Effects on the immune system associated with living near a pesticide dump site.

In this paper, we report results of the second phase of a larger study designed to evaluate the effects on the immune system of living near a Superfund site containing organochlorine pesticides, volatile organic compounds, and metals. Phase II was conducted to determine whether living near the site, consisting of six locations in Aberdeen, North Carolina, is associated with higher plasma organochlorine levels, immune suppression, or DNA damage. Each of 302 residents of Aberdeen and neighboring communities provided a blood specimen, underwent a skin test, and answered a questionnaire. Blood specimens were analyzed for organochlorine pesticides, immune markers, and micronuclei. Of 20 organochlorines tested, only DDE was detected in the blood of participants (except for one individual). Age-adjusted mean plasma DDE levels were 4.05 ppb for Aberdeen residents and 2.95 ppb (p = 0.01) for residents of neighboring communities. Residents of 40-59 years of age who lived within a mile of any site, but particularly the Farm Chemicals site, had higher plasma DDE levels than residents who lived farther away. Residents who lived near the Farm Chemicals site before versus after 1985 also had higher plasma DDE levels. Overall, there were few differences in immune markers between residents of Aberdeen and the neighboring communities. However, residents who lived closer to the dump sites had statistically significantly lower mitogen-induced lymphoproliferative activity than residents who lived farther away (p < 0.05). Residential location was not consistently associated with frequency of micronuclei or skin test responses. Although some statistically significant differences in immune markers were noted in association with residential location, the magnitude of effects are of uncertain clinical importance

A GIS-based method for household recruitment in a prospective pesticide exposure study

<p>Abstract</p> <p>Background</p> <p>Recent advances in GIS technology and remote sensing have provided new opportunities to collect ecologic data on agricultural pesticide exposure. Many pesticide studies have used historical or records-based data on crops and their associated pesticide applications to estimate exposure by measuring residential proximity to agricultural fields. Very few of these studies collected environmental and biological samples from study participants. One of the reasons for this is the cost of identifying participants who reside near study fields and analyzing samples obtained from them. In this paper, we present a cost-effective, GIS-based method for crop field selection and household recruitment in a prospective pesticide exposure study in a remote location. For the most part, our multi-phased approach was carried out in a research facility, but involved two brief episodes of fieldwork for ground truthing purposes. This method was developed for a larger study designed to examine the validity of indirect pesticide exposure estimates by comparing measured exposures in household dust, water and urine with records-based estimates that use crop location, residential proximity and pesticide application data. The study focused on the pesticide atrazine, a broadleaf herbicide used in corn production and one of the most widely-used pesticides in the U.S.</p> <p>Results</p> <p>We successfully used a combination of remotely-sensed data, GIS-based methods and fieldwork to select study fields and recruit participants in Illinois, a state with high corn production and heavy atrazine use. Our several-step process consisted of the identification of potential study fields and residential areas using aerial photography; verification of crop patterns and land use via site visits; development of a GIS-based algorithm to define recruitment areas around crop fields; acquisition of geocoded household-level data within each recruitment area from a commercial vendor; and confirmation of final participant household locations via ground truthing. The use of these procedures resulted in a sufficient sample of participants from 14 recruitment areas in seven Illinois counties.</p> <p>Conclusion</p> <p>One of the challenges in pesticide research is the identification and recruitment of study participants, which is time consuming and costly, especially when the study site is in a remote location. We have demonstrated how GIS-based processes can be used to recruit participants, increase efficiency and enhance accuracy. The method that we used ultimately made it possible to collect biological samples from a specific demographic group within strictly defined exposure areas, with little advance knowledge of the location or population.</p

A comparison of sunlight exposure in men with prostate cancer and basal cell carcinoma

Ultraviolet radiation exposure increases basal cell carcinoma (BCC) risk, but may be protective against prostate cancer. We attempted to identify exposure patterns that confer reduced prostate cancer risk without increasing that of BCC. We used a questionnaire to assess exposure in 528 prostate cancer patients and 442 men with basal cell carcinoma, using 365 benign prostatic hypertrophy patients as controls. Skin type 1 (odds ratio (OR)=0.47, 95% CI=0.26–0.86), childhood sunburning (OR=0.38, 95% CI=0.26–0.57), occasional/frequent sunbathing (OR=0.21, 95% CI=0.14–0.31), lifetime weekday (OR=0.85, 95% CI=0.80–0.91) and weekend exposure (OR=0.79, 95% CI=0.73–0.86) were associated with reduced prostate cancer risk. Skin type 1 (OR=4.00, 95% CI=2.16–7.41), childhood sunburning (OR=1.91, 95% CI=1.36–2.68), regular foreign holidays (OR=6.91, 95% CI=5.00-9.55) and weekend (OR=1.17, 95% CI=1.08–1.27) but not weekday exposure were linked with increased BCC risk. Combinations of one or two parameters were associated with a progressive decrease in the ORs for prostate cancer risk (OR=0.54–0.25) with correspondingly increased BCC risk (OR=1.60–2.54). Our data do not define exposure patterns that reduce prostate cancer risk without increasing BCC risk

