Basic Science.
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Cholestenone 5 alpha-Reductase↗
Biomedical subjects
E A Platz
Publications and source records attributed to E A Platz.
Selenium, zinc, and prostate cancer.
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Cell Transformation, Neoplastic↗
Racial variation in prostate cancer incidence and in hormonal system markers among male health professionals.
BACKGROUND: Racial variation in prostate cancer incidence in the United States is pronounced, with African-American men having the highest rates. Whether differences in the distribution of known or suspected risk factors among racial groups explain this variation is unknown. METHODS: We evaluated prospectively the relation between prostate cancer and race among 45 410 U.S. male health professionals aged 40--75 years in 1986. We used multivariable, pooled logistic regression to adjust the rate ratio (RR) for potential dietary and lifestyle risk factors. We also measured circulating levels of steroid hormones, sex hormone-binding globulin, and vitamin D metabolites and length of the androgen receptor gene CAG repeat in a sample of African-American (n = 43), Asian (n = 52), and white (n = 55) participants and assessed variation by race in these possible prostate epithelial cell growth mediators by use of analysis of variance. Statistical tests were two-sided. RESULTS: The age-adjusted RR for prostate cancer was 1.73 (95% confidence interval [CI] = 1.23--2.45) for African-American men compared with white men. After multivariate adjustment, the RR increased to 1.81 (95% CI = 1.27--2.58). The rate of prostate cancer did not differ between Asians and whites. Steroid hormone and 1,25-dihydroxyvitamin D levels did not vary appreciably by race. However, the mean number of androgen receptor gene CAG repeats was lower among African-Americans (mean +/- standard deviation = 20.1 +/- 3.5) than among whites (22.1 +/- 3.1; P =.007) and Asians (22.1 +/- 3.9; P =.009). CONCLUSIONS: Our results confirm the elevated incidence of prostate cancer among African Americans and show that it is not explained by differences in the distribution of possible dietary and lifestyle risk factors in this cohort. Racial variation in length of the androgen receptor gene CAG repeat may explain a small part of the excess risk of prostate cancer among African-American men in this cohort.
Adult↗
Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and the risk of colorectal adenoma and cancer in the Nurses' Health Study.
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Adenoma↗
Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men.
OBJECTIVE: Diet and lifestyle likely play major roles in colon cancer incidence; however, the proportion of colon cancer risk that might be preventable is unknown. Thus, we estimated the proportion of colon cancer risk among men in the prospective Health Professionals Follow-up Study that might be attributable to a constellation of modifiable risk factors, and thus might be preventable. METHODS: We included 47,927 men aged 40-75 years in 1986, among whom we confirmed 411 colon cancer cases from 1986 to 1996. Risk factors considered were obesity, physical inactivity, alcohol consumption, early adulthood cigarette smoking, red meat consumption, and low intake of folic acid from supplements. We calculated a risk score that was the sum across the six risk factors of the values of 1 (better exposure) to 5 (worse exposure) corresponding to the exposure category. We entered the risk score into a logistic regression model and estimated the population attributable risk percent (PAR%) using the method of Bruzzi et al. RESULTS: After adjusting for age and family history of colorectal cancer and comparing the risk score for the combined six modifiable colon cancer risk factors at or above the approximate 20th, 10th, or 5th percentiles vs. below, the PAR% increased from 39% (95% confidence interval (CI) = 23-58%), to 48% (95% CI = 25-71%), to 55% (95% CI = 27-80%), respectively. Using a second method in which we used cut-points consistent with general-good health behaviors for each risk factor, comparing men with at least one risk factor to men without any risk factors (3.1% of the men), the PAR% was 71% (95% CI = 33-92%). CONCLUSION: The findings from this analysis suggest that, if all the members of this cohort of middle-aged US men had a modifiable exposure distribution comparable to the men with low risk scores, a large proportion of colon cancer risk might be avoidable. Additional study is required to determine whether making changes in these six risk factors now would reduce the risk of colorectal neoplasia, or whether the proportion of colon neoplasia that might be avoidable would be similar in populations with different characteristics.
Adenoma↗
Bowel movement, use of laxatives and risk of colorectal adenomatous polyps among women (United States).
