Prevalent diabetes and risk of total,colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Background We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I² = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I² = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I² = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I² = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I² = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.Subject terms: Risk factors, Cancer epidemiology     

Evaluating Family History Links between Breast Cancer and Prostate Cancer Among PLCO Trial Participants

IntroductionThe objective of this study was to assess family history links between breast cancer and prostate cancer in a prospectively collected cohort from the Prostate, Lung, Colorectal, and Ovary (PLCO) trial.Patients and MethodsThis is a secondary analysis of the PLCO trial datasets. Eligible patients included female participants with complete information about prostate cancer family history and male participants with complete information about breast cancer family history. Multivariate Cox regression analysis was used to assess the impact of prostate cancer family history on breast cancer incidence and mortality. Likewise, multivariate Cox regression analysis was used to assess the impact of breast cancer family history on prostate cancer incidence and mortality.ResultsA total of 45,807 female participants were eligible and included in the current study, and a total of 43,009 male participants were eligible and included in the current analysis. Within a multivariate Cox regression analysis, prostate cancer family history in a first-degree relative (FDR) was associated with a higher probability of diagnosis of breast cancer (hazard ratio [HR], 1.128; 95% confidence interval [CI], 1.007-1.265; P = .038); whereas it was not associated with a higher risk of death from breast cancer (HR, 1.065; 95% CI, 0.668-1.698; P = .791). Similarly, within a multivariate Cox regression analysis, breast cancer family history in an FDR was associated with a higher probability of diagnosis of prostate cancer (HR, 1.092; 95% CI, 1.011-1.180; P = .026) but not death from prostate cancer (HR, 0.442; 95% CI, 0.137-1.432; P = .173).ConclusionsFemale participants with a family history of prostate cancer in an FDR were more likely to develop postmenopausal breast cancer. Likewise, male participants with a family history of breast cancer in an FDR are at a higher probability of prostate cancer development. Risk correlation for premenopausal breast cancer could not be assessed owing to the nature of the PLCO study.     

Childhood height increases the risk of prostate cancer mortality

BackgroundAdult body size is positively associated with aggressive and fatal prostate cancers. It is unknown whether these associations originate in early life. Therefore, we investigated if childhood height, body mass index (BMI; kg/m²) and growth are associated with prostate cancer-specific mortality and survival.MethodsSubjects were 125,208 men from the Copenhagen School Health Records Register, born 1930–1969 with height and weight measurements at ages 7–13 years. Linkage to the Danish Cancer Registry and the Register of Causes of Death enabled identification of incident and fatal prostate cancers. Cox proportional hazards regressions were performed.Results630 men had prostate cancer recorded as the underlying cause of death. Childhood height at age 13 years was positively associated with prostate cancer-specific mortality (hazard ratio [HR]_{per z-score} = 1.2, 95% confidence interval [CI]: 1.1–1.3). Associations were significant at all other childhood ages. Growth analyses showed that height at age 13 years had a stronger association with prostate cancer-specific mortality than height at age 7, suggesting the association at age 7 is largely mediated through later childhood height. The tallest boys at age 13 years had a significantly worse survival, but only when restricted to a diagnosis at <60 years of age (HR_{z-score of 1} = 1.7, 95% CI: 1.3–2.4). These associations were significant at all other childhood ages. Childhood BMI was not associated with prostate cancer mortality or survival.ConclusionChildhood height was positively associated with the hard end-point of prostate cancer-specific mortality, which strengthens prior epidemiologic observations of a positive association with prostate cancer incidence.     

Identification of Differential Patterns of Oxidative Biomarkers in Prostate Cancer Progression

