Selenium and Cadmium Levels and Ratios in Prostates,Livers, and Kidneys of Nonsmokers and Smokers

Cadmium (Cd) from cigarette smoke, environmental, and nutritional sources accumulates in the human prostate where it interacts with selenium (Se) in a manner suggesting the formation of a 1:1 Cd–Se–protein complex. At low Cd exposures and adequate Se status, this interaction may be beneficial as it results in the detoxification of Cd. At higher exposures, Cd may weaken or abolish the anticarcinogenic effects of Se and increase prostate cancer risk. In some older men and especially in smokers, Cd levels in prostates reach levels in stoichiometric excess over Se, which may be the reason why heavy smokers are at higher risk of developing lethal forms of prostate cancer. In the liver and the kidneys, Cd accumulates as well, but in these organs, Cd is efficiently sequestered through metallothionein formation. In the prostate, this mode of detoxification is not available or less efficient, causing Cd to interact with Se and to increase prostate cancer risk.     

Oxidative DNA Damage in the Prostate May Predispose Men to a Higher Risk of Prostate Cancer

DNA damage has been associated with prostate cancer risk. Men who were referred for initial prostate biopsy for elevated prostate-specific antigen or abnormal digital rectal examination are often found with no cancer but have a higher risk of developing prostate cancer than the general population of men in their lifetime. In this study, we investigated whether DNA damage is one of the factors that predispose these men referred for prostate biopsies to a higher risk of prostate cancer. We found significantly elevated levels of 8-oxo-2-deoxyguanosine immunoreactivity in the prostates of the referred men (n = 50) in comparison to the control prostates of men (n = 32) with no indication for referral for prostate biopsy. Twelve of these control men were healthy middle-aged men and 20 of them were older men whose conditions were diagnosed with bladder cancer but with normal serum prostate-specific antigen and digital rectal examination and no evidence of prostate disease. In all the 8-oxo-2-deoxyguanosine-positive prostates, we detected phosphorylation of the ataxia telangiectasia mutated kinase and expression of the immune-stimulatory molecule MIC in the prostate epithelium. These data suggest that: 1) oxidative DNA damage has occurred in the “referred” but pathologically normal prostates, indicating that these prostates may be subjected to genomic instability and eventually neoplastic transformation; 2) in response to DNA damage, two surveillance pathways, represented by ataxia telangiectasia mutated phosphorylation and induction of the NKG2D ligand MIC, were activated to prevent tumorigenesis.     

Smoking does not influence cadmium concentrations in blood and urine in relatively high levels of environmental cadmium areas in Japan

We examined how the influence of smoking on blood and urinary cadmium (Cd) concentrations was modified by the level of environmental Cd. We measured blood and urinary Cd concentrations of 1134 men over 50 yr of age in three areas in Japan that were exposed to different levels of environmental Cd. Analysis of variance was used to compare Cd concentrations in blood and urine of smokers with those of nonsmokers living in the three areas. Correlation coefficients between the number of cigarets smoked per day or smoking indices (the number of cigarets smoked per day multiplied by the number of years smoked) and blood and urinary Cd concentrations were calculated. No significant difference in Cd concentrations between smokers and nonsmokers was observed in areas where the average Cd concentration in blood was over approx 2.4 ng/g, 2.0 μg/L in urine, and 2.3 μg/g creatinine in urine, respectively. Therefore, it was suggested that an influence of smoking on blood and urinary Cd concentrations was not observed in areas exposed to relatively high levels of environmental Cd.     

Circulating Thyroxine,Thyroid-Stimulating Hormone,and Hypothyroid Status and the Risk of Prostate Cancer

Background

Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

Methods

Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2∶1 to cases on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of thyroid status.

Results

Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1–4: OR = 0.70, 95% CI: 0.51–0.97, p = 0.03). When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28–0.81, p = 0.006). We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9).

Conclusions

In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.     

