To describe recent epidemiologic trends in stage IV prostate cancer. Although advances in screening and diagnostic techniques have led to earlier detection of prostate cancer, a portion of patients still present with late-stage disease.
Population-based cancer registry data from the Surveillance, Epidemiology, and End Results Program (cases from 1988 to 2003, follow-up through 2005) were used to calculate annual age-adjusted incidence rates of stage IV prostate cancer (overall and for the subset presenting with distant metastases) and to assess time trends in patient, tumor, and treatment characteristics and survival.
From 1988 to 2003, the age-adjusted incidence of stage IV prostate cancer significantly declined by 6.4% each year. The proportion of men diagnosed at younger ages, with poorly differentiated tumors, or who underwent a radical prostatectomy significantly increased over time. Five-year relative survival improved across the study period (from 41.6% to 62.3%), particularly in those diagnosed at younger ages or with moderately to well-differentiated tumors. Later years of diagnosis were independently associated with a decreased risk of death (from all causes and from prostate cancer specifically) after controlling for important patient, tumor, and treatment characteristics. Tumor grade and receipt of radical prostatectomy appeared to be the strongest independent prognostic indicators. Temporal trends were similar in the subset presenting with distant metastases, except that no significant improvement in survival was observed.
As younger men may expect to live longer with advanced prostate cancer, there remains a need to widen the range of therapeutic and supportive care options.
Obesity is a risk factor for renal cell (or renal) cancer. The increasing prevalence of obesity may be contributing to the rising incidence of this cancer over the past several decades. The effects of early-age obesity and change in body mass index (BMI) on renal cancer have been studied less thoroughly, and the influence of race has never been formally investigated.
Using data gathered as part of a large case-control study of renal cancer (1,214 cases and 1,234 controls), we investigated associations with BMI at several time points, as well as with height. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression modeling. Race- and sex-stratified analyses were conducted to evaluate subgroup differences.
Obesity (BMI ≥ 30 kg/m2) early in adulthood (OR=1.6 [95% CI=1.1 to 2.4]) and 5 years before diagnosis (1.6 [1.1 to 2.2]) was associated with renal cancer. The association with early-adult obesity was stronger among whites than blacks (Test for interaction, P=0.006), while the association with obesity near diagnosis was marginally stronger in women than men (Test for interaction, P=0.08). The strongest association with renal cancer was observed for obese whites both in early adulthood and prior to interview (2.6 [1.5 to 4.4]); this association was not present among blacks. Estimates of the annual excess rate of renal cancer (per 100,000 persons) attributed to both overweight and obesity (BMI > 25 kg/m2) ranged from 9.9 among black men to 5.6 among white women.
Obesity, both early and later in life, is associated with an increased risk of renal cancer. The association with early obesity appears to be stronger among whites than blacks.
The survival of men diagnosed with prostate cancer has improved over time, and the current 10-year relative survival rate is 99.7%. The long survival of patients with this common cancer raises questions about the risk of a second primary cancer and the need for continued surveillance.
A population-based cohort of 441,504 men who were diagnosed with prostate cancer between 1992 and 2010 was identified from Surveillance, Epidemiology and End Results Program (SEER) data (SEER13). The standardized incidence ratio (SIR) was calculated as an estimate of the risk of a second primary malignancy based on the incidence in the general population.
Prostate cancer survivors had a lower risk of being diagnosed with another cancer overall compared with the US population (SIR = 0.60; 95% confidence interval, 0.60–0.61). The risks of leukemia and cancers of the oral cavity and pharynx, esophagus, stomach, colon and rectum, liver, gallbladder, pancreas, lung and bronchus, and larynx were significantly lower. Conversely, these patients had a greater risk of bladder, kidney, and endocrine and soft tissue cancers. Men who received treatment with radiation therapy (external-beam radiation therapy) had long-term increases in their risk of bladder cancer (SIR = 1.42) and rectal cancer (SIR = 1.70) risk compared with who did not receive radiation (SIRbladder = 0.76; SIRrectal = 0.74). There were significant racial differences in the risk of being diagnosed with a second primary cancer, and the magnitude and direction of these risks depended on tumor type.
