Primary Prostate Cancer Cases Research Articles

Genetic variation in interleukin 8 and its receptor genes and its influence on the risk and prognosis of prostate cancer among Finnish men in a large cancer prevention trial

The cytokine interleukin 8 (IL-8) may play a role in the pathogenesis of prostate cancer through the modulation of tumour immune response or enhanced angiogenesis. A common polymorphism of the IL-8 (-251) gene, which may affect the production level of the cytokine, has been inversely associated with a number of diseases, including prostate cancer. We examined the most representative single nucleotide polymorphisms (SNPs) for the IL-8 and its receptors (CXCR1 and CXCR2) genes, and conducted a case-control study nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to examine if these SNPs are associated with susceptibility to and prognosis of prostate cancer. Using incidence density sampling, 584 cases of primary prostate cancer and 584 matched controls were selected. In this population, we observed no strong association between the SNPs for IL-8 -251 (A-->T), CXCR1 +860 (C-->G) and CXCR2 -1010 (A-->G) and either the subsequent risk of prostate cancer or individual prognostic factors among cases. Although none of the SNPs studied are likely to have major effects on prostate cancer susceptibility, a role for other polymorphisms associated within these genes cannot be excluded.

Dietary patterns and risk of prostate cancer in Ontario, Canada

Dietary patterns reflect combinations of dietary exposures, and here we examine these in relation to prostate cancer risk. In a case-control study, 80 incident primary prostate cancer cases and 334 urology clinic controls were enrolled from 1997 through 1999 in Kingston, Ontario, Canada. Food-frequency questionnaires were completed prior to diagnosis and assessed intake in the 1-year period 2-3 years prior to enrollment. Among controls, dietary intake was used in principal components analyses to identify patterns that were then evaluated with all subjects in relation to prostate cancer risk using unconditional logistic regression, controlling for age. Four dietary patterns were identified: Healthy Living, Traditional Western, Processed and Beverages. Increased prostate cancer risk is apparent in relation to the Processed pattern, composed of processed meats, red meats, organ meats, refined grains, white bread, onions and tomatoes, vegetable oil and juice, soft drinks and bottled water. The OR for the highest tertile compared to baseline is 2.75 (95% CI 1.40-5.39), with a dose-response pattern (trend test p < 0.0035). Our results suggest that a dietary pattern including refined grain products, processed meats and red and organ meats contributes to increased prostate cancer risk. Since dietary information was collected before subjects knew their diagnosis, recall bias was avoided.

CD24 expression is a significant predictor of PSA relapse and poor prognosis in low grade or organ confined prostate cancer.

The prognostic impact of tumor grading and staging is markedly reduced in organ confined or moderately differentiated prostate cancer, which underscores the importance of new prognostic markers. Evaluating public expression data of prostate cancer, we found an upregulation of the candidate gene CD24. We examined immunohistochemically the expression of CD24 protein in 31 nodal metastases and 102 adenocarcinomas of the prostate and correlated our findings to clinicopathological parameters. CD24 expression was found in 48% of primary prostate cancer cases and in 68% of lymph node metastases. Kaplan Meier curves and Cox regression analysis showed that CD24 expression was strongly linked to significantly earlier disease progression (relative risk = 3.2), which was especially pronounced in organ confined, or moderately differentiated primary prostate tumors. We conclude that CD24 is an important prognostic tissue marker for prostate cancer which could help to define patients of low or high risk of recurrence.

