Smoking and prostate cancer in a multi-ethnic cohort.

BACKGROUND: Prostate cancer (PCa) and smoking-related morbidity disproportionately burdens African American (AA) men. Smoking is associated with high-grade PCa and incidence, but few studies have focused on AA men. This study aims to determine the effect of tobacco-use on odds of PCa and of high-grade PCa in a population of predominantly AA men. METHODS: This is a cross-sectional study evaluating smoking and PCa status in men with incident PCa and screened healthy controls. Altogether, 1,085 men (527 cases and 558 controls), age ≥ 40 years were enrolled through outpatient urology clinics in two US cities from 2001 to 2012. Validated questionnaires were used to gather clinical and socioeconomic data. RESULTS: The cases and controls were predominantly AA (79.9% and 71.3%, respectively, P = 0.01). AA men smoked more frequently (53.4% vs. 47.9%, P < 0.001) and quit less frequently than European American (EA) men (31.5% vs. 40.4%, P = 0.01). AA heavy smokers had increased odds of PCa diagnosis (OR 2.57, 95% CI 1.09, 6.10) and high-grade cancer (OR 1.89, 95% CI 1.03, 3.48) relative to never smokers and light smokers. Among AAs, heavy smokers had lower odds of NCCN low PCa recurrence risk stratification. AA former smokers had a trend for increased odds of high-grade cancer compared to never smokers. The associations between smokings, cancer diagnosis and cancer grade did not reach statistical significance in EA men. CONCLUSION: We found ethnic differences in smoking behavior. Heavy smoking is associated with increased odds of PCa and of higher Gleason grade in AA men.

Racial variation in vitamin D cord blood concentration in white and black male neonates.

AIM: The aim of this study is to evaluate racial variation in umbilical cord blood concentration of vitamin D and to explore its correlation with markers of the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and black male neonates. METHODS: In 2004-2005, venous umbilical cord blood samples were collected from 75 black and 38 white male neonates, along with maternal and birth characteristics from two hospitals in Maryland, United States. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured by radioimmunoassay and testosterone, estradiol, and sex hormone-binding globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed. RESULTS: Mean 25(OH)D levels were lower in black than in white neonates (11.44; 95 % CI 10.10-12.95 ng/mL vs. 18.24; 95 % CI 15.32-21.72 ng/mL; p < 0.0001). Black neonates were at higher risk of suboptimal vitamin D levels [25(OH)D < 20 ng/mL] than whites (84 vs. 63 %). 25(OH)D concentrations varied by season in whites but not in blacks and were significantly inversely correlated with mother's parity (number of live births) in blacks but not in whites. Mean concentration of 1,25(OH)(2)D did not differ by race. 25(OH)D and 1,25(OH)(2)D did not correlate with IGFs, sex steroid hormones, and SHBG. CONCLUSIONS: Suboptimal vitamin D levels were prevalent especially in blacks and influenced by mother's parity and by season. The observed vitamin D differences between black and white neonates warrant further evaluation of the etiology of the disparity in chronic diseases in adulthood.

Racial variation in umbilical cord blood sex steroid hormones and the insulin-like growth factor axis in African-American and white female neonates.

PURPOSE: To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis between female African-American and white neonates. METHODS: Maternal and birth characteristics and venous umbilical cord blood samples were collected from 77 African-American and 41 white full-term uncomplicated births at two urban hospitals in 2004 and 2005. Cord blood was measured for testosterone, dehydroespiandrosterone-sulfate, estradiol, and sex steroid hormone-binding globulin (SHBG) by immunoassay. IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP-3) were measured by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed for the hormones. RESULTS: African-American neonates weighed less at birth (3,228 g vs. 3,424 g, p < 0.004) than whites. Birth weight was positively correlated with IGF-1, IGFBP-3, and the molar ratio of IGF-1 to IGFBP-3, but inversely correlated with the molar ratio of IGF-2 to IGFBP-3. Adjusted models showed higher testosterone (1.82 ng/ml vs. 1.47 ng/ml, p = 0.006) and the molar ratio of testosterone to SHBG (0.42 vs. 0.30, p = 0.03) in African-American compared to white female neonates. IGF-1, IGF-2, and IGFBP-3 were lower in African-American compared to white female neonates, but only the difference for IGF-2 remained significant (496.5 ng/ml vs. 539.2 ng/ml, p = 0.04). CONCLUSION: We provide evidence of racial variation in cord blood testosterone and testosterone to SHBG in African-American compared to white female neonates, and higher IGF-2 in white compared to African-American female neonates. Findings suggest plausible explanations for a prenatal influence on subsequent breast cancer risk and mortality. Further work is needed to confirm these observations.

Racial variation in sex steroid hormones and the insulin-like growth factor axis in umbilical cord blood of male neonates.