Prostate cancer survivors remain at risk of subsequent malignancies, and race and treatment choice important determinants of long-term risk.
prostate cancer; SEER; epidemiology; multiple primaries
Metabolic syndrome refers to a set of conditions that increases the risk of cardiovascular disease and has been associated with an increased risk of prostate cancer, particularly among African American men. This study aimed to estimate the association of metabolic syndrome with biochemical recurrence (BCR) in a racially diverse population. Among 383 radical prostatectomy patients, 67 patients had documented biochemical recurrence. Hypertension was significantly, positively associated with the rate of BCR (hazard ratio (HR) = 2.1; 95% CI = 1.1, 3.8). There were distinct racial differences in the prevalence of individual metabolic syndrome components; however, the observed associations with BCR did not differ appreciably by race. We conclude that hypertension may contribute to a poorer prognosis in surgically treated prostate cancer patients. Our findings suggest that targeting components of the metabolic syndrome which are potentially modifiable through lifestyle interventions may be a viable strategy to reduce risk of BCR in prostate cancer.
Adiponectin is a protein derived from adipose tissue suspected to play an important role in prostate carcinogenesis. Variants in the adiponectin gene (ADIPOQ) and its type I receptor (ADIPOR1) have been recently linked to risk of both breast and colorectal cancer. Therefore, we set out to examine the relationship between polymorphisms in these genes, obesity and prostate cancer in study of African American men.
Ten single nucleotide polymorphisms (SNPs) in ADIPOQ and ADIPOR1 were genotyped in DNA samples from 131 African American prostate cancer cases and 344 controls participating in the Flint Men's Health Study. Logistic regression was then used to estimate their association with prostate cancer and obesity.
While no significant associations were detected between any of the tested SNPs and prostate cancer, the rs1501299 SNP in ADIPOQ was significantly associated with body mass (p=0.03).
Genetic variation in ADIPOQ and ADIPOR1 did not predict risk of prostate cancer in this study of African American men. However, the rs1501299 SNP in ADIPOQ was associated with obesity. Further investigation is warranted to determine if racial differences exist in the influence of the adiponectin pathway on prostate cancer risk.
adipokines; body mass index; genetic susceptibility; single nucleotide polymorphism; racial differences
Malignant giant cell tumor (GCT) of bone is a rare tumor with debilitating consequences. Patients with GCT of bone typically present with mechanical difficulty and pain as a result of bone destruction and are at an increased risk for fracture. Because of its unusual occurrence, little is known about the epidemiology of malignant GCT of bone. This report offers the first reliable population-based estimates of incidence, patient demographics, treatment course and survival for malignancy in GCT of bone in the United States. Using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program, we estimated the overall incidence and determinants of survival among patients diagnosed with malignant GCT of bone from 1975–2004. Cox proportional hazards regression was used to evaluate demographic and clinical determinants of survival among malignant GCT cases. Based on analyses of 117 malignant GCT cases, the estimated annual incidence in the United States was 1.6 per 10,000,000 persons per year. Incidence was highest among adults aged 20 to 44 years (2.4 per 10,000,000 per year) and most patients were diagnosed with localized (31.6%) or regional (29.9%) disease compared to distant disease (16.2%). Approximately 85% of patients survived at least 5 years, with survival poorest among older patients and those with evidence of distant metastases at time of diagnosis. The current study represents the largest systematic investigation examining the occurrence and distribution of malignancy in GCT of bone in the general U.S. population. We confirm its rare occurrence and suggest that age and stage at diagnosis are strongly associated with long-term survival.
giant cell tumor of bone; surveillance; epidemiology and end results; descriptive epidemiology; incidence; survival; osteosarcoma.
The mucosa of the small intestine encompasses about 90% of the luminal surface area of the digestive system, but only 2% of the total annual gastrointestinal cancer incidence in the United States.
The remarkable contrast in age-standardized cancer incidence between the small and large intestine has been reviewed with respect to the cell type patterns, demographic features, and molecular characteristics of neoplasms.
Particularly noteworthy is the predominance of adenocarcinoma in the colon, which exceeds 98% of the total incidence by cell type, in contrast to that of 30% to 40% in the small intestine, resulting in an age-standardized ratio of rates exceeding 50-fold. The prevalence of adenomas and carcinomas is most prominent in the duodenum and proximal jejunum. The positive correlation in global incidence rates of small and large intestinal neoplasms and the reciprocal increases in risk of second primary adenocarcinomas suggest that there are common environmental risk factors. The pathophysiology of Crohn inflammatory bowel disease and the elevated risk of adenocarcinoma demonstrate the significance of the impaired integrity of the mucosal barrier and of aberrant immune responses to luminal indigenous and potentially pathogenic microorganisms.
In advancing a putative mechanism for the contrasting mucosal susceptibilities of the small and large intestine, substantial differences are underscored in the diverse taxonomy, concentration and metabolic activity of anaerobic organisms, rate of intestinal transit, changing pH, and the enterohepatic recycling and metabolism of bile acids. Experimental and epidemiologic studies are cited that suggest that the changing microecology, particularly in the colon, is associated with enhanced metabolic activation of ingested and endogenously formed procarcinogenic substrates.