BACKGROUND: Infrequent bowel movements and use of laxatives have been hypothesized to increase risk of colorectal neoplasia. However, the few existing epidemiologic studies in humans have been inconclusive. PURPOSE: To investigate prospectively the associations of bowel movement frequency and laxative use with the occurrence of adenomatous colorectal polyps in women. METHODS: A total of 17,400 women 36-61 years of age, without previous diagnosis of cancer or polyps, responded to a mailed questionnaire in 1982 that assessed bowel movement frequency and use of laxatives and had an endoscopy between 1984 and 1996. Between 1984 and 1996, 906 cases of adenomatous polyps (496 classified as small (< 1 cm), 358 classified as large (> or = 1 cm) and 52 unclassified) were documented. Relative risks (RRs) of adenomas and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: After controlling for adenoma risk factors, the multivariate RRs associated with having bowel movements every third day or less compared to once daily were 0.9 (95% CI: 0.7-1.2) for total colorectal adenomas, 1.0 (95% CI: 0.7-1.5) for large adenomas and 1.0 (95% CI: 0.7-1.3) for adenomas of the colon only. The multivariate RRs associated with weekly to daily laxative use compared to never use were 0.9 (95% CI: 0.7-1.1) for total colorectal adenomatous polyps, 1.0 (95% CI: 0.7-1.5) for large adenomas and 0.8 (95% CI: 0.6-1.2) for colon adenomatous polyps only. CONCLUSION: These findings do not support an association between infrequent bowel movement or laxative use and risk of colorectal adenomas.
Adenomatous Polyps↗
Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors.
PURPOSE: Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an alpha-emitter. Epidemiologic studies have observed markedly elevated risks of death from hepatic and hematologic cancers and extensive chromosomal damage among these patients. Few investigations have correlated multiple measures of genetic damage to determine whether these have independent induction kinetics. The distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long-term thorotrast survivors (mean exposure time=47.4 years) and five individuals who received a nonradioactive contrast medium during the same era. MATERIALS AND METHODS: Peripheral blood lymphocytes were harvested from whole blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprt MF. Symmetrical aberrations were not evaluated. Differences in frequencies and correlations between endpoints were assessed using nonparametric methods. RESULTS: Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 cells [median, mean +/- sd]: 11, 18.3+/-23.1 vs 2, 2.4+/-1.1, p =0.04). There was no difference between the groups on hprt MF (12.6, 15.9+/-13.5 vs 16.6, 14.0+/-8.8[ x 10(-6)]; p= 1.0). Among the exposed, hprt MF was moderately correlated with the frequency of asymmetrical chromosomal aberrations, although the association was not statistically significant. CONCLUSION: Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.
Adult↗
Race, ethnicity and benign prostatic hyperplasia in the health professionals follow-up study.
PURPOSE: We examined whether the prevalence of benign prostatic hyperplasia (BPH) varies by racial or ethnic origin in a large cohort of American male health professionals. MATERIALS AND METHODS: Included in our study were 1,508 men who underwent surgery for BPH between 1986 and 1994, and 1,837 with high moderate to severe lower urinary tract symptoms assessed by the American Urological Association symptom index in 1992 or 1994. "Noncases" comprised 23,246 asymptomatic participants. Self-reported major ancestry was black in 201 men, Asian in 413, other origin in 604 and white in 25,373. White heritage was further classified as southern European in 6,408 men, Scandinavian in 2,951 and other white in 16,014. The relative risk of BPH and 95% confidence intervals (CI) adjusted for age, body mass index, alcohol consumption, smoking and physical activity were calculated by logistic regression. RESULTS: Black men were not at increased risk for BPH (relative risk 0.85, 95% CI 0.55 to 1.31) compared with white men. Asian men were less likely to have undergone BPH surgery (relative risk 0.41, 95% CI 0.21 to 0.82), although the relative risk for symptoms was similar to that of white men. White men whose major ancestry was southern European were at modestly higher risk for BPH surgery (relative risk 1.28, 95% CI 1.12 to 1.46) and symptoms (relative risk 1.34, 95% CI 1.20 to 1.50), whereas men of Scandinavian heritage were at slightly decreased risk for symptoms than those of other white heritages. CONCLUSIONS: Racial and ethnic variation is evident in the incidence of BPH surgery and symptom severity. Whether this observed variation reflects underlying biological phenomena rather than differences in symptom tolerance requires further exploration.
Adult↗
A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women.