BACKGROUND: To address whether umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis differ between African-American and White male neonates. METHODS: In 2004 and 2005, venous cord blood samples were collected from 75 African-American and 38 White male full-term uncomplicated births along with birth weight, placental weight, mother's age and parity, and time of birth. Testosterone, androstanediol glucuronide, estradiol, and sex hormone binding globulin (SHBG) were measured by immunoassay, and IGF-I, IGF-2, and IGF binding protein (BP)-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed. RESULTS: Androstanediol glucuronide, estradiol, and SHBG concentrations did not differ by race; however, the molar ratio of testosterone to SHBG was higher in African-American than White male babies after adjustment (P = 0.01). Both before and after adjustment, Whites had higher concentrations of IGF-I (adjusted; White, African-American, 93.1, 71.9 ng/mL), IGF-2 (537.3-474.8 ng/mL), and IGFBP-3 (1,673-1,482 ng/mL) than African-Americans (P < 0.05), although the molar ratio of IGF-I plus IGF-2 to IGFBP-3 did not differ by race. CONCLUSION: The higher cord blood testosterone to SHBG ratio in African-American compared with White male babies after taking into account maternal and birth factors is compatible with the hypothesis that differences in androgen levels in utero contribute to their higher prostate cancer risk, although we would have expected crude differences as well. Lower cord blood IGF-I and IGF-2 levels in African-American compared with White male babies are not consistent with the hypothesis that differences in growth factor levels contribute to their higher prostate cancer risk.

Sequence variation within the 5' regulatory regions of the vitamin D binding protein and receptor genes and prostate cancer risk.

BACKGROUND: The vitamin D receptor (VDR) and binding protein (DBP) mediate the cellular transport, activity, and anti-tumor action of 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D3]. The purpose of this investigation is to determine whether novel single nucleotide polymorphisms (SNPs) within the transcriptional regulatory regions of the VDR and DBP are associated with prostate cancer risk. METHODS: Novel SNPs were identified in the VDR and DBP transcription regulatory gene regions and genotyped in a case-control study using male subjects with (n=258) or without (n=434) prostate cancer. RESULTS: African-American men who possessed at least one variant VDR-5132 C allele had a increased risk of prostate cancer (OR=1.83; 95% CI: 1.02, 3.31). Further study revealed that the VDR-5132 T/C SNP eliminates a GATA-1 transcription factor-binding site. CONCLUSION: The VDR-5132 T/C SNP, resulting in potential elimination of the GATA-1 transcription factor-binding site, may increase prostate cancer susceptibility in African-Americans. Confirmation of these findings is needed in larger observational studies.

Prevalence of elevated serum prostate-specific antigen in rural Nigeria.

BACKGROUND: Recent hospital and cancer registry data show increasing prostate cancer incidence in Nigeria, which was previously regarded as a low incidence region. This study investigates the prevalence of prostate cancer risk in a previously unscreened cohort of rural Nigerians. METHODS: Rural Nigerian men, 40 years and older, were screened by serum prostate-specific antigen (PSA) and digital rectal examination (DRE) and those with PSA >/= 4 ng/mL and/or abnormal DRE were referred for prostate biopsy. RESULTS: Of 200 consecutive men invited, 151 (75.5%) presented for screening, the mean age was 56.45 + 15.1 and 95 (61.6%) were >/= 50 years of age. Of the 140 who consented to a blood test, PSA correlated with age (r = 0.3, P < 0.01), 14 (10.0%) had abnormal PSA >/= 4 ng/mL, increasing from 3 (3.6%) in men < 60 years to 4 (50%) in men >/= 80 years. The rate was 13 (15.7%) for men >/= 50 years and there was no evidence of increased incidence of prostatitis in the community. Mean (median) PSA in ng/mL increased from 1.17 (0.60) in the youngest to 13.75 (4.45) in the oldest cohort. Of those who accepted DRE, 38 (29.0%) had an enlarged prostate, including two who had nodular prostate, one-third with symptoms, increasing from 4 (5.4%) in those < 50 years to 6 (75.0%) in men >/= 80 years. The proportion of men with PSA >/= 4 ng/mL among those with enlarged vs normal prostate is 27.0 to 3.4%, P < 0.001, and the pattern was similar for men >/= 60 years and those < 60 years of age. The 40 (32.0%) men referred for prostate biopsy defaulted mainly because they did not fully understand the need for further investigation because they were symptom free or afraid of the possible side-effects of the procedure or diagnosis of cancer. CONCLUSION: The proportion of men with PSA >/= 4 ng/mL is comparable to that of previously unscreened populations with high incidence of prostate cancer such as African-American men. A larger study is required to confirm these findings and intensify efforts to determine the prostate cancer detection rate by biopsy in this population. A prostate cancer awareness and education campaign will be useful in this community.