Current opinion on the role of testosterone in the development of prostate cancer: a dynamic model

Background: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven. Presentation of the Hypothesis: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer. Testing of the Hypothesis: Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis. Implications of the Hypothesis: Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy

Inhibitory effects of retinoic acid metabolism blocking agents (RAMBAs) on the growth of human prostate cancer cells and LNCaP prostate tumour xenografts in SCID mice

In recent studies, we have identified several highly potent all-trans-retinoic acid (ATRA) metabolism blocking agents (RAMBAs). On the basis of previous effects of liarozole (a first-generation RAMBA) on the catabolism of ATRA and on growth of rat Dunning R3227G prostate tumours, we assessed the effects of our novel RAMBAs on human prostate tumour (PCA) cell lines. We examined three different PCA cell lines to determine their capacity to induce P450-mediated oxidation of ATRA. Among the three different cell lines, enhanced catabolism was detected in LNCaP, whereas it was not found in PC-3 and DU-145. This catabolism was strongly inhibited by our RAMBAs, the most potent being VN/14-1, VN/50-1, VN/66-1, and VN/69-1 with IC50 values of 6.5, 90.0, 62.5, and 90.0 nM, respectively. The RAMBAs inhibited the growth of LNCaP cells with IC50 values in the μM-range. In LNCaP cell proliferation assays, VN/14-1, VN/50-1, VN/66-1, and VN/69-1 also enhanced by 47-, 60-, 70-, and 65-fold, respectively, the ATRA-mediated antiproliferative activity. We then examined the molecular mechanism underlying the growth inhibitory properties of ATRA alone and in combination with RAMBAs. The mechanism appeared to involve the induction of differentiation, cell-cycle arrest, and induction of apoptosis (TUNEL), involving increase in Bad expression and decrease in Bcl-2 expression. Treatment of LNCaP tumours growing in SCID mice with VN/66-1 and VN/69-1 resulted in modest but statistically significant tumour growth inhibition of 44 and 47%, respectively, while treatment with VN/14-1 was unexpectedly ineffective. These results suggest that some of our novel RAMBAs may be useful agents for the treatment of prostate cancer

DNA damage in obesity: Initiator, promoter and predictor of cancer

Epidemiological evidence linking obesity with increased risk of cancer is steadily growing, although the causative aspects underpinning this association are only partially understood. Obesity leads to a physiological imbalance in the regulation of adipose tissue and its normal functioning, resulting in hyperglycaemia, dyslipidaemia and inflammation. These states promote the generation of oxidative stress, which is exacerbated in obesity by a decline in anti-oxidant defence systems. Oxidative stress can have a marked impact on DNA, producing mutagenic lesions that could prove carcinogenic. Here we review the current evidence for genomic instability, sustained DNA damage and accelerated genome ageing in obesity. We explore the notion of genotoxicity, ensuing from systemic oxidative stress, as a key oncogenic factor in obesity. Finally, we advocate for early, pre-malignant assessment of genome integrity and stability to inform surveillance strategies and interventions

Prognostic factors in prostate cancer

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking

Nutrition and cancer: A review of the evidence for an anti-cancer diet

It has been estimated that 30–40 percent of all cancers can be prevented by lifestyle and dietary measures alone. Obesity, nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes), low fiber intake, consumption of red meat, and imbalance of omega 3 and omega 6 fats all contribute to excess cancer risk. Intake of flax seed, especially its lignan fraction, and abundant portions of fruits and vegetables will lower cancer risk. Allium and cruciferous vegetables are especially beneficial, with broccoli sprouts being the densest source of sulforophane. Protective elements in a cancer prevention diet include selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids (α-carotene, β-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited benefits orally, but could be very beneficial intravenously. Supplementary use of oral digestive enzymes and probiotics also has merit as anticancer dietary measures. When a diet is compiled according to the guidelines here it is likely that there would be at least a 60–70 percent decrease in breast, colorectal, and prostate cancers, and even a 40–50 percent decrease in lung cancer, along with similar reductions in cancers at other sites. Such a diet would be conducive to preventing cancer and would favor recovery from cancer as well