Betsy Higgins

The association of body mass index and prostate-specific antigen in a population-based study

Recent studies of men with prostate carcinoma suggest that obesity may be associated with more advanced‐stage disease and lower overall survival rates. One possible link between body mass index (BMI) and prostate carcinoma prognosis may be disease ascertainment. Prostate‐specific antigen (PSA) is widely used to screen for prostate carcinoma.

Obesity, adipokines, and prostate cancer in a prospective population-based study

Background: The purpose of this investigation was to examine the association of obesity and the adipokines leptin, adiponectin, and interleukin-6 (IL-6) with prostate cancer risk and aggressiveness. Methods: One hundred twenty-five incident prostate cancer cases and 125 age-matched controls were sampled from among participants in the original San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. The odds ratios (OR) of prostate cancer and high-grade disease (Gleason sum >7) associated with the WHO categories of body mass index (kg/m2) and with tertiles of serum concentrations of adiponectin, leptin, and IL-6 were estimated using multivariable conditional logistic regression models. Results: Body mass index was not associated with either incident prostate cancer [obese versus normal; OR, 0.75; 95% confidence interval (95% CI), 0.38-1.48; Ptrend = 0.27] or high-grade versus low-grade disease (OR, 1.17; 95% CI, 0.39-3.52; Ptrend = 0.62). Moreover, none of the three adipokines was statistically significant associated with prostate cancer risk or high-grade disease, respectively: leptin (highest versus lowest tertile; OR, 0.77; 95% CI, 0.28-1.37; Ptrend = 0.57; OR, 1.20; 95% CI, 0.48-3.01; Ptrend = 0.85); adiponectin (OR, 0.87; 95% CI, 0.46-1.65; Ptrend = 0.24; OR, 1.93; 95% CI, 0.74-5.10; Ptrend = 0.85); IL-6 (OR, 0.84; 95% CI, 0.46-1.53; Ptrend = 0.98; OR, 0.84; 95% CI, 0.30-2.33; Ptrend = 0.17). Conclusions: Findings from this nested case-control study of men routinely screened for prostate cancer and who had a high prevalence of overweight and obesity do not provide evidence to support that prediagnostic obesity or factors elaborated by fat cells strongly influence prostate cancer risk or aggressiveness. However, due to the small sample population, a small or modest effect of obesity and adipokines on these outcomes cannot be excluded. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1331–5)

Androgen Receptor Length Polymorphism Associated with Prostate Cancer Risk in Hispanic Men

PURPOSE The transcriptional activation domain of the androgen receptor gene includes a CAG repeat length polymorphism. A smaller number of repeats is reported to increase the risk of prostate cancer. We investigated the association of CAG repeat length and the risk of prostate cancer in a case-control study of Hispanic men. MATERIALS AND METHODS To estimate the magnitude of the association of repeat length with prostate cancer risk, samples from 82 white patients of Hispanic origin (Hispanic) with prostate cancer and 145 Hispanic controls were genotyped. To determine the allelic distribution of repeats by race/ethnicity we genotyped 132 black men, 163 white men of nonHispanic origin (white) and 175 Hispanic men with no family history of prostate cancer, and performed pairwise comparison. RESULTS In the case-control study of Hispanic men with a repeat length of 18 or less versus greater than 18 we found an approximately 3-fold increased risk of prostate cancer (OR 2.7, 95% CI 1.21 to 6.01, t test p = 0.013, age adjusted OR 3.03, 95% CI 1.27 to 7.26). The distribution of alleles differed significantly by race/ethnicity. The mean prevalence of short CAG repeat alleles plus or minus SD was higher in black than in white men (19.8 +/- 3.2 versus 21.8 +/- 2.7, t test p <0.0001) and lower in Hispanic men than in other white men (22.7 +/- 3.3, t test p = 0.014). CONCLUSIONS To our knowledge, our study represents the first case-control study of the androgen receptor gene in a Hispanic population and provides evidence of the increased prostate cancer risk associated with short CAG repeats. Our results suggest that short CAG repeats are associated with an increased prostate cancer risk in Hispanic men.

