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The role of antioxidants in reducing cancer initiation and progression has been highlighted in recent years. Not only antioxidants limit cancer cell growth but also, in some situations, they promote the effectiveness of conventional treatments. Melatonin, an endogenously synthesized antioxidant, reduces cell growth of several tumor types both in vivo and in vitro. Additionally, the indole limits the collateral damage induced by many chemotherapeutic agents. By using a cellular model of human prostate cancer, we studied the ability of melatonin to enhance apoptosis induced by tumor necrosis factor or gamma radiation. It has been reported that melatonin reduces prostate cancer cell growth and, more recently, it promotes cell differentiation. In this work, we also show that melatonin elevates p21 protein levels and increases antioxidant capacity of prostate cancer cells. In addition, melatonin significantly enhances hrTNFα induced cell death by decreasing NFκB activation. Bcl-2 and survivin down-regulation appears to be associated to apoptosis stimulation under NFκB inhibition. On the contrary, melatonin does not promote irradiation-induced cell death due to an increment in intracellular glutathione content. In conclusion, prevention of NFκB activation by melatonin enhances the effectiveness of cytokine treatment in prostate cancer cells but it is not sufficient to enhance cell death triggered by other therapies which generate free radicals. A crucial role of glutathione in survival mechanisms of prostate cancer cells should be carefully considered. [ABSTRACT FROM AUTHOR]

Genetic epidemiologists routinely assess disease susceptibility in relation to haplotypes, that is, combinations of alleles on a single chromosome. We study statistical methods for inferring haplotype-related disease risk using single nucleotide polymorphism (SNP) genotype data from matched case–control studies, where controls are individually matched to cases on some selected factors. Assuming a logistic regression model for haplotype-disease association, we propose two conditional likelihood approaches that address the issue that haplotypes cannot be inferred with certainty from SNP genotype data (phase ambiguity). One approach is based on the likelihood of disease status conditioned on the total number of cases, genotypes, and other covariates within each matching stratum, and the other is based on the joint likelihood of disease status and genotypes conditioned only on the total number of cases and other covariates. The joint-likelihood approach is generally more efficient, particularly for assessing haplotype-environment interactions. Simulation studies demonstrated that the first approach was more robust to model assumptions on the diplotype distribution conditioned on environmental risk variables and matching factors in the control population. We applied the two methods to analyze a matched case–control study of prostate cancer. [ABSTRACT FROM AUTHOR]

This article presents the results on a study to see if there is an association between hemodilution and a high serum prostate-specific antigen concentration (PSA) in obese men with prostate cancer. Obesity creates many problems, one of which is testing for cancer as their increased body mass index (BMI) can make detection more difficult. In the U.S. most prostate cancer patients are diagnosed after a needle biopsy which follows the discovery of a high PSA concentration. Any factor that decreases the PSA concentration level may confuse the tests and the study found that obese men do have more blood volume and may therefore have hemodilution of the PSA.

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 × 10−13; heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13–1.41; homozygote OR: 1.58, 95% c.i.: 1.40–1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 × 10−11; rs6983267 P = 6.62 × 10−10). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%). [ABSTRACT FROM AUTHOR]

Background Epidemiologic evidence indicates that aspirin use is associated with reduced risks of colon cancer and possibly several other cancers, including prostate and breast cancers. Recent results from the Women's Health Study randomized trial indicate that long-term use of low-dose aspirin (100 mg every other day) does not substantially reduce cancer risk. However, the potential effect of long-term daily use of higher doses of aspirin on cancer incidence remains uncertain. Methods We examined associations between long-term daily use of adult-strength aspirin (≥325 mg/day) and both overall cancer incidence and incidence of 10 types of cancer among 69810 men and 76303 women participating in the Cancer Prevention Study II Nutrition Cohort, a relatively elderly population. Aspirin use was reported at enrollment in 1992-1993 and updated in 1997, 1999, and 2001. Multivariable Cox proportional hazards regression was used to calculate rate ratios (RRs). Results During follow-up through June 2003, 10931 men and 7196 women were diagnosed with cancer. Long-term (≥5 years) daily use of adult-strength aspirin, compared with no use, was associated with lower over- all cancer incidence in men (multivariable-adjusted RR = 0.84, 95% confidence interval [CI] = 0.76 to 0.93) and non-statistically significantly lower overall cancer incidence in women (multivariable-adjusted RR = 0.86, 95% CI = 0.73 to 1.03). Overall cancer incidence per 100000 person-years (standardized to the age distributions of men and women in the study) with long-term daily aspirin use and no aspirin use was 1858 and 2163, respectively, among men and 1083 and 1169, respectively, among women. Long-term daily aspirin use was associated with lower incidence of colorectal cancer (RR = 0.68, 95% CI = 0.52 to 0.90 among men and women combined) and prostate cancer (RR = 0.81, 95% CI = 0.70 to 0.94) and a non-statistically significant lower risk of female breast cancer (RR = 0.83, 95% CI = 0.63 to 1.10). Conclusions Long-term daily use of adult-strength aspirin may be associated with modestly reduced overall cancer incidence in populations among whom colorectal, prostate, and breast cancers are common. [ABSTRACT FROM AUTHOR]