IntroductionOxidative stress has been found to be associated with the progression of prostate cancer (PCa); however, human studies which identify differential roles of each oxidation pathway in PCa progression are lacking. We aimed to identify which oxidative stress markers, specifically lipid and global oxidation and glycation, are associated with PCa progression.Patients and MethodsWe recruited 3 groups of patients from a urologic clinic at the University of Cincinnati Medical Center: men with PCa who had undergone prostatectomy, men with PCa under watchful waiting, and men with benign prostatic hyperplasia (BPH). We used the most commonly used lipid oxidation marker, F2-isoprostanes; global oxidation markers, fluorescent oxidation products (FlOPs); and the commonly used marker for advanced glycation end products, carboxymethyllysine. These biomarkers were measured in plasma samples at baseline entry. Plasma prostate-specific antigen (PSA) was measured at enrollment and follow-up visits.ResultsCompared with men with BPH, men with PCa who had undergone prostatectomy had 26% (P = .01) higher levels of F2-isoprostanes and 20% (P = .08) higher levels of carboxymethyllysine. All the oxidation markers were similar when comparing men under watchful waiting with men with BPH. When examining the associations between baseline oxidation markers and follow-up PSAs, we found that different oxidation markers had differential patterns associated with PSA elevation. F2-isoprostanes were positively associated with PSA elevation among men with PCa; FlOP_320 was positively associated with PSA elevation among both men with PCa and men with BPH, whereas among men with PCa under watchful waiting, FlOP_360 and FlOP_400 had opposite trends of associations with PSA elevation.ConclusionsOur study suggested that high levels of lipid oxidation were associated with PCa progression, whereas different global oxidation markers had different patterns associated with PCa progression. Large-scale clinical studies are needed to confirm our associations. Our study provides a comprehensive view of the relationship between biomarkers and PCa progression.     

Plasma phospholipid fatty acids,dietary fatty acids and prostate cancer risk

Animal and experimental studies have demonstrated that long‐chain n‐3 fatty acids inhibit the development of prostate cancer, whereas n‐6 fatty acids might promote it. We performed a case–cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 1,717 men and 464 prostate cancer cases to investigate associations between fatty acids assessed in plasma phospholipids (PPLs) or diet (estimated using a 121‐item food frequency questionnaire) and prostate cancer risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Prostate cancer risk was positively associated with %PPL saturated fatty acids (SFAs); HR [95% CI] = 1.51 [1.06, 2.16] (Q5 vs. Q1, fifth vs. first quintile); p‐trend = 0.003. HRs (Q5 to Q2 vs. Q1) were significantly elevated for %PPL palmitic acid. %PPL oleic acid was inversely associated with risk, HR = 0.62 [0.43, 0.91] (Q5 vs. Q1); p‐trend = 0.04. No statistically significant linear trends were observed for dietary intakes. The HRs were elevated for moderate intakes of linoleic acid (Q2 and Q3 vs. Q1, 1.58 [1.10, 2.28] and 1.70 [1.18, 2.46], respectively), but the increase was not significant for higher intakes (Q4 and Q5). No association varied significantly by tumour aggressiveness (all p‐homogeneity > 0.1). Prostate cancer risk was positively associated with %PPL SFA, largely attributable to palmitic acid and inversely associated with %PPL monounsaturated fatty acids, largely attributable to oleic acid. Higher risks were also observed for dietary n‐6 polyunsaturated fats, primarily linoleic acid.     

Dietary fat intake and risk of prostate cancer: A prospective study of 25,708 Norwegian men

The relationship between incidence of prostate cancer and intake of dietary fat and foods rich in fat was studied in 25,708 men aged 16–56 years attending a Norwegian health screening in 1977–1983. Linkage to the Cancer Registry of Norway and the Central Bureau of Statistics of Norway ensured a complete follow-up until December 31, 1992. Diet was recorded on a semi-quantitative food-frequency questionnaire at the time of screening, and 72 cases of prostate cancer were identified during follow-up. At the end of follow-up, mean age of the total study sample was 56 years (range 19–68), while mean age at diagnosis of prostate cancer was 60 years (range 47–67). No association was found between energy-adjusted intake of total fat, saturated fat, mono-unsaturated fat or poly-unsaturated fat and the incidence of prostate cancer. Significant positive associations were found for body mass index (BMI) and consumption of hamburgers/meatballs, while no association was found with consumption of frankfurters/sausages and a significant negative association with the weekly number of main meals with meat. A significantly increased risk of prostate cancer was associated with skim milk as compared to whole milk. Milk preference (skim vs. whole) was associated significantly positively with BMI. Our study of a relatively young cohort does not confirm previous case-control and cohort studies suggesting that dietary fat, especially from animal sources, is associated positively with risk of prostate cancer. Int. J. Cancer 73:634–638, 1997. © 1997 Wiley-Liss, Inc.     

Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study

Inflammation is a well‐documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C‐reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06–1.56, 1.32; 1.05–1.65 and 1.51; 1.26–1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10–1.74, 1.50; 1.17–1.93 and 1.25; 1.00–1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02–1.86) and overall death (HR_{unit increase in log}: 1.60; 95% CI: 1.11–2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56–0.89 and 0.72; 0.5 9–0.90). WBC was associated with increased odds of T3–T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.     

Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study

BackgroundOld age at prostate cancer diagnosis has been associated with poor prognosis in several studies. We aimed to investigate the association between age at diagnosis and prognosis, and if it is independent of tumor characteristics, primary treatment, year of diagnosis, mode of detection and comorbidity.Patients and methodsWe conducted a nation-wide cohort study including 121 392 Swedish men aged 55–95 years in Prostate Cancer data Base Sweden 3.0 diagnosed with prostate cancer in 1998–2012 and followed for prostate cancer death through 2014. Data were available on age, stage, grade, prostate-specific antigen (PSA)-level, mode of detection, comorbidity, educational level and primary treatment. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsWith increasing age at diagnosis, men had more comorbidity, fewer PSA-detected cancers, more advanced cancers and were less often treated with curative intent. Among men with high-risk or regionally metastatic disease, the proportion of men with unknown M stage was higher among old men versus young men. During a follow-up of 751 000 person-years, 23 649 men died of prostate cancer. In multivariable Cox-regression analyses stratified by treatment, old age at diagnosis was associated with poorer prognosis among men treated with deferred treatment (HRage 85+ versus 60–64: 7.19; 95% CI: 5.61–9.20), androgen deprivation therapy (HRage 85+ versus 60–64: 1.72; 95% CI: 1.61–1.84) or radical prostatectomy (HRage 75+ versus 60–64: 2.20; 95% CI: 1.01–4.77), but not radiotherapy (HRage 75+ versus 60–64: 1.08; 95% CI: 0.76–1.53).ConclusionOur findings argue against a strong inherent effect of age on risk of prostate cancer death, but indicate that in current clinical practice, old men with prostate cancer receive insufficient diagnostic workup and subsequent curative treatment.     

Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study

Purpose

African American men have the highest incidence of prostate cancer among ethnic groups, and racial disparity is highest in younger men. Prostate cancer prevalence is rising in HIV-infected men due to improved survival on antiretroviral therapies, yet little is known about racial differences in prostate cancer risk by HIV-infection status and age.

Methods

This is a prospective cohort study of prostate cancer risk in 2,800 HIV-infected and -uninfected men who have sex with men (MSM) aged 40–70 years (22% African American) who were enrolled in the multicenter AIDS cohort study from 1996 to 2010. Poisson regression models were used to examine associations between race and HIV-infection status and prostate cancer risk among men aged 40–70, 40–55, and 56–70 years.

Results

Among men aged 40–70 years, incidence rates (IR) per 100,000 person-years were 169 among all men and 276 among African American HIV-infected men. Prostate cancer risk was similar by HIV-infection status (IRR 1.0, 95% CI 0.55–1.82), but nearly threefold higher in African Americans compared to non-African Americans in adjusted models (IRRs 2.66 and 3.22, 95% CIs 1.36–5.18 and 1.27–8.16 for all or HIV-infected men, respectively). Racial disparity in prostate cancer risk was greatest in African American men aged 40–55 years (adjusted IRR 3.31, 95% CI 1.19–9.22). Prostate cancer risk showed associations with family history of prostate cancer (p = 0.001), but not heavy smoking, androgen supplement use, or HIV-related factors.

Conclusions

Among MSM, African American HIV-positive and HIV-negative men aged 40–55 years have threefold increased risk of young-onset prostate cancer compared to non-African American men, highlighting the need to make informed decisions about screening in this population.

     

Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HR_fixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HR_fixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HR_fixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HR_fixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.     

Coffee and tea consumption in relation to prostate cancer prognosis

Background

Bioactive compounds found in coffee and tea may delay the progression of prostate cancer.

Methods

We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer-specific outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs).

