidence of breast cancer both in vitro and in vivo. The studies reported here demonstrate that DADS induces apoptosis in the MCF-7 breast-cancer cell line through interfering with cell-cycle growth phases in a way that increases the sub-G0 population and substantially halts DNA synthesis. DADS also induces phosphatidylserine (PS) translocation from the inner to the outer leaflet of the plasma membrane and activates caspase-3. Further studies revealed that DADS modulates the cellular levels of Bax, Bcl-2, Bcl-xL and Bcl-w in a dose-dependent manner, suggesting the involvement of Bcl-2 family proteins in DADS induced apoptosis. Histone deacetylation inhibitors (HDACi) are known to suppress cancer growth and induce apoptosis in cancer cells. Here it is shown that DADS has HDACi properties in MCF-7 cells as it lowers the removal of an acetyl group from an acetylated substrate and induces histone-4 (H4) hyper-acetylation. The data thus indicate that the HDACi properties of DADS may be responsible for the induction of apoptosis in breast cancer cells.

Uneven distribution of nutrients in the root zone affects the incidence of blossom end rot and concentration of calcium and potassium in fruits of tomato

Tomato plants ( Lycopersicon esculentum Mill. var. DRK) were grown hydroponically to determine the effect of an uneven distribution of nutrients in the root zone on blossomend rot (BER) and Ca and K concentrations in the fruits. The plants were grown in rockwool with their root system divided into two portions. Each portion was irrigated with nutrient solutions with either the same or the different electrical conductivity (EC) in the range 0 to 6 dS m(-1). Solutions with high EC supplied to both sides of the root system significantly increased the incidence of BER. However, when only water or a solution of low EC was supplied to one portion, BER was reduced by 80%. Fruit yields were significantly higher ( P < 0.01) for plants that received solutions of the uneven EC treatments (6/0 or 4.5/0 EC treatment). Plants supplied with solutions of uneven EC generally had higher leaf and fruit concentrations of Ca but lower concentrations of K than those supplied with solutions of high EC. There was no difference in Ca concentration at the distal end of young fruits of the uneven EC treatment but it was reduced in the high EC treatments. The concentration of K in the mature fruits of the uneven EC treatments was lower than that of the high EC treatments and higher or similar that of the 3/3 or 2.5/2.5 EC treatments ( controls). A clear relationship was found between the incidence of BER and the exudation rate. High rate of xylem exudation was observed in the uneven EC treatments. Reduction of BER in the uneven EC treatments is most likely to be the effect of high exudation rate on Ca status in the young fruits. It was concluded that high EC of solution had positive effects on Ca concentration and incidence of BER provided that nutrient solution with low EC or water is supplied to the one portion of the root system.

Environmental oestrogens, cosmetics and breast cancer

The established role of oestrogen in the development and progression of breast cancer raises questions concerning a potential contribution from the many chemicals in the environment which can enter the human breast and which have oestrogenic activity. A range of organochlorine pesticides and polychlorinated bipheryls possess oestrogen-mimicking properties and have been measured in human breast adipose tissue and in human milk. These enter the breast from varied environmental contamination of food, water and air, and due to their lipophilic properties can accumulate in breast fat. However, it is emerging that the breast is also exposed to a range of oestrogenic chemicals applied as cosmetics to the underarm and breast area. These cosmetics are left on the skin in the appropriate area, allowing a more direct dermal absorption route for breast exposure to oestrogenic chemicals and allowing absorbed chemicals to escape systemic metabolism. This review considers evidence in support of a functional role for the combined interactions of cosmetic chemicals with environmental oestrogens, pharmacological oestrogens, phyto-oestrogens and physiological oestrogens in the rising incidence of breast cancer.

Aluminium, antiperspirants and breast cancer

Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metal I oestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer. (c) 2005 Elsevier Inc. All rights reserved.

Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies

Objective: To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally Occurring radon gas. Design: Collaborative analysis of individual data from 13 case-control studies of residential radon and lung cancer. Setting Nine European countries. Subjects 7148 cases Of lung cancer and 14 208 controls. Main outcome measures: Relative risks of lung cancer and radon gas concentrations in homes inhabited during the previous 5-34 years measured in becquerels (radon disintegrations per second) per cubic incite (Bq/m(3)) Of household air. Results: The mean measured radon concentration in homes of people in tire control group was 97 Bq/m(3), with 11% measuring > 200 and 4% measuring > 400 Bq/m(3). For cases of lung cancer the mean concentration was 104 Bq/m(3). The risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%) per 100 Bq/m(3) increase in measured radon (P = 0.0007). This corresponds to an increase of 16% (5% to 31%) per 100 Bq/m(3) increase in usual radon-that is, after correction for the dilution caused by random uncertainties in measuring radon concentrations. The dose-response relation seemed to be linear with no threshold and remained significant (P=0.04) in analyses limited to individuals from homes with measured radon < 200 Bq/m(3). The proportionate excess risk did not differ significantly with study, age, sex, or smoking. In the absence of other causes of death, the absolute risks of lung cancer by age 75 years at usual radon concentrations of 0, 100, and 400 Bq/m(3) would be about 0.4%, 0.5%, and 0.7%, respectively, for lifelong non-smokers, and about 25 times greater (10%, 12%, and 16%) for cigarette smokers. Conclusions: Collectively, though not separately, these studies show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe.

Uneven distribution of nutrients in the root zone affects the incidence of blossom end rot and concentration of calcium and potassium in fruits of tomato

Tomato plants ( Lycopersicon esculentum Mill. var. DRK) were grown hydroponically to determine the effect of an uneven distribution of nutrients in the root zone on blossomend rot (BER) and Ca and K concentrations in the fruits. The plants were grown in rockwool with their root system divided into two portions. Each portion was irrigated with nutrient solutions with either the same or the different electrical conductivity (EC) in the range 0 to 6 dS m(-1). Solutions with high EC supplied to both sides of the root system significantly increased the incidence of BER. However, when only water or a solution of low EC was supplied to one portion, BER was reduced by 80%. Fruit yields were significantly higher ( P < 0.01) for plants that received solutions of the uneven EC treatments (6/0 or 4.5/0 EC treatment). Plants supplied with solutions of uneven EC generally had higher leaf and fruit concentrations of Ca but lower concentrations of K than those supplied with solutions of high EC. There was no difference in Ca concentration at the distal end of young fruits of the uneven EC treatment but it was reduced in the high EC treatments. The concentration of K in the mature fruits of the uneven EC treatments was lower than that of the high EC treatments and higher or similar that of the 3/3 or 2.5/2.5 EC treatments ( controls). A clear relationship was found between the incidence of BER and the exudation rate. High rate of xylem exudation was observed in the uneven EC treatments. Reduction of BER in the uneven EC treatments is most likely to be the effect of high exudation rate on Ca status in the young fruits. It was concluded that high EC of solution had positive effects on Ca concentration and incidence of BER provided that nutrient solution with low EC or water is supplied to the one portion of the root system.