Folate has important roles in DNA synthesis, repair, and methylation and is inversely associated with the risk of some cancers. The authors examined this association among 65,836 men in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. During 9 years of follow-up, 5,158 men were diagnosed with prostate cancer. Folate intakes were estimated from the questionnaire administered at enrollment in 1992–1993, and Cox proportional hazards models were used to calculate hazard rate ratios adjusted for potential confounders. Neither dietary nor total folate intake was associated with prostate cancer overall. However, higher folate levels were associated with a nonsignificant decreased risk of advanced prostate cancer (multivariate rate ratio = 0.78, 95% confidence interval: 0.53, 1.15 for the highest vs. lowest quintiles of dietary folate and rate ratio = 0.79, 95% confidence interval: 0.54, 1.17 for the highest vs. lowest quintile of total folate). The association was similar for quintiles 2–5, suggesting that only a small increase in folate intake was needed to alter the risk of advanced prostate cancer. Because the statistical power of the analysis with advanced prostate cancer was limited by the low number of cases, further study is needed to establish this association. [ABSTRACT FROM AUTHOR]

Background: Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has consistently been associated with a reduced risk of colon cancer. Recent epidemiologic studies have suggested that the use of NSAIDs, particularly aspirin, may also be associated with a reduced risk of prostate cancer, but the evidence remains limited. Methods: We examined the association between NSAID use and prostate cancer incidence among 70144 men in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. Information on NSAID use was obtained from a questionnaire completed at study enrollment in 1992-1993 and was updated using follow-up questionnaires in 1997 and 1999. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) for prostate cancer incidence associated with NSAID use, adjusting for age and potential prostate cancer risk factors. Results: During follow-up from 1992-1993 through August 31, 2001, 4853 cases of incident prostate cancer were identified. Neither current aspirin use nor current use of NSAIDs (aspirin and other NSAIDs combined) was associated with prostate cancer risk, even at the highest usage level (60 or more pills per month). However, long-duration regular use (30 or more pills per month for 5 or more years) of NSAIDs was associated with reduced risk of prostate cancer (RR = 0.82, 95% CI = 0.71 to 0.94). Long-duration regular use of aspirin was also associated with reduced risk of prostate cancer (RR = 0.85, 95% CI = 0.73 to 0.99). The absolute rate of prostate cancer (standardized to the age distribution of study participants using 5-year age categories) was 1013 per 100 000 person-years among men who had never reported NSAID use, and 847 per 100 000 person-years among long duration regular NSAID users. Conclusions: These results support the hypothesis that long duration regular NSAID use is associated with modestly reduced risk of prostate cancer. [ABSTRACT FROM AUTHOR]

One previous study has suggested that diabetes may decrease risk of prostate cancer but only several years after diagnosis of diabetes. The authors examined the role of timing of diabetes diagnosis in relation to risk of prostate cancer among men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a mailed questionnaire including information on diabetes at enrollment in 1992 and at follow-up questionnaires in 1997 and 1999. Historical information on diabetes was also available from a previous study in 1982. The authors documented 5,318 cases of incident prostate cancer through August 31, 2001, among 72,670 men. Results from Cox proportional hazards models showed that diabetes was associated with a lower incidence of prostate cancer (rate ratio (RR) = 0.67, 95% confidence interval (CI): 0.60, 0.75). This association differed significantly by time since diagnosis of diabetes (p < 0.0002); risk of prostate cancer was slightly increased during the first 3 years after diagnosis of diabetes (RR = 1.23, 95% CI: 0.92, 1.65) but was reduced among men diagnosed 4 or more years before (RR = 0.63, 95% CI: 0.56, 0.71). Study results are consistent with the hypothesis that diabetes is associated with reduced risk of prostate cancer but only several years after diagnosis of diabetes. [ABSTRACT FROM AUTHOR]