Results

The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61 % of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95 % CI: 0.20, 0.81; p for trend = 0.01). Approximately 14 % of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression.

Conclusion

Results indicate that higher pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies.     

Fruit and vegetable intake and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Several dietary factors have been studied in relation to prostate cancer; however, most studies have not reported on subtypes of fruit and vegetables or tumor characteristics, and results obtained so far are inconclusive. This study aimed to examine the prospective association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall, by grade and stage of disease, and prostate cancer death. Lifestyle information for 142,239 men participating in the European Prospective Investigation into Cancer and Nutrition from 8 European countries was collected at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow‐up time of 13.9 years, 7,036 prostate cancer cases were identified. Compared with the lowest fifth, those in the highest fifth of total fruit intake had a significantly reduced prostate cancer risk (HR = 0.91; 95% CI = 0.83–0.99; p‐trend = 0.01). No associations between fruit subtypes and prostate cancer risk were observed, except for citrus fruits, where a significant trend was found (HR = 0.94; 95% CI = 0.86–1.02; p‐trend = 0.01). No associations between total and subtypes of vegetables and prostate cancer risk were observed. We found no evidence of heterogeneity in these associations by tumor grade and stage, with the exception of significant heterogeneity by tumor grade (p_{heterogeneity}<0.001) for leafy vegetables. No significant associations with prostate cancer death were observed. The main finding of this prospective study was that a higher fruit intake was associated with a small reduction in prostate cancer risk. Whether this association is causal remains unclear.     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Blood pressure,body size and prostate cancer risk in the Swedish Construction Workers cohort

Data from prospective studies on blood pressure and prostate cancer risk are limited, and results are inconclusive. Baseline measurements of height, weight and blood pressure were available in 336,159 men in the Swedish Construction Workers cohort. During an average of 22.2 years of follow‐up, 10,002 incident cases and 2,601 fatal cases of prostate cancer were identified in National registers. For 5,219 cases, tumor characteristics were available; 2,817 tumors were classified as nonaggressive and 2,402 as aggressive. Relative risks of disease were estimated from Cox regression models, using attained age as time‐scale, and adjusting for birth year, smoking status and body mass index (BMI). Top compared to bottom quintile level of systolic or diastolic blood pressure was associated with a significant 15–20% decreased risk of incident prostate cancer (p for trend: systolic < 0.0001, diastolic = 0.3), but blood pressure was not significantly associated with risk of fatal prostate cancer. BMI was not associated with prostate cancer incidence, but was positively associated with fatal prostate cancer; men in the top quintile had a 30% increased risk (p for trend = 0.0004). The associations between blood pressure and BMI and nonaggressive tumors were similar to those of incident prostate cancer, and associations with aggressive tumors were similar to those of fatal prostate cancer. Data from our study suggest that hypertension is associated with a decreased risk of incident prostate cancer, but the explanation for this finding is unclear. Our study support a positive association between overweight and risk of fatal prostate cancer.     

Weight change and prostate cancer incidence and mortality

The relationship between obesity and prostate cancer risk has been studied extensively but with inconsistent findings, particularly for tumor aggressiveness. Few studies have investigated weight change and prostate cancer incidence or mortality. Using the Melbourne Collaborative Cohort Study, which recruited 17,045 men aged between 40 and 69 years at study entry, we investigated associations between reported weight and body mass index (BMI) at age 18 and measured at study entry, height, weight change between age 18 and study entry and prostate cancer incidence and mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. During follow-up (mean = 15 years) of 16,514 men, we ascertained 1,374 incident prostate cancers of which 410 were classified as aggressive, and 139 deaths from prostate cancer. The incidence of all prostate cancer was not associated with body size or weight change. Weight and BMI at study entry were positively associated with aggressive prostate cancer risk (HR = 1.06, 95% CI: 1.00-1.13 per 5 kg; HR = 1.27, 95% CI: 1.08-1.49 per 5 kg/m(2)) and prostate cancer mortality (HR = 1.12, 95% CI: 1.01-1.23 per 5 kg; HR = 1.49, 95% CI: 1.11-2.00 per 5 kg/m(2)). Weight gain was positively associated with prostate cancer mortality (HR = 1.13, 95% CI: 1.02-1.26 per 5 kg increment); the HR for ≥ kg weight gain between age 18 and study entry compared to <5 kg gain over this period was 1.84, 95% CI: 1.09-3.09. Higher adult weight and BMI increases the risk of aggressive prostate cancer and mortality from prostate cancer. Weight gain during adult life is associated with increased prostate cancer mortality.     