Insulin-like growth factor-1 (IGF-1) is an important mitogen, and IGF binding protein-3 (IGFBP-3) has opposing effects. Acromegalics, who have abnormally elevated levels of IGF-1, are at increased risk of colorectal tumors. Recent studies have found that IGF-1 levels correlate with risk of prostate cancer and colorectal cancer in men, premenopausal breast cancer in women, and lung cancer in men and women. We examined whether prediagnostic plasma levels of IGF-1 and IGFBP-3 influence risk of colorectal cancer and adenoma in women. From 1989 to 1990, a total of 32,826 women from the Nurses' Health Study provided blood specimens that were archived in liquid nitrogen. During 6 years of follow-up from 1989 to 1994, we documented 79 new cases of colorectal cancer, 90 cases of intermediate/late-stage adenoma (> or =1 cm or tubulovillous/villous histology), and 107 cases of early-stage adenoma (<1 cm and tubular histology). After matching controls (2:1 for cancers and 1:1 for adenomas) to cases by age, month of blood draw, fasting status, and indication for endoscopy (for adenoma controls), plasma IGF-1 and IGFBP-3 levels were measured. Controlling for IGFBP-3 level, relative to women in the low tertile of IGF-1, those in the high tertile were at elevated risk of intermediate/late-stage colorectal neoplasia adenoma [multivariate relative risk (RR), 2.78; 95% confidence interval (CI), 0.76-9.76] and cancer (RR, 2.18; 95% CI, 0.94-5.08). Controlling for IGF-1 level, relative to women in the low tertile of IGFBP-3, women in the high tertile of IGFBP-3 were at lower risk of intermediate/late-stage colorectal adenoma (RR, 0.28; 95% CI, 0.09-0.85) and cancer (RR, 0.28; 95% CI, 0.10-0.83). Neither IGF-1 nor IGFBP-3 had any appreciable relation with early-stage adenoma. These analyses indicate that high levels of circulating IGF-1 and particularly low levels of IGFBP-3 are associated independently with an elevated risk of large or tubulovillous/villous colorectal adenoma and cancer.
Adenoma↗
Vertex balding, plasma insulin-like growth factor 1, and insulin-like growth factor binding protein 3.
BACKGROUND: A recent report suggested that men with vertex balding have higher levels of plasma insulin-like growth factor 1 (IGF-1). The association of its major carrier protein, insulin-like growth factor binding protein 3 (IGFBP-3), with male pattern hair loss has not been examined. OBJECTIVE: We evaluated the relations of plasma concentrations of IGF-1 and IGFBP-3 with vertex balding in middle-aged and elderly men. METHODS: Participants were 431 male members of the Health Professionals Follow-up Study who responded to a question in 1992 on their hair pattern at 45 years of age and who were 47 to 81 years old when they provided a blood specimen in 1993-1994. Odds ratios (ORs) of vertex balding associated with IGF-1 and IGFBP-3 were estimated from logistic regression models mutually adjusting for each other and controlling for age at blood draw. RESULTS: Of the 431 men, 128 had vertex balding at age 45. Compared with men who were not balding, for a 1 standard deviation increase in plasma IGF-1 level (72.4 ng/mL), the OR for vertex balding was 1. 31 (95% CI, 0.95-1.81). For a 1 standard deviation increase in plasma IGFBP-3 (957 ng/mL), the OR for vertex balding was 0.62 (95% CI, 0.44-0.88). CONCLUSION: Older men with vertex balding have lower circulating levels of IGFBP-3 and higher levels of IGF-1 when controlling for IGFBP-3 level.
Aged↗
Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and adenomatous polyps of the distal colorectum.
1,25-dihydroxyvitamin D [1,25(OH)2D] inhibits proliferation and promotes differentiation of human colon cancer cell lines. Epidemiological findings, although not entirely consistent, suggest an inverse relationship between vitamin D intake and colorectal cancer and adenoma, colorectal cancer precursor lesions. We evaluated the relationship of plasma 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] with distal colorectal adenoma among 326 matched case and control pairs (nested in the prospective Nurses' Health Study), who provided blood in 1989-1990 and who underwent endoscopy in 1989-1996. Plasma vitamin D metabolite concentrations were determined blindly by RIA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple conditional logistic regression models. Mean plasma 1,25(OH)2D and 25(OH)D levels did not significantly differ (P = 0.3 and 0.7, respectively) between cases (31.6 +/- 8.4 pg/ml and 26.4 +/- 10.6 ng/ml, respectively) and controls (32.2 +/- 8.6 pg/ml and 26.8 +/-10.2 ng/ml, respectively). However, women whose plasma 1,25(OH)2D concentration was below 26.0 pg/ml (a level typically considered to be below normal) were at increased risk of distal colorectal adenoma (OR, 1.58; 95% CI, 1.03-2.40). Compared with the lowest 1,25(OH)2D quartile, women in the second (OR, 0.64; 95% CI, 0.41-1.02), third (OR, 0.80; 95% CI, 0.50-1.30), or upper (OR, 0.71; 95% CI, 0.43-1.15) quartiles were at a statistically nonsignificant lower risk of adenoma. The relationship was stronger for large/villous adenoma and among those with consistent vitamin D intake over the 10 years prior to blood draw. Compared with women in the lowest quartile, for plasma 25(OH)D, women in the second (OR, 0.64; 95% CI, 0.41-1.00) and third (OR, 0.58; 95% CI, 0.36-0.95) quartiles were at a statistically significantly lower risk of distal colorectal adenoma, but there was no difference in risk in the top quartile (OR, 1.04; 95% CI, 0.66-1.66). We conclude that women who have low levels of circulating 1,25(OH)2D may be at higher risk of distal colorectal adenomas, but additional study is warranted.