Simultaneous Determination of Cd, Pb, Cu, Zn, and Se in Human Blood of Jordanian Smokers by ICP-OES

A total of 73 blood samples (56 from smokers and 17 from nonsmokers) were collected to determine the concentrations of selected heavy metal in the whole blood of smokers and nonsmokers living in and around the city of Amman, Jordan. Analysis of heavy metals in the whole blood samples of various groups took in consideration the number of cigarettes smoked per day. The analysis of blood samples was carried out using inductively coupled plasma optical emission spectrometry. This study aimed to evaluate the blood metal levels in smokers and nonsmokers and to assess the influence of smoking cigarettes on blood metal levels. The results were compared with those from a control group. The results indicated that the average concentrations of cadmium (Cd), lead (Pb), copper (Cu), zinc (Zn), and selenium (Se) were 0.0313, 0.344, 2.328, 3.214, and 0.332 mg/L, respectively. Statistical analysis of results indicated that these average concentrations were significantly higher compared with the average concentrations in nonsmokers (P < 0.05). Moreover, the correlations between blood metal and other blood metal levels in smokers, the correlations between blood metal and other blood metal levels in nonsmokers, and the correlations between blood metal concentration in smokers and its concentration in nonsmokers were calculated. The standard reference material (blood serum National Institute of Standards and Technology 1598) and the quality control were used to validate the reliability of the method used for the estimation of heavy metals in blood samples. Results revealed that there was an agreement between the certified values and the measured values.     

Consumption of Fish Products across the Lifespan and Prostate Cancer Risk

Objective

To examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer.

Design

The study was nested among 2268 men aged 67–96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption.

Results

Among the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption.

Conclusions

Salted or smoked fish may increase risk of advanced prostate cancer, whereas fish oil consumption may be protective against progression of prostate cancer in elderly men. In a setting with very high fish consumption, no association was found between overall fish consumption in early or midlife and prostate cancer risk.     

High Levels of Cadmium and Lead in Seminal Fluid and Blood of Smoking Men are Associated with High Oxidative Stress and Damage in Infertile Subjects

We measured the levels of malondialdehyde (MDA), protein carbonyls, glutathione S-transferase (GST) and reducte glutathione (GSH) in seminal plasma and spermatozoa from 95 subjects including 50 infertile patients to evaluate the association between oxidative stress and damage and the components of the anti-oxidant defenses in seminal plasma and spermatozoa of infertile subjects and concentrations of cadmium (Cd) and lead (Pb) in the blood and seminal plasma because of tobacco smoke exposure. The reactive oxygen species (ROS) in spermatozoa were also evaluated by luminol (5-amino-2,3-dihydro-1,4-phthalazinedione)-enhanced chemiluminescence assay. The sperm count, motility, and morphology in the smokers infertile group were found to be lower than those in the fertile male group and nonsmokers infertile group (p < 0.001). Concentrations of Cd, Pb, MDA, protein carbonyls, and ROS levels in the smokers infertile group were significantly higher than those in the fertile male and nonsmokers infertile male groups (p < 0.001). However, GSH levels and GST activities were decreased in the smokers infertile male group than those in the fertile male and nonsmokers infertile male groups (p < 0.001). The results indicate that smoking could affect semen quality and oxidative lipid and protein damage in human spermatozoa. From Pearson correlation analysis, positive correlations were demonstrated between the seminal plasma Cd and seminal plasma protein carbonyls and between seminal plasma Pb and spermatozoa ROS levels in smokers of the subfertile group, while there was a significant positive correlation between blood Cd and ROS levels in smokers of the fertile group. There was also a significant negative correlation of the Cd level of the blood and GSH levels of the sperm and seminal plasma. These findings suggest that cigarette smoking enhances the levels of Cd and Pb in seminal plasma and blood and the extent of oxidative damage associated with a decrease in components of the anti-oxidant defenses in the sperm of infertile males.     

Evidence for autosomal dominant inheritance of prostate cancer.