Circulating prediagnostic interleukin‐6 and C‐reactive protein and prostate cancer incidence and mortality

Interleukin‐6 (IL‐6) and C‐reactive protein (CRP) are elevated in prostate cancer patients, but the role of prediagnostic levels of these inflammatory mediators on prostate cancer outcomes is unclear. We undertook a large, prospective case‐control study to evaluate the relation between prediagnostic levels of IL‐6 and CRP and prostate cancer incidence and mortality. We also investigated the role of the IL‐6 (?174 G/C) polymorphism in relation to circulating levels of IL‐6 and CRP, as well as cancer risk and mortality. We used unconditional logistic regression that adjusted for matching factors to analyze prostate cancer risk. For analyses of prostate cancer mortality, we conducted survival analyses in cases. Because of the strong link between inflammatory markers and body mass index (BMI), we assessed interactions between BMI and plasma levels on prostate cancer outcomes. Neither IL‐6 nor CRP plasma levels varied significantly by IL‐6 genotype. Genotype was not associated with prostate cancer risk or survival. Though neither IL‐6 nor CRP was associated with prostate cancer incidence overall, we observed a statistically significant interaction between IL‐6 and BMI on prostate cancer incidence (p_interaction < 0.01). Increasing IL‐6 levels were positively associated with risk in healthy weight men, but inversely associated with risk in overweight men. Further, prediagnostic IL‐6 was associated with time to prostate cancer progression/death among healthy weight prostate cancer cases (p_trend = 0.02). Adjusted hazard ratios were 1.73 (95% CI: 0.86, 3.51) comparing the highest to lowest IL‐6 level. Our study suggests that IL‐6 may potentially be involved in the development or progression of prostate cancer. © 2008 Wiley‐Liss, Inc.     

Prostate Cancer Incidence and Mortality in Relationship to Family History of Prostate Cancer; Findings From The PLCO Trial

BackgroundThe purpose of the study was to determine the relationship between family history of prostate cancer in a first-degree relative (FDR) and prostate cancer incidence and mortality.Patients and MethodsDeidentified data sets of men recruited in the Prostate, Lung, Colorectal, and Ovary (PLCO) trial were accessed. Men with complete information about family history of prostate cancer in an FDR were included. The effect of family history on prostate cancer incidence and mortality was assessed in a multivariate Cox regression model. Likewise, the effect of the number of FDRs with prostate cancer and the effect of youngest diagnosis age of an FDR with prostate cancer were assessed.ResultsA total of 74,781 participants were included in the current analysis, including 5281 participants with family history of prostate cancer in an FDR and 69,500 participants without family history of prostate cancer in an FDR. Among participants without family history of prostate cancer in an FDR, a total of 7450 patients (10.5%) were subsequently diagnosed with prostate cancer; whereas among patients with family history of prostate cancer in an FDR, a total of 889 patients (16.5%) were subsequently diagnosed with prostate cancer. In an adjusted multivariate Cox regression model, family history of prostate cancer was associated with a higher probability of prostate cancer diagnosis (hazard ratio [HR], 1.590; 95% confidence interval [CI], 1.482-1.705; P < .001). The number of FDRs with prostate cancer proportionally correlated with higher prostate cancer incidence (HR, 1.529; 95% confidence interval [CI], 1.439-1.624; P < .001). Family history of prostate cancer in an FDR was not predictive of higher prostate cancer mortality in the PLCO screening (intervention) arm (HR, 0.829; 95% CI, 0.422-1.629; P = .587) whereas it was predictive of a higher prostate cancer mortality in the PLCO nonscreening (control) arm (HR, 1.894; 95% CI, 1.154-3.109; P = .012). Number of FDRs with prostate cancer was not associated with higher prostate cancer mortality in the PLCO screening (intervention) arm (HR, 0.956; 95% CI, 0.541-1.691; P = .878), whereas it was associated with higher prostate cancer mortality in the PLCO nonscreening (control) arm (HR, 1.643; 95% CI, 1.083-2.493; P = .020).ConclusionFamily history of prostate cancer is associated with an increased risk of prostate cancer diagnosis in the overall cohort of patients as well as a higher risk of prostate cancer mortality in the nonscreened subcohort. Further prospective assessment of the role of screening among selected high-risk populations (including those with strong family history) is warranted.     

