Non-steroidal anti-inflammatory drug use and prostate cancer in a high-risk population.

Animal and laboratory studies suggest that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce prostate cancer risk. The aim of this study was to investigate the association between NSAID use and prostate cancer in a high-risk population. We included 1299 men who were referred to our university's prostate cancer detection clinic for prostate biopsy between January 1999 and July 2003. Before transrectal ultrasonography and prostate biopsy, all men completed a self-administered questionnaire that included questions on drug use in the preceding 5 years. On average, NSAID users were older than non-users but there was no significant difference in mean baseline prostate-specific antigen (PSA). Four hundred and ninety-four (38%) had biopsy-confirmed prostate cancer. After adjustment for age, family history of prostate cancer and other potential confounders, use of aspirin was associated with a 42% reduction in the odds of prostate cancer detection [95% confidence interval (CI) 0.36-0.91]. Among cases, regular use of NSAIDs was inversely related to the risk of detection of more poorly differentiated cancers and cancers with higher percentage core involvement. These findings support other epidemiological and experimental evidence that suggests that aspirin may be useful in prostate cancer prevention. Further observational studies with adequate case definition and exposure measurements and careful adjustment for detection bias are warranted.     

Serum calcium and incident and fatal prostate cancer in the National Health and Nutrition Examination Survey

We examined the association between serum calcium levels and the risk for prostate cancer using a prospective cohort, the National Health and Nutrition Examination Survey (NHANES) and the NHANES Epidemiologic Follow-up Study. Eighty-five incident cases of prostate cancer and 25 prostate cancer deaths occurred over 46,188 person-years of follow-up. Serum calcium was determined an average of 9.9 years before the diagnosis of prostate cancer. Comparing men in the top with men in the bottom tertile of serum calcium, the multivariable-adjusted relative hazard for fatal prostate cancer was 2.68 (95% confidence interval, 1.02-6.99; P(trend) = 0.04). For incident prostate cancer, the relative risk for the same comparison was 1.31 (95% confidence interval, 0.77-2.20; P(trend) = 0.34). These results support the hypothesis that high serum calcium or a factor strongly associated with it (e.g., high serum parathyroid hormone) increases the risk for fatal prostate cancer. Our finding of a >2.5-fold increased risk for men in the highest tertile of serum calcium is comparable in magnitude with the risk associated with family history and could add significantly to our ability to identify men at increased risk for fatal prostate cancer.     

Cimetidine and other histamine2-receptor antagonist use in relation to risk of breast cancer.

OBJECTIVE: Cimetidine, a histamine2-receptor antagonist (H2 blocker) commonly used to treat symptoms of peptic and duodenal ulcer, influences both hormonal and immune pathways. We investigated the influence of cimetidine use on the risk of breast cancer in our hospital-based case control surveillance study. METHODS: Data on medication use and other factors were elicited from patients admitted to hospitals from 1977 to 2002. We compared 6,994 breast cancer cases with a control group comprising cancer (n = 2,478) and noncancer (n = 6,004) diagnoses. Conditional logistic regression models were used to estimate odds ratios for H2 blocker use that began at least 1 year prior to admission. Regular use was defined as use for at least 4 days per week for at least 3 continuous months. RESULTS: The odds ratio for breast cancer among regular users of cimetidine was 0.9 (95% confidence interval, 0.6-1.2) using a combined cancer and noncancer control group. For use of 4 or more years' duration, the odds ratio was < 1.0 but was not statistically significant. The odds ratio for the regular use of other H2 blockers was 0.9 (95% confidence interval, 0.6-1.3). CONCLUSIONS: Our data agree with data from three prior studies which indicate that cimetidine is not associated with the risk of breast cancer. Other H2 blockers were also unrelated to the risk of breast cancer.     

Prostate cancer risk among users of finasteride and alpha-blockers - a population based case-control study

Finasteride has been reported to reduce prostate cancer risk in asymptomatic men. However, in clinical practice finasteride and alpha-blockers are used to treat benign prostatic hyperplasia (BPH). We evaluated prostate cancer risk among users of BPH pharmacotherapy at the population level. Comprehensive Finnish national registries provided information on 24723 prostate cancer cases and controls. Overall, prostate cancer risk was elevated among users of both drug categories compared to non-users (odds ratio, OR=1.41; 95% confidence interval, CI 1.31-1.51 for finasteride and OR=1.79; 95% CI 1.67-1.91 for alpha-blockers). However, the risk was lower among finasteride users when compared with alpha-blocker users (OR=0.80; 95% CI 0.64-1.00). Regular finasteride users had the lowest risk. The increased risk is probably due to enhanced diagnostics of prostate cancer in men with BPH. Finasteride use does not decrease prostate cancer incidence compared with non-users. Nevertheless, the risk is lower when compared with alpha-blocker users.     