A family-history cancer survey was conducted on 5,486 men who underwent a radical prostatectomy, for clinically localized prostate cancer, in the Department of Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey. Complex segregation analysis was performed to assess the genetic basis of age at diagnosis and the familial clustering of prostate cancer. For the total group, no single-gene model of inheritance clearly explained familial clustering of disease, which could be partly explained by lack of Hardy-Weinberg equilibrium, with an excess of homozygotes. After accounting for deviations from Hardy-Weinberg equilibrium, the best-fitting model that explained the familial aggregation and age at diagnosis was a rare autosomal dominant susceptibility gene, and this model fitted best when probands were diagnosed at <60 years of age. The model predicts that the frequency of the susceptibility gene in the population is .006 and that the risk of prostate cancer by age 85 years is 89% among carriers of the gene and 3% among noncarriers. A strength of our study is its large size, such that genetic models could be fitted within strata defined by the age of the proband. Although the autosomal dominant model was consistently the best model, the parameter estimates differed somewhat (P=.03) across the different age groups, suggesting genetic heterogeneity. Additional evidence that the hereditary basis of prostate cancer is likely to be genetically complex was provided by the following: (1) there was a significantly elevated age-adjusted risk of prostate cancer among brothers of probands, compared with their fathers (relative risk 1.5 [95% confidence interval 1.4-1.7]); (2) the autosomal dominant model predicted an excess of homozygotes, over that predicted by Hardy-Weinberg equilibrium; and (3) the model-predicted risk of prostate cancer among relatives was inadequate when probands were diagnosed at age >=70 years.     

Serum α-tocopherol and γ-tocopherol concentrations and prostate cancer risk in the PLCO Screening Trial: a nested case-control study

Background

Vitamin E compounds exhibit prostate cancer preventive properties experimentally, but serologic investigations of tocopherols, and randomized controlled trials of supplementation in particular, have been inconsistent. Many studies suggest protective effects among smokers and for aggressive prostate cancer, however.

Methods

We conducted a nested case-control study of serum α-tocopherol and γ-tocopherol and prostate cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, with 680 prostate cancer cases and 824 frequency-matched controls. Multivariate-adjusted, conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tocopherol quintiles.

Results

Serum α-tocopherol and γ-tocopherol were inversely correlated (r = −0.24, p<0.0001). Higher serum α-tocopherol was associated with significantly lower prostate cancer risk (OR for the highest vs. lowest quintile = 0.63, 95% CI 0.44–0.92, p-trend 0.05). By contrast, risk was non-significantly elevated among men with higher γ-tocopherol concentrations (OR for the highest vs. lowest quintile = 1.35, 95% CI 0.92–1.97, p-trend 0.41). The inverse association between prostate cancer and α-tocopherol was restricted to current and recently former smokers, but was only slightly stronger for aggressive disease. By contrast, the increased risk for higher γ-tocopherol was more pronounced for less aggressive cancers.

Conclusions

Our findings indicate higher α-tocopherol status is associated with decreased risk of developing prostate cancer, particularly among smokers. Although two recent controlled trials did not substantiate an earlier finding of lower prostate cancer incidence and mortality in response to supplementation with a relatively low dose of α-tocopherol, higher α-tocopherol status may be beneficial with respect to prostate cancer risk among smokers. Determining what stage of prostate cancer development is impacted by vitamin E, the underlying mechanisms, and how smoking modifies the association, is needed for a more complete understanding of the vitamin E-prostate cancer relation.     

Estimation of Toxic Metals in Scalp Hair Samples of Chronic Kidney Patients

The determination of toxic metals (TMs) in the biological samples of human beings is an important clinical screening procedure. The aim of this work is to determine total content of TMs, aluminum (Al), cadmium (Cd), nickel (Ni), and lead (Pb) in scalp hair samples of chronic kidney male patients (CKPs) on maintenance hemodialysis, during the period of 2005–2007. The study included 115 CKPs (all smokers) and 150 controls or referents [82 (nonsmokers) and 68 (smokers)]. Both controls and patients (males) were of the same age group (ranged 25–55 years), socioeconomic status, localities, and dietary habits. The scalp hair samples were analyzed by electrothermal atomic absorption spectrometer, prior to microwave-induced acid digestion. The accuracy of the total Al, Cd, Ni, and Pb measurements was tested by simultaneously analyzing certified reference material (human hair NCS ZC81002). No significant differences were observed between the analytical results and the certified values (paired t test at p > 0.05). The levels of TMs in scalp hair samples of patients were found to be higher as compared to control nonsmoker and smokers. Moreover, the study shows that levels of Al, Cd, Ni, and Pb in scalp hair samples may be useful to evaluate the impact of cigarette smoking in kidney failure patients.     

Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8

Objective To assess the risk of lung cancer in smokers of medium tar filter cigarettes compared with smokers of low tar and very low tar filter cigarettes.Design Analysis of the association between the tar rating of the brand of cigarette smoked in 1982 and mortality from lung cancer over the next six years. Multivariate proportional hazards analyses used to assess hazard ratios, with adjustment for age at enrolment, race, educational level, marital status, blue collar employment, occupational exposure to asbestos, intake of vegetables, citrus fruits, and vitamins, and, in analyses of current and former smokers, for age when they started to smoke and number of cigarettes smoked per day.Setting Cancer prevention study II (CPS-II).Participants 364 239 men and 576 535 women, aged ≥ 30 years, who had either never smoked, were former smokers, or were currently smoking a specific brand of cigarette when they were enrolled in the cancer prevention study.Main outcome measure Death from primary cancer of the lung among participants who had never smoked, former smokers, smokers of very low tar (≤ 7 mg tar/cigarette) filter, low tar (8-14 mg) filter, high tar (≥ 22 mg) non-filter brands and medium tar conventional filter brands (15-21 mg).Results Irrespective of the tar level of their current brand, all current smokers had a far greater risk of lung cancer than people who had stopped smoking or had never smoked. Compared with smokers of medium tar (15-21 mg) filter cigarettes, risk was higher among men and women who smoked high tar (≥ 22 mg) non-filter brands (hazard ratio 1.44, 95% confidence interval 1.20 to 1.73, and 1.64, 1.26 to 2.15, respectively). There was no difference in risk among men who smoked brands rated as very low tar (1.17, 0.95 to 1.45) or low tar (1.02, 0.90 to 1.16) compared with those who smoked medium tar brands. The same was seen for women (0.98, 0.80 to 1.21, and 0.95, 0.82 to 1.11, respectively).Conclusion The increase in lung cancer risk is similar in people who smoke medium tar cigarettes (15-21 mg), low tar cigarettes (8-14 mg), or very low tar cigarettes (≤ 7 mg). Men and women who smoke non-filtered cigarettes with tar ratings ≥ 22 mg have an even higher risk of lung cancer.     

Increased levels of NAD(P)H: quinone oxidoreductase 1 (NQO1) in pancreatic tissues from smokers and pancreatic adenocarcinomas: A potential biomarker of early damage in the pancreas

NAD(P)H:quinone oxidoreductase 1 (NQO1) is elevated in several human tumors. This study was conducted to determine whether increased levels of NQO1 expression also occur in human pancreatic tumor tissue, and to compare expression levels in nontumorous tissue from smokers with those in nonsmokers. The expression of NQO1 was examined in pancreatic tissue samples from 82 human donors. These samples included normal (n = 20), smokers (n = 25), pancreatitis (n = 7), and adenocarcinomas of the pancreas (n = 30). Genotyping for the C609T polymorphism in NQO1 by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis was also performed. Polymorphic variants were confirmed by automatic sequencing. Higher levels of NQO1 expression were demonstrated in pancreatic adenocarcinomas (0.831 ± 0.021) compared to those in nontumorous tissues from nonsmokers (0.139 ± 0.024). These high levels were also found in smokers (0.729 ± 0.167) and in pancreatitis tissues (0.923 ± 0.184). NQO1 activity was also higher in smokers (2.43 ± 0.61 nmol/min per mg protein) compared to nonsmokers (0.44 ± 0.05 nmol/min per mg protein; p < 0.05). No differences were found in genotype distribution and frequencies of the variant alleles between normal and cancer tissues in this relatively small sample pool. Seventy-five percent of the normal pancreatic tissues showed 609(C/C) and 25% 609(C/T). In pancreatic adenocarcinomas the frequency distribution was 65% C/C, 30% C/T and 5% T/T. The increased expression in noncancer pancreatic tissue from smokers and the fact that smoking is a moderate risk factor for pancreatic cancer suggest that NQO1 expression may be a good candidate as a biomarker for pancreatic cancer, especially in risk groups such as smokers.     

Prostate Tissue Metal Levels and Prostate Cancer Recurrence in Smokers

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N?=?25) had significantly higher Cd (median ppb, p?=?0.03) and lower Zn (p?=?0.002) in non-neoplastic tissue than never-smokers (N?=?21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p?=?0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p?=?0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p?=?0.039 and adjacent non-neoplastic, p?=?0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.     

