@article {666, title = {Hypertension, heart rate, use of antihypertensives, and incident prostate cancer.}, journal = {Ann Epidemiol}, volume = {11}, year = {2001}, month = {2001 Nov}, pages = {534-42}, abstract = {

PURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth.

METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants.

RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95\% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95\% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk.

CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.

}, keywords = {Aged, Antihypertensive Agents, Cohort Studies, Heart Rate, Humans, Hypertension, Incidence, Male, Proportional Hazards Models, Prostatic Neoplasms, Risk, United States}, issn = {1047-2797}, doi = {10.1016/s1047-2797(01)00246-0}, author = {Fitzpatrick, A L and Daling, J R and Furberg, C D and Kronmal, R A and Weissfeld, J L} } @article {810, title = {Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin.}, journal = {Cancer}, volume = {103}, year = {2005}, month = {2005 Jan 01}, pages = {76-84}, abstract = {

BACKGROUND: There have been several epidemiologic studies investigating the association between circulating levels of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case-control study within the Cardiovascular Health Study cohort.

METHODS: In men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n=174), the levels of IGF-I, IGFBP-3, and insulin were measured on blood samples that were obtained 1-9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age.

RESULTS: Relative to the men with IGF-I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95\% confidence interval [95\% CI], 0.43-1.38), 0.73 (95\% CI, 0.41-1.30), and 0.67 (95\% CI, 0.37-1.25), respectively. The results were influenced little by adjustment for levels of IGFBP-3 or, instead, by evaluating the molar IGF-I/IGFBP-3 ratio. An analysis that was restricted to men who had plasma prostate-specific antigen levels <4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP-3 were 0.91 (95\% CI, 0.49-1.68), 0.47 (95\% CI, 0.25-0.94), and 0.65 (95\% CI, 0.35-1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical.

CONCLUSIONS: The IGF-I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP-3 level was associated with a modest decrease in risk.

}, keywords = {Aged, Aged, 80 and over, Carcinoma, Case-Control Studies, Humans, Hypoglycemic Agents, Incidence, Insulin, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Prostatic Neoplasms, Risk Factors}, issn = {0008-543X}, doi = {10.1002/cncr.20727}, author = {Chen, Chu and Lewis, S Kay and Voigt, Lynda and Fitzpatrick, Annette and Plymate, Stephen R and Weiss, Noel S} } @article {883, title = {Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its Interaction with the Androgen Receptor (United States).}, journal = {Cancer Causes Control}, volume = {17}, year = {2006}, month = {2006 Mar}, pages = {187-97}, abstract = {

OBJECTIVE: To determine whether directly observed prostate-specific antigen (PSA) promoter diploid haplotype, either alone or in conjunction with androgen receptor (AR) genotype, is associated with prostate cancer risk.

METHODS: We conducted a case-control study nested within the US population-based Cardiovascular Health Study cohort. Incident prostate cancers were identified by linkage to cancer registry records for the years 1989-2000. We genotyped 193 cases and 391 controls for the PSA -252 G/A and -158 G/A SNPs and the AR CAG microsatellite, and developed methods to directly determine proximal PSA promoter haplotypes. Exact logistic regression was used to estimate odds ratios and significance levels.

RESULTS: No significant associations were observed between PSA diplotype and prostate cancer overall. Short (< 20) AR CAG repeat lengths were associated with modest increases in the risk of prostate cancer (OR, 1.46; 95\% CI, 0.97-2.19; p = 0.071) that were significant for advanced disease (OR, 1.82; 95\% CI, 1.02-3.26; p = 0.044). Men who possessed two copies of the PSA*2 (-252G/-158G) haplotype and short AR CAG repeat lengths had a 4-fold (95\% CI, 1.05-20.75; exact p = 0.040) increased risk of prostate cancer, and a 7-fold (95\% CI, 1.25-39.78; exact p = 0.026) increased risk of advanced disease.

CONCLUSIONS: We found evidence that the PSA*2*2 diplotype in combination with short AR CAG alleles increases a man{\textquoteright}s risk of developing prostate cancer. These findings support an etiologic role in prostate cancer of genetic interactions between polymorphisms that increase AR transactivation strength and those that alter the regulatory regions of target genes such as PSA that are responsive to androgen stimulation.

}, keywords = {Aged, Biomarkers, Tumor, Case-Control Studies, Cohort Studies, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Polymorphism, Genetic, Prostate-Specific Antigen, Prostatic Neoplasms, Receptors, Androgen, United States}, issn = {0957-5243}, doi = {10.1007/s10552-005-0454-8}, author = {Sieh, Weiva and Edwards, Karen L and Fitzpatrick, Annette L and Srinouanprachanh, Sengkeo L and Farin, Fred M and Monks, Stephanie A and Kronmal, Richard A and Eaton, David L} } @article {1055, title = {Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies.}, journal = {Ann Intern Med}, volume = {149}, year = {2008}, month = {2008 Oct 07}, pages = {461-71, W83-8}, abstract = {

BACKGROUND: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer.

PURPOSE: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer.

DATA SOURCES: Studies identified in PubMed, Web of Science, and CancerLit.

STUDY SELECTION: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate.

DATA EXTRACTION: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom.

DATA SYNTHESIS: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95\% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake.

LIMITATIONS: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies.

CONCLUSION: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.

}, keywords = {Aged, Humans, Insulin-Like Growth Factor Binding Protein 2, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Male, Middle Aged, Prospective Studies, Prostatic Neoplasms, Risk Factors, Somatomedins}, issn = {1539-3704}, doi = {10.7326/0003-4819-149-7-200810070-00006}, author = {Roddam, Andrew W and Allen, Naomi E and Appleby, Paul and Key, Timothy J and Ferrucci, Luigi and Carter, H Ballentine and Metter, E Jeffrey and Chen, Chu and Weiss, Noel S and Fitzpatrick, Annette and Hsing, Ann W and Lacey, James V and Helzlsouer, Kathy and Rinaldi, Sabina and Riboli, Elio and Kaaks, Rudolf and Janssen, Joop A M J L and Wildhagen, Mark F and Schr{\"o}der, Fritz H and Platz, Elizabeth A and Pollak, Michael and Giovannucci, Edward and Schaefer, Catherine and Quesenberry, Charles P and Vogelman, Joseph H and Severi, Gianluca and English, Dallas R and Giles, Graham G and Stattin, P{\"a}r and Hallmans, G{\"o}ran and Johansson, Mattias and Chan, June M and Gann, Peter and Oliver, Steven E and Holly, Jeff M and Donovan, Jenny and Meyer, Fran{\c c}ois and Bairati, Isabelle and Galan, Pilar} } @article {1084, title = {C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older.}, journal = {Cancer Causes Control}, volume = {20}, year = {2009}, month = {2009 Sep}, pages = {1193-203}, abstract = {

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95\% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation.

}, keywords = {African Americans, Aged, Aged, 80 and over, Biomarkers, C-Reactive Protein, European Continental Ancestry Group, Humans, Inflammation, Interleukin-6, Male, Polymorphism, Single Nucleotide, Prospective Studies, Prostatic Neoplasms, Risk Factors}, issn = {1573-7225}, doi = {10.1007/s10552-009-9320-4}, author = {Pierce, Brandon L and Biggs, Mary L and DeCambre, Marvalyn and Reiner, Alexander P and Li, Christopher and Fitzpatrick, Annette and Carlson, Christopher S and Stanford, Janet L and Austin, Melissa A} }