Associations between RNA splicing regulatory variants of stemness‐related genes and racial disparities in susceptibility to prostate cancer

Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome‐wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, and two GWAS datasets of non‐Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between genetic variants of stemness‐related genes and racial disparities in susceptibility to prostate cancer. We evaluated associations of single‐nucleotide polymorphisms (SNPs) in 25 stemness‐related genes with prostate cancer risk in 1,609 cases and 2,550 controls of non‐Hispanic whites (4,934 SNPs) and 1,144 cases and 1,116 controls of African descendants (5,448 SNPs) with correction by false discovery rate ≤0.2. We identified 32 SNPs in five genes (TP63, ALDH1A1, WNT1, MET and EGFR) that were significantly associated with prostate cancer risk, of which six SNPs in three genes (TP63, ALDH1A1 and WNT1) and eight EGFR SNPs showed heterogeneity in susceptibility between these two racial groups. In addition, 13 SNPs in MET and one in ALDH1A1 were found only in African descendants. The in silico bioinformatics analyses revealed that EGFR rs2072454 and SNPs in linkage with the identified SNPs in MET and ALDH1A1 (r² > 0.6) were predicted to regulate RNA splicing. These variants may serve as novel biomarkers for racial disparities in prostate cancer risk.     

Occurrence of both bladder and prostate cancer in five cancer registries in Belgium, The Netherlands and the United Kingdom

ObjectiveTo assess the occurrence of both bladder and prostate tumours in five well defined cancer registries.MethodsAnonymous data were provided from each cancer registry on all male bladder and prostate cancers (invasive and non-invasive). Poisson regression was used to model the rate of developing the second primary tumour and generated incidence rate ratios (RRs) with 95% confidence intervals.ResultsFor bladder cancer and prostate cancer as first diagnosis, there was an excess risk to develop the second neoplasm. The RR decreased with increasing age of the patients. No effect of the initial treatment of the first neoplasm was found.ConclusionThis analysis found an excess risk to develop prostate cancer in bladder cancer patients younger than 70 years and the first year of follow-up after the diagnosis of bladder cancer. This may be due to detection bias, although a common aetiology may also be present.     

Geographic patterns of prostate cancer mortality and variations in access to medical care in the United States.

BACKGROUND: Striking geographic variation in prostate cancer death rates have been observed in the United States since at least the 1950s; reasons for these variations are unknown. Here we examine the association between geographic variations in prostate cancer mortality and regional variations in access to medical care, as reflected by the incidence of late-stage disease, prostate-specific antigen (PSA) utilization, and residence in rural counties. METHODS: We analyzed mortality data from the National Center for Health Statistics, 1996 to 2000, and incidence data from 30 population-based central cancer registries from the North American Association of Central Cancer Registries, 1995 to 2000. Ecological data on the rate of PSA screening by registry area were obtained from the 2001 Behavioral Risk Factor Surveillance System. Counties were grouped into metro and nonmetro areas according to Beale codes from the Department of Agriculture. Pearson correlation analyses were used to examine associations. RESULTS: Significant correlations were observed between the incidence of late-stage prostate cancer and death rates for Whites (r = 0.38, P = 0.04) and Blacks (r = 0.53, P = 0.03). The variation in late-stage disease corresponded to about 14% of the variation in prostate cancer death rates in White men and 28% in Black men. PSA screening rate was positively associated with total prostate cancer incidence (r = 0.42, P = 0.02) but inversely associated with the incidence of late-stage disease (r = -0.58, P = 0.009) among White men. Nonmetro counties generally had higher death rates and incidence of late-stage disease and lower prevalence of PSA screening (53%) than metro areas (58%), despite lower overall incidence rates. CONCLUSION: These ecological data suggest that 10% to 30% of the geographic variation in mortality rates may relate to variations in access to medical care.