Fingerprinting the diseased prostate: associations between BPH and prostate cancer

Two of the most common diseases which occur in ageing men relate to their prostate. BPH and prostate cancer are prevalent diseases which have an impact on most men as they age. The advent of gene expression analysis has provided an opportunity to examine these diseases in a novel fashion. These analyses, to date, have revealed associations between these two diseases which have not been previously identified. These commonalities include global genetic changes which occur throughout the prostates in individuals with these diseases. Understanding the fingerprints of these diseases is providing novel markers and treatment strategies for both BPH and prostate cancer.     

Effects of Cadmium Chloride and Sodium Selenite Alone or in Combination on the Liver of Male Sprague–Dawley Rats Assessed by Different Assays

This study assessed the impact of either cadmium chloride (Cd) or sodium selenite (Se) alone or in combination on male Sprague–Dawley rats. For this purpose, body and liver weights, comet and TUNEL assays, histological analysis and levels of lipid peroxidation and antioxidants in liver were determined in four groups of male Sprague–Dawley rats. The rats were given subcutaneous doses of 1 mg/kg body weight (BW) of either normal saline (control = Ct) or Cd or Se or Cd plus Se (Cd + Se) on alternate days for 4 weeks. The Cd group showed increased DNA damage, apoptosis and hepatic levels of lipid peroxidation and altered histology. Conversely, the antioxidant levels in this group were decreased as compared with the control group. The Se group also showed DNA damage, apoptosis and altered histology and reduced catalase activity, but it was less severe than the Cd group. In the Cd + Se group, ameliorating effects of Se on Cd-induced changes were observed. While the Se was able to curtail the toxic effect of Cd, the Cd or Se alone were genotoxic and cytotoxic for rats receiving a high pharmacological but non-fatal dose of 1 mg/kg BW.     

Risk of Second Primary Cancer among Prostate Cancer Patients in Korea: A Population-Based Cohort Study

As patients with prostate cancer have a long life expectancy, there is increasing interest in predicting the risk of development of a second primary cancer (SPC), and we therefore designed this study to estimate the overall risk of developing SPCs among Korean prostate cancer patients. We used a population-based cohort from the Korean Central Cancer Registry composed of 55,378 men diagnosed with a first primary prostate cancer between 1993 and 2011. Standardized incidence ratios (SIRs) of SPCs were analyzed by age at diagnosis, latency period, period of diagnosis, and type of initial treatment. Survival analysis was stratified by development of SPC. Men with primary prostate cancer had an overall lower risk of developing an SPC [SIR = 0.75; 95% CI, 0.72−0.78], which was significant for SPCs of the esophagus, stomach, rectum, liver, gallbladder, bile duct, pancreas, larynx, lung, and bronchus. In contrast, there were significant increases in the risk of bladder and thyroid cancers, which tended to decrease after longer follow-up. Patients who received initial radiation therapy had an increased risk of subsequent rectal cancer, although this was still lower than that of the general male population. Other urinary tract cancers including those of the kidney, renal pelvis, and ureter tended to be associated with a higher risk of developing an SPC, but this difference did not reach statistical significance. The patients with prostate cancer and SPC had lower overall survival rates than those with one primary prostate cancer. Our findings suggest that men with prostate cancer have a 25% lower risk of developing an SPC in Korea, but a higher risk of developing subsequent bladder and thyroid cancers, which suggests the need for continued cancer surveillance among prostate cancer survivors.     

Genetic Susceptibility Loci,Pesticide Exposure and Prostate Cancer Risk

Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44–8.15) (P-interaction  = 0.003). Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41) (P-interaction  = 0.006). In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.     

Age-Related Changes of the Concentrations of Select Elements in the Prostates of Japanese