Cancer Epidemiology; Molecular Biology; Neuroendocrine Tumor; Adenocarcinoma; Non-Hodgkin Lymphoma; Gastrointestinal Stromal Tumor; Crohn Disease; Celiac Disease; Microbial Flora; Bile Acid Metabolism
Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer.
Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate (<50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources.
While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88).
Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.
Genetic epidemiology; Single nucleotide polymorphisms; Urothelial cancer; Arsenic methylation
Men who have a brother with prostate cancer have a two-fold increased risk of being diagnosed with prostate cancer. Strategies employed by these men to reduce prostate cancer risk are not well understood. Preliminary studies have shown that men with a family history of prostate cancer have a high rate of vitamin and supplement usage aimed at the prevention of prostate cancer.
We analyzed data from a cross-sectional study of men with familial and hereditary prostate cancer and their unaffected brothers. We interviewed 542 unaffected men who had at least one brother who had been diagnosed with prostate cancer regarding their use of vitamins and supplements, as well as the motivation for use.
The associations between subject characteristics and vitamin and supplement use were evaluated using an unconditional logistic regression modeling approach.
Overall, 59.2 and 36.5 percent of men reported ever using and currently using, respectively, one or more vitamins or supplements (including multivitamins). One-third of men took a vitamin or supplement that has been targeted for prostate health or cancer prevention, including green tea, magnesium, male hormones, saw palmetto, selenium, soy, vitamins A, C, E and zinc. Increasing age at time of survey was associated with vitamin/supplement use (OR=1.03; 95% CI=1.01–1.0). After adjusting for age at time of survey, being younger than an affected brother was associated with vitamin and supplement use (OR=1.51; 95% CI=1.01–2.25). 25% of men reported obtaining information from books or articles as the most common source of information.
Our findings indicate that men at an increased risk for prostate cancer report a high rate of vitamin and supplement use, including supplements targeted for prostate cancer prevention. Men with a family history of prostate cancer represent a target population for future chemopreventative agents.
Prostate Cancer Chemoprevention; Family History; Complementary and Alternative Medicine
Fractures are a recognized consequence of androgen deprivation therapy (ADT); however, less is known about the incidence of fracture in relation to the timing of ADT use or the impact of fracture on mortality in men with prostate cancer.
Using data from the Surveillance, Epidemiology, and End Results–Medicare linked database, we estimated adjusted hazard ratios (aHRs) using time-dependent Cox regression for fracture incidence related to the recency of exposure and dose among prostate cancer patients on gonadotropin-releasing hormone (GnRH) agonists, as well as mortality associated with fractures.
In our cohort of 80 844 patients, ADT was associated with an increased rate of fracture in both non-metastatic patients (aHR = 1.34; 95% confidence interval [CI] = 1.29–1.39) and metastatic patients (aHR = 1.51; 95%CI = 1.36–1.67). Fracture rates increased with increasing cumulative GnRH dose but decreased with increasing number of months since last use in each dose category. The mortality rate doubled for men experiencing a fracture after their diagnosis compared with that for men who did not experience a fracture (aHR = 2.05; 95%CI = 1.98–2.12).
ADT in elderly men with prostate cancer increased the incidence of fractures, and the effect appears to diminish with increasing time since the last dose of a GnRH agonist. Experiencing a fracture after the diagnosis of prostate cancer was associated with decreased survival.
epidemiology; prostate cancer; GnRH agonist; orchiectomy; SEER–Medicare; mortality; skeletal-related events
As an evolutionary response to prevent malaria infection, most Africans do not express the Duffy Antigen/Receptor for Chemokines (DARC) on their red blood cells. Results from experimental studies suggest that DARC expression inhibits prostate-tumor growth. We tested the hypothesis that men of African descent who lack DARC expression are at increased risk of prostate cancer. A case–control study involving 81 age-matched pairs was conducted in Jamaica. Participants were interviewed to collect data, and they donated blood for determination of DARC expression. Logistic regression was used to estimate associations with prostate cancer and aggressive disease. Little or no association was observed between erythrocyte DARC expression and prostate cancer or between DARC expression and aggressive disease. These associations changed little when adjusting for other potential confounders. Our results do not support an effect of erythrocyte DARC expression on the risk or progression of prostate cancer in men of African descent.
Prostate cancer; DARC; African descent; Epidemiology; Chemokine receptors; Erythrocytes
Metabolic syndrome refers to cluster of conditions serving as risk factors for cardiovascular disease. Metabolic syndrome is prevalent in the United States and the spectrum of specific features has been shown to differ by race and ethnicity. A number of recent reports link metabolic syndrome to prostate cancer, however most studies do not have racially diverse populations to explore differences in risk.