Association Between an Eestrogen Receptor Alpha Gene Polymorphism and the Risk of Prostate Cancer in Black Men

PURPOSE Studies suggest that SNPs within ESR1 may be associated with an increased risk of prostate cancer. We evaluated the association of the XbaI and PvuII ESR1 SNPs and prostate cancer risk in 3 different racial/ethnic populations. MATERIALS AND METHODS A total of 1,603 volunteers from the SABOR study (285 black, 876 white and 442 Hispanic men) were genotyped to assess allelic frequencies of the ESR1 SNPs. Case-control analysis was performed on 598 prostate cancer cases and 1,098 controls (260 black men, 1,013 non-Hispanic white men and 423 Hispanic white men) to assess the association between these polymorphisms and prostate cancer risk. RESULTS Allelic frequency was significantly different across ethnic/racial groups for both SNPs. Logistic regression analysis adjusted for age and stratified by race and ethnicity demonstrated an association between the AG genotype or presence of the G allele (GG or AG genotype) in the XbaI SNP and prostate cancer risk within black men (OR 2.25, 95% CI 1.07-4.70, p = 0.031; OR 2.14, 95% CI 1.05-4.35, p = 0.035, respectively). No association was observed among Hispanic and non-Hispanic white men for this SNP. Furthermore, there was no association between the PvuII SNP and prostate cancer risk across all groups. CONCLUSIONS Our study demonstrates an association between the AG genotype, as well as presence of the G allele within the XbaI ESR1 SNP and prostate cancer risk among black men.

Assessment of 54 biomarkers for biopsy-detectable prostate cancer.

Objective: We analyzed the association of 54 biomarkers from seven classes including adipokines, immune response metalloproteinases, adhesion molecules, and growth factors with prostate cancer risk adjusting for the Prostate Cancer Prevention Trial (PCPT) risk score. Methods: A total of 123 incident prostate cancer cases and 127 age-matched controls were selected from subjects in the San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. Prediagnostic serum concentrations were measured in the sample collected at baseline using LabMAP technology. The odds ratios (OR) of prostate cancer risk associated with serum concentrations of 54 markers were estimated using univariate conditional logistic regression before and after adjustment for the PCPT risk score. Two-way hierarchical unsupervised clustering techniques were used to evaluate whether the 54-marker panel distinguished cases from controls. Results: Vascular endothelial growth factor, resistin, interleukin 1Ra (IL-1Ra), granulocyte colony-stimulating factor, matrix metalloproteinase-3, plasminogen activator inhibitor, and kallikrein-8 were statistically significantly (P < 0.05) underexpressed in prostate cancer cases, and α-fetoprotein was statistically significantly overexpressed in prostate cancer cases, but all had area underneath the receiver-operating characteristic curve <60%; none were statistically significant adjusting for multiple comparisons (P < 0.0008) or after adjustment for the PCPT risk score. Statistical clustering of patients by the marker panel did not distinguish a separate group of cases from controls. Conclusions: This age-matched case-control study did not support findings of increased diagnostic potential from a 54-marker panel when compared with the conventional risk factors incorporated in the PCPT risk calculator. Future discovery of new biomarkers should always be tested and compared against conventional risk factors before applying them in clinical practice. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1966–72)

Interobserver variability in prostate cancer specific survival

We evaluated the reliability of disease-specific survival (DSS) as an outcome measure in patients with carcinoma of the prostate (CaP). The records of 50 patients had a diagnosis of CaP and had expired were selected from the hospital tumor registry. Records were reviewed by six individuals and each individual was asked to specify cause of death as due to CaP or some other cause. DSS curves were generated based on the determinations of each reviewer. Although the DSS curves were generally parallel, a high degree of variability was seen at various intervals, leading us to conclude that DSS is dependent upon the individual reviewer. Published by Elsevier Science Inc.