Family history and environmental risk factors for colon cancer.

BACKGROUND: We analyzed the joint effect of environmental risk factors and family history of colorectal cancer on colon cancer. METHODS: We used data from a case-control study conducted in northern Italy between 1992 and 1996 including 1225 cases with colon cancer and 4154 controls. We created a weighed risk factor score for the main environmental risk factors in this population (positive family history, high education, low occupational physical activity, high daily meal frequency, low intake of fiber, low intake of calcium, and low intake of beta-carotene). RESULTS: Compared with the reference category (subjects with no family history of colorectal cancer and in the lowest tertile of the risk factor score), the odds ratios of colon cancer were 2.27 [95% confidence interval (CI) = 1.89-2.73] for subjects without family history and in the highest environmental risk factor score, 3.20 (95% CI = 2.05-5.01) for those with family history and low risk factor score, and 7.08 (95% CI = 4.68-10.71) for those with family history and high risk factor score. The pattern of risk was similar for men and women and no meaningful differences emerged according to subsite within the colon. CONCLUSIONS: Family history of colorectal cancer interacts with environmental risk factors of colon cancer.     

Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors

Genetic factors may be used not only to assess risk of prostate cancer development but also to evaluate prostate cancer outcomes including clinical prognosis, treatment methods, and treatment response. To assess the role of family history on prostate cancer outcomes, we evaluated tumor characteristics, diagnostic precursors and biochemical (prostate specific antigen) relapse-free survival in men with and without a family history of prostate cancer. A total of 684 prostate cancer cases unselected for family history were identified from an ongoing hospital based prostate cancer case-control study between 1995 and 2002. Self-reported family history was grouped within the following categories: none, any, moderate (one affected first or second degree relative) and high (2 or more affected first or second degree relatives). We further considered groups defined by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor stage was not significantly associated with any (odds ratio [OR] = 1.43 95% confidence interval [CI] = 1.00-2.05) or moderate (OR = 1.48, 95% CI = 1.0-2.19) family histories. Men diagnosed before age 60, however, had higher tumor stages if they had any (OR = 2.19, 95% CI = 1.28-3.75) or moderate (OR = 2.15, 95% CI = 1.2-3.9) family histories. Men diagnosed after age 60 with any family history were significantly more likely to experience biochemical (PSA) failure (Hazard ratio [HR] = 2.60, 95%CI = 1.08-6.25). Men with any and moderate family histories were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI = 1.25-4.95 and HR = 2.46, 95% CI = 1.17-5.16, respectively). Moderate family history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI = 1.06-4.34). Our results suggest that a family history of prostate cancer may be associated with predictors of clinical outcome in prostate cancer cases unselected for a family history of prostate cancer.     

Zinc supplement use and risk of prostate cancer

The high concentration of zinc in the prostate suggests that zinc may play a role in prostate health. We examined the association between supplemental zinc intake and prostate cancer risk among 46 974 U.S. men participating in the Health Professionals Follow-Up Study. During 14 years of follow-up from 1986 through 2000, 2901 new cases of prostate cancer were ascertained, of which 434 cases were diagnosed as advanced cancer. Supplemental zinc intake at doses of up to 100 mg/day was not associated with prostate cancer risk. However, compared with nonusers, men who consumed more than 100 mg/day of supplemental zinc had a relative risk of advanced prostate cancer of 2.29 (95% confidence interval = 1.06 to 4.95; P(trend) =.003), and men who took supplemental zinc for 10 or more years had a relative risk of 2.37 (95% confidence interval = 1.42 to 3.95; P(trend)<.001). Although we cannot rule out residual confounding by supplemental calcium intake or some unmeasured correlate of zinc supplement use, our findings, that chronic zinc oversupply may play a role in prostate carcinogenesis, warrant further investigation.     

Risk Factors of Prostate Cancer: a Case-control Study in Faisalabad,Pakistan

Background: Prostate cancer is the third most commonly diagnosed cancer among males in Pakistan but verylittle is known about risk factors among the Pakistani population. Therefore a hospital-based, case-control studywas carried out in Faisalabad to identify potential risk factors. Materials and Methods: This study was basedon 140 prostate cancer cases and 280 normal controls. Logistic regression was used to estimate odds ratios and95% confidence intervals for odds ratios to assess the relationship between prostate cancer and different riskfactors. Results: Family history of prostate cancer, age, smoking, obesity, consumption of red meat and frequentuse of fat items significantly increased the prostate cancer risk (odds ratios and 95% confidence intervals of:7.32; 1.79-29.8; 16.9, 5.60-50.8; 2.47, 1.17-5.18; 5.79, 2.66-12.6; 2.71, 1.07-6.91; and 3.39, 1.47-7.83, respectively.On the other hand, more consumption of fruit, fluid intake and better lifestyle (physical activity) significantlyreduced the risk of developing prostate cancer with odd ratios and corresponding 95% confidence intervals of:0.27, 0.11-0.61; 0.05, 0.02-0.12; and 0.28, 0.13- 0.58. Conclusions: The results of the present study suggested thatage, family history of prostate cancer, smoking, obesity, fluid intake, frequent use of fat items, consumption offruits and better lifestyle might be associated with prostate cancer among Pakistani males.     