A case-control study was conducted to test the association between metabolic syndrome features and prostate cancer among 637 cases and 244 controls, with African Americans comprising 43% of the study population.
Metabolic syndrome, defined using a modified version of the ATP III criteria, was marginally associated with increased risk of prostate cancer in African Americans (OR=1.71; 95% CI=0.97, 3.01), but not Caucasians (OR=1.02; 95%CI=0.64, 1.62). After stratifying cases on stage at diagnosis, African American men with organ confined disease were more likely to have a history of metabolic syndrome compared to controls (OR=1.82; 95% CI=1.02, 3.23), but no association was observed among those with advanced stage disease (OR=0.93; 95%CI=0.31, 2.77). When evaluating specific features of metabolic syndrome, obesity was inversely related to prostate cancer among Caucasians (OR = 0.51, 95% CI=0.33, 0.80), but unrelated to risk among African Americans (OR=1.15; 95% CI=0.70, 1.89).
In this investigation, metabolic syndrome was associated with prostate cancer risk in African American men, but not Caucasians. The prevalence of this syndrome, coupled with the racial disparity and prostate cancer incidence and outcomes after diagnosis warrant further investigation.
insulin resistance; aggressive prostate cancer; African American; hypertension; diabetes; obesity
Prostate cancer linkage studies have been used to localize rare and presumably highly penetrant cancer susceptibility genes. Underlying genetic heterogeneity, as well as the high sporadic background of the disease, has resulted in many signals that are often not reproducible between research studies.
We conducted a SNP-based genome wide linkage scan on 131 Caucasian prostate cancer families participating in the University of Michigan Prostate Cancer Genetics Project (PCGP).
The strongest evidence for linkage was detected at 16q23 (LOD = 2.70 at rs1079635). Prostate cancer linkage to the same region of 16q23 has been observed by others and the region contains several strong candidate genes including the known prostate cancer tumor suppressor genes ATBF1 and WWOX. This linkage signal was not detected in our prior linkage study on 175 PCGP families, illustrating the genetic heterogeneity underlying prostate cancer susceptibility.
Further linkage studies in combination with tumor analyses from linked families are in progress to identify the putative hereditary prostate cancer gene at 16q23.
familial; gene; epidemiology; aggressive disease
Recent admixture mapping and linkage/association studies have implicated an ~1 Mb region on chromosome 8q24 in prostate cancer susceptibility. In a subsequent follow-up investigation, Haiman et al. (Nat Genet 2007;39:638-44) observed significant, independent associations between 7 markers within this region and sporadic prostate cancer risk in a multi-ethnic sample. To clarify the risk associated with hereditary prostate cancer, we tested for prostate cancer association with 6 of these 7 markers in a sample of 1,015 non-Hispanic white men with and without prostate cancer from 403 familial and early-onset prostate cancer families. Single nucleotide polymorphisms (SNPs) rs6983561 and rs6983267 showed the strongest evidence of prostate cancer association. Using a family-based association test, the minor (“C”) allele of rs6983561 and the major (“G”) allele of rs6983267 were preferentially transmitted to affected men (p < 0.05), with estimated odds ratios (ORs) of 2.26 (95% confidence interval of 1.06–4.83) and 1.30 (95% confidence interval of 0.99–1.71), respectively, for an additive model. Notably, rs6983561 was significantly associated with prostate cancer among men diagnosed at an early (<50 years) but not later age (p = 0.03 versus p = 0.21). Similarly, the association with rs6983267 was (not) statistically significant among men with(out) clinically aggressive disease (p = 0.007 versus p = 0.34). Our results confirm the association of prostate cancer with several of the SNPs on chromosome 8q24 initially reported by Haiman et al. In addition, our results suggest that the increased risk associated with these SNPs is approximately doubled in individuals predisposed to develop early onset or clinically aggressive disease.
prostate; cancer; genetics; chromosome 8; risk
Recent studies suggest obesity is associated with lower serum PSA, perhaps influencing recommendation for prostate biopsy, potentially explaining part of the observed poorer prognosis among obese men. African American men have the highest rates of prostate cancer and are more likely to die of the disease making early detection a priority in this group. We present findings from the Flint Men’s Health Study, a study in African American men, which are consistent with most studies suggesting that overweight men have PSA levels 0.15–0.30 ng/mL lower than those who are not overweight. We have coupled our results with a systematic review of publications in this area.
Obesity; Body Mass Index; Waist Circumference; Height; Prostate Cancer; Free PSA; African Americans