Reduced risk of prostate cancer among patients with diabetes mellitus

Although diabetes mellitus is associated with an increased risk of several malignancies, a negative association with prostate cancer is biologically most plausible. The epidemiologic evidence is, however, inconsistent, limited and based mostly on small studies. We present results from a large, population-based cohort study in Sweden, where we assessed prostate cancer risk among patients hospitalized for diabetes mellitus. The cohort was composed of patients identified in the Swedish In-Patient Register as having a hospital discharge diagnosis of diabetes mellitus in 1965-1994. The follow-up was done by linkages with the national cancer register and other population-based registers. Standardized incidence ratios (SIRs), with 95% confidence interval (CI), were used as a measure of relative risk. After complete exclusion of the first year of follow-up (to avoid selection bias), 135,950 men remained in the cohort, contributing 827,099 years of follow-up to the study. A total of 2,455 incident cases of primary prostate cancer were identified during 1-31 years of follow-up, yielding an overall SIR of 0.91 (95% CI 0.87-0.94); this risk reduction was more pronounced among patients who have been hospitalized for diabetic complications (SIR = 0.82; 95% CI 0.74-0.91). We found no consistent trends in risk related to age at first hospitalization or to duration of follow-up. We did find a small, but significantly decreased risk of prostate cancer among men who had been hospitalized for diabetes mellitus.

Expression of human GIPC1 in normal tissues, cancer cell lines, and primary tumors

GIPC1/RGS19IP1/GIPC, GIPC2, and GIPC3 are a family of central PDZ-domain proteins with GH1 and GH2 domains. GIPC1 interacts with GTPase-activating protein RGS19/RGS-GAIP, TGFbeta type III receptor, receptor tyrosine kinase TrkA, and integrin alpha6A subunit. Xenopus homologue of human GIPCs interacts with Frizzled-3 class of WNT receptor. We investigated expression of human GIPC1 mRNA in normal tissues, cancer cell lines, and primary tumors. GIP1A probe (nucleotide position 1075-1483 of GIPC1 cDNA) hybridized to GIPC1 mRNA of 1.8 kb in size. GIPC1 mRNA was almost ubiquitously expressed in various normal tissues. Expression level of GIPC1 mRNA was relatively lower in bone marrow and peripheral blood leukocytes. GIPC1 mRNA was relatively highly expressed in gastric cancer cell lines OKAJIMA, TMK1, MKN28, MKN45, MKN74, KATO-III, pancreatic cancer cell line AsPC-1, colorectal cancer cell line SW480, and lung cancer cell line A549. On the other hand, GIPC1 mRNA was almost undetectable in leukemia/lymphoma cell lines HL-60, Raji, and Daudi. Expression of GIPC1 mRNA was down-regulated in 12 out of 14 cases of primary kidney tumors, 10 out of 18 cases of primary colorectal tumors, 3 out of 8 cases of primary gastric cancer, 3 out of 3 cases of primary prostate cancer. Because GIPC1 induces increased expression of TGFbeta type III receptor at the cell surface and enhanced responsiveness to TGFbeta, down-regulation of GIPC1 mRNA in tumors might promote cellular proliferation through interference of TGFbeta signaling.

A prospective cohort study on consumption of alcoholic beverages in relation to prostate cancer incidence (The Netherlands).

To examine alcohol consumption in relation to prostate cancer incidence in the Netherlands Cohort Study. At baseline in 1986, 58,279 men aged 55-69 years completed a self-administered questionnaire on diet, consumption of alcoholic beverages and other risk factors for cancer. For data processing and analyses the case-cohort approach was used. After 6.3 years of follow-up, 680 incident primary prostate cancer cases were available for analysis. In multivariate analyses adjusted for age, socioeconomic status and family history of prostate cancer, no association between total alcohol consumption, alcohol intake from beer and liquor and prostate cancer risk was found. Increased associations were found for alcohol from white wine and fortified wines compared to nondrinkers, but not for red wine. The RRs (95% CI) in the intake category of > or = 15 g/day were 3.3 (1.2-9.2) and 2.3 (1.2-4.7), respectively, after additional adjustment for total alcohol intake. There was, however, no significant trend in risk. Alcohol intake was more strongly related with localized than with advanced prostate tumors. Our results do not support an important role for alcohol in prostate cancer etiology. Nevertheless, for specific types of alcoholic beverages, particularly wines, a positive association was suggested which needs examination in further studies.