Confirmation of a positive association between prostate cancer risk and a locus at chromosome 8q24.

BACKGROUND: Family-based linkage studies, association studies, and studies of tumors have highlighted human chromosome 8q as a genomic region of interest for prostate cancer susceptibility loci. Recently, a locus at 8q24, characterized by both a single nucleotide polymorphism (SNP) and a microsatellite marker, was shown to be associated with prostate cancer risk in Icelandic, Swedish, and U.S. samples. Although the data were provocative, the U.S. samples were not population based, which precludes assessment of the potential contribution of this locus to prostate cancer incidence in the United States. METHODS: We analyzed both markers in a population-based, case-control study of middle-aged men from King County, Washington. RESULTS: Overall, there was a significant positive association between the A allele of the SNP rs1447295 and prostate cancer risk [odds ratio, 1.4; 95% confidence interval (95% CI), 1.1-2.0] but no significant association with the microsatellite DG8S737. However, significant associations were observed for both markers in men with high Gleason scores. Adjusting for age, first-degree family history of prostate cancer, and prostate cancer screening history, the adjusted odds ratios were 1.4 (95% CI, 1.1-1.8) for the A allele of the SNP and 1.9 (95% CI, 1.2-2.8) for the -10 allele of the microsatellite. CONCLUSIONS: These data suggest that the locus on chromosome 8q24 harbors a genetic variant associated with prostate cancer and that the microsatellite marker is a stronger risk factor for aggressive prostate cancers defined by poorly differentiated tumor morphology.     

A population-based survey of complementary and alternative medicine use in men recently diagnosed with prostate cancer

PURPOSE: To determine prevalence and patterns of use of complementary and alternative medicine (CAM) among men recently diagnosed with prostate cancer. STUDY DESIGN: Men, diagnosed with prostate cancer over a 10-month period in British Columbia, Canada, were randomly selected to obtain a population-based sample. METHODS: Surveys, addressing patient demographics, types of CAM therapies, and CAM information resources utilized, reasons for use, and disclosure to physician(s), were mailed to 1108 men newly diagnosed with prostate cancer. A 42% response rate was obtained. RESULTS: Thirty-nine percent of patients used CAM therapies with the most common being herbal supplements (saw palmetto), vitamins (vitamin E), and minerals (selenium). The most common reasons given for choosing to use CAM therapies were to (1) boost the immune system and (2) prevent recurrence. The majority of men (58%) had told their physician(s) about their CAM use, but few utilized either their family physician (15%) or their oncologist (7%) as sources of CAM information. CAM users most commonly consulted friends or family (39%) or the Internet (19%) for information about CAM. CAM users were more likely than nonusers to delay (9%) or decline (4%) conventional treatment. Respondents who had never used CAM had typically never thought about it or did not have enough information about the treatments. CONCLUSIONS: More than one third of recently diagnosed prostate cancer patients utilize some form of CAM therapy, and the majority disclose their use to their physician(s). However, they tend to rely on anecdotal information for their CAM decision making. Dissemination of reliable CAM information is one key to helping men navigate this difficult arena.     

Cyp17 promoter variant associated with prostate cancer aggressiveness in African Americans.

Androgens play an important role in the etiology of prostate cancer. The CYP17 gene encodes the cytochrome P450c17alpha enzyme, which is the rate-limiting enzyme in androgen biosynthesis. A T to C polymorphism in the 5' promoter region has recently been associated with prostate cancer. However, contradictory data exists concerning the risk allele. To investigate further the involvement of the CYP17 variant with prostate cancer, we typed the polymorphism in three different populations and evaluated its association with prostate cancer and clinical presentation in African Americans. We genotyped the CYP17 polymorphism in Nigerian (n = 56), European-American (n = 74), and African-American (n = 111) healthy male volunteers, along with African-American men affected with prostate cancer (n = 71), using pyrosequencing. Genotype and allele frequencies did not differ significantly across the different control populations. African-American men with the CC CYP17 genotype had an increased risk of prostate cancer (odds ratio, 2.8; 95% confidence interval, 1.0-7.4) compared with those with the TT genotype. A similar trend was observed between the homozygous variant genotype in African-American prostate cancer patients and clinical presentation. The CC genotype was significantly associated with higher grade and stage of prostate cancer (odds ratio, 7.1; 95% confidence interval, 1.4-36.1). The risk did not differ significantly by family history or age. Our results suggest that the C allele of the CYP17 polymorphism is significantly associated with increased prostate cancer risk and clinically advanced disease in African Americans.     

Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer.

BACKGROUND: Although several previous case-control studies have investigated associations between sexually transmitted infections (STI) and prostate cancer, most have focused on gonorrhea and syphilis, two well-recognized, symptomatic STIs. Another STI of interest for prostate carcinogenesis is trichomonosis, a less well recognized and frequently asymptomatic STI with known prostate involvement. We investigated this infection in relation to incident prostate cancer in a nested case-control study within the Health Professionals Follow-up Study. METHODS: Prostate cancer cases were men diagnosed with prostate cancer between the date of blood draw (1993-1995) and 2000 (n = 691). Controls were men who had had at least one prostate-specific antigen test and who were free of prostate cancer and alive at the time of case diagnosis. One control was individually matched to each case by age (n = 691). Serologic evidence of a history of trichomonosis was assessed by a recombinant Trichomonas vaginalis alpha-actinin IgG ELISA. RESULTS: Thirteen percent of cases and 9% of controls were seropositive for trichomonosis (adjusted odds ratio, 1.43; 95% confidence interval, 1.00-2.03). This association persisted after additional adjustment for such factors as a history of other STIs, and was strongest among men who used aspirin infrequently over the course of their lives (odds ratio, 2.05; 95% confidence interval, 1.05-4.02, P(interaction) = 0.11). CONCLUSIONS: Serologic evidence of a history of trichomonosis was positively associated with incident prostate cancer in this large, nested case-control study of male health professionals. As this study is the first, to our knowledge, to investigate associations between T. vaginalis serology and prostate cancer, additional studies are necessary before conclusions can be made.     

Vasectomy and risk of prostate cancer.

Most studies do not support an association between vasectomy and prostate cancer, but a few have suggested a link. Vasectomy is a common birth control method, and prostate cancer is the most frequently diagnosed solid tumor in men, making this a major public health question. This study was specifically designed to determine whether or not vasectomy is associated with risk of prostate cancer. To examine this issue, we conducted a population-based case-control study in King County, Washington. Interviews were completed with men ages 40-64 years newly diagnosed with prostate cancer between January 1993 and December 1996 who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry (n = 753) and with comparison men without prostate cancer identified from the same general population (n = 703). The odds ratio (OR) for prostate cancer in relation to vasectomy was assessed. The prevalence of vasectomy was similar in cases (39.4%) and controls (37.7%), resulting in no association (adjusted OR, 1.10; 95% confidence interval, 0.9-1.4). There was no consistent evidence that risk varied by the age at which vasectomy was performed, the time since vasectomy, or the calendar period when the vasectomy was performed. The OR in relation to vasectomy was higher in men with less aggressive prostate cancer. Risk estimates did not differ according to age, race, or family history of prostate cancer. This study suggests that vasectomy is not associated with the risk of developing prostate cancer. It also provides evidence that vasectomized men may be more likely to present with earlier-stage, lower-grade prostate tumors.     

Family history of cancer and the risk of prostate cancer and benign prostatic hyperplasia

We analysed the relation between family history of cancer in first-degree relatives and risk of prostate cancer (PC) and benign prostatic hyperplasia (BPH) using data from a multicentric case-control study conducted in Italy from 1991 to 2002 on 1,294 cases of incident, histologically confirmed PC, 1,369 cases of BPH and 1,451 men admitted to the same network of hospitals for acute, nonneoplastic conditions. Unconditional logistic regression was used to estimate odds ratios (OR) of PC and BPH, adjusted for age and other confounders. Men with a family history of PC had an OR of PC of 4.0 (95% confidence interval [CI] 2.5-6.5), and the risk was higher when the proband was younger, when 2 or more relatives were affected or when the affected relative was a brother. The risk of PC was also increased in men with a family history of cancer of the ovary (OR = 6.2, 95% CI 1.2-32), bladder (OR = 3.5, 95% CI 1.6-7.4) and kidney (OR = 3.1, 95% CI 1.1-8.5). An involvement of breast/ovarian cancer predisposition genes in a small proportion of PCs was suggested by the cluster of these cancers in female relatives of a few PC cases. The risk of BPH was increased in men with a family history of bladder cancer (OR = 2.2, 95% CI 1.0-5.0) but not PC (OR = 1.2, 95% CI 0.7-2.2). Our study adds further information on the association of family history of cancer and risk of PC and is, to our knowledge, the first comprehensive epidemiologic information on family history of cancer and risk of BPH.