To elucidate compositional changes of the prostate with aging, the authors investigated age-related changes of elements in the prostates and the relationships among their elements using Japanese and Thai. After ordinary dissections by students at Nara Medical University and Chiang Mai University were finished, the prostates were resected from the subjects. Fifty-seven Japanese subjects ranged in age from 65 to 101 years (average age = 82.5 ± 7.8 years), whereas 13 Thai subjects ranged in age from 43 to 86 years (average age = 67.9 ± 11.9 years). After ashing with nitric acid and perchloric acid, element contents were determined by inductively coupled plasma–atomic emission spectrometry. It was found that although there were no significant correlations between age and seven element contents, such as Ca, P, S, Mg, Zn, Fe, and Na, in the prostates of Japanese, high contents of Ca (>5 mg/g) and P (>4 mg/g) were contained in one fourth of the prostates of Japanese over 70 years of age. In the prostates of Thai, a significant direct correlation was found between age and Ca content, but it was not found between age and the other element contents, such as P, S, Mg, Zn, Fe, and Na. Regarding the relationships among their elements, extremely significant direct correlations were found among the contents of Ca, P, Mg, Zn, and Na in the prostates of Japanese. In the prostates of Thai, significant direct correlations were found among the contents of Ca, Mg, and Zn, but no significant correlations were found between Ca and P contents and between P and Mg contents. Regarding the relationships among their elements, there were differences between the prostates of Japanese and Thai. To examine whether element contents changed in prostatic hypertrophy, the transverse width of the Japanese prostates was measured. No significant correlations were found between the transverse width and element contents, such as Ca, P, S, Mg, Zn, Fe, and Na, in the Japanese prostates. Therefore, it is unlikely that the increase of elements results in prostatic hypertrophy.     

ICAM gene cluster SNPs and prostate cancer risk in African Americans

Intercellular adhesion molecules (ICAMs) are known to be involved in various human cancers. An ICAM gene cluster lying within a 26 kb region on chromosome 19p13.2, and containing ICAM1, ICAM4, and ICAM5 has recently been identified as harboring a breast and prostate cancer susceptibility locus in two populations of European ancestry from Germany and Australia. The objective of this study was to confirm the ICAM association with prostate cancer in a sample of African American prostate cancer cases (N = 286) and controls (N = 391). Six single nucleotide polymorphisms (SNPs) within the three ICAM genes were genotyped. To control for potential population stratification an ancestry-adjusted association analysis was performed. We found that ICAM1 SNPs, −9A/C (rs5490) and K469E (rs5498) were associated with prostate cancer risk in men with a family history of prostate cancer (P = 0.008). Specifically, increased risk was observed for individuals who possessed the CC genotype of the −9 A/C variant (odds ratio = 2.5; 95% CI = 1.0–6.3) and at least one G allele of non-synonymous K469E variant (odds ratio = 1.8; 95% CI = 1.2–3.1). Strong linkage disequilibrium was observed across the ICAM region (P < 0.001). A common haplotype within the ICAM gene cluster, harboring the −9A/C variant was significantly associated with prostate cancer (P = 0.03), mainly due to men with family history (P = 0.01). Our results replicate previous findings of association of the ICAM gene cluster with prostate cancer and suggest that common genetic variation within ICAM1 and not ICAM5 may be an important risk factor for prostate cancer.     

Residential Exposure to Road and Railway Noise and Risk of Prostate Cancer: A Prospective Cohort Study

Background

Few modifiable risk factors for prostate cancer are known. Recently, disruption of the circadian system has been proposed to affect risk, as it entails an inhibited melatonin production, and melatonin has demonstrated beneficial effects on cancer inhibition. This suggests a potential role of traffic noise in prostate cancer.

Methods

Road traffic and railway noise was calculated for all present and historical addresses from 1987–2010 for a cohort of 24,473 middle-aged, Danish men. During follow-up, 1,457 prostate cancer cases were identified. We used Cox Proportional Hazards Models to calculate the association between noise exposure and incident prostate cancer. Incidence Rate Ratios (IRR) were calculated as crude and adjusted for smoking status, education, socioeconomic position, BMI, waist circumference, physical activity, calendar year, and traffic noise from other sources than the one investigated.

Results

There was no association between residential road traffic noise and risk of prostate cancer for any of the three exposure windows: 1, 5 or 10-year mean noise exposure before prostate cancer diagnosis. This result persisted when stratifying cases by aggressiveness. For railway noise, there was no association with overall prostate cancer. There was no statistically significant effect modification by age, education, smoking status, waist circumference or railway noise, on the association between road traffic noise and prostate cancer, although there seemed to be a suggestion of an association among never smokers (IRR: 1.16; 95% CI: 1.00–1.36).

Conclusion

The present study does not support an overall association between either railway or road traffic noise and overall prostate cancer.