Adenoma↗
No association between the I105V polymorphism of the glutathione S-transferase P1 gene (GSTP1) and prostate cancer risk: a prospective study.
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Case-Control Studies↗
The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer.
5alpha-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5alpha-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5alpha-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% confidence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Alcohol consumption, cigarette smoking, and risk of benign prostatic hyperplasia.
Alcohol consumption and cigarette smoking were evaluated in relation to development of benign prostatic hyperplasia (BPH) among 29,386 members of the Health Professionals Follow-up Study. Men who were 40-75 years old in 1986 and free of prior BPH surgery, diagnosed cancer at baseline, and prostate cancer at baseline and during follow-up were followed for incidence of BPH surgery from 1986 to 1994. Cases were men who reported BPH surgery between 1986 and 1994 (n = 1,813) or who scored > or = 15 points of 35 on seven lower urinary tract symptom questions modified from the American Urological Association symptom index in 1992 and 1994 (n = 1,786); noncases were men who scored < or = 7 points (n = 20,840). After controlling for age, race/ethnicity, body mass index, physical activity, and mutually for alcohol intake and smoking, moderate alcohol consumption was inversely related with total BPH (30.1-50 g/day vs. 0: odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.51-0.70; p trend < 0.0001), although the relation was attenuated at high intake (> or = 50.1 g/day vs. 0: OR = 0.72, 95% CI 0.57-0.90). Current cigarette smoking was positively related to total BPH only among those who smoked 35 or more cigarettes/day (compared with never smokers: OR = 1.45, 95% CI 1.07-1.97). These findings suggest that moderate alcohol consumption and avoidance of smoking may benefit BPH.
Adult↗
The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia.
OBJECTIVES: Shorter CAG repeat lengths in exon 1 of the androgen receptor (AR) gene are associated with a stronger transcriptional activity of the AR and with a higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that men with shorter AR gene CAG repeat lengths have an increased risk of developing BPH. METHODS: Using data from the Health Professionals Follow-up Study (HPFS), we evaluated the relationship between AR gene CAG repeat length and prevalent BPH, as defined by BPH surgery, by enlarged prostate gland detected by digital rectal examination, and by urinary symptoms as determined by the American Urological Association Symptom Index. RESULTS: The odds ratio for BPH surgery or enlarged prostate gland was 1.92 (95% confidence interval [CI] 1.22 to 3.03; P [trend] = 0.0002), comparing AR gene CAG repeat length of 1 9 or less to 25 or more. Results were similar for the end points of BPH surgery (P [trend] = 0.002) and for enlarged prostate gland (P [trend] = 0.001). For a six-repeat decrease in CAG repeat length, the odds ratio for having moderate or severe urinary obstructive symptoms from an enlarged prostate gland was 3.62 (95% CI 1.51 to 8.67; P = 0.004). CONCLUSIONS: Variability in the AR gene CAG repeat influences the development of symptomatic BPH, particularly in predicting obstructive urinary symptoms. Our findings support further study to establish the appropriate clinical relevance.
Adult↗
Glycosylated hemoglobin and risk of colorectal cancer and adenoma (United States).
OBJECTIVES: The consistently observed epidemiologic associations of obesity and physical activity with colorectal cancer and precursor adenoma risk suggest that insulin and glucose control may be contributory. We evaluated the association of glycosylated hemoglobin (HbA1c), a clinical indicator of average glycemia over the previous 2 months, and possibly, indirectly, a marker of average blood insulin level, with colorectal carcinogenesis. METHODS: Among women in the Nurses' Health Study, who provided blood in 1989-90 and were diagnosed subsequently in 1989-94, we included 79 colorectal cancer cases and 156 matched controls, and 201 distal colorectal adenoma cases and 201 matched controls. HbA1c concentrations in red blood cells were determined blindly by turbidometric immunoinhibition. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression models. RESULTS: HbA1c level did not significantly differ between colorectal cancer cases (median 5.5%) and controls (5.5%, p = 0.5), although a small difference between adenoma cases (5.6%) and controls (5.5%, p = 0.06) was noted. Compared to the lowest tertile of HbA1c (median 5.2%), women in the middle (median 5.5%, OR = 1.2, CI = 0.6-2.5) and upper (5.8%, OR = 1.2, CI = 0.6-2.7) tertiles were not at an increased risk for colorectal cancer. A modestly elevated risk of distal colorectal adenoma in the upper (median 5.8%, OR = 1.4, CI = 0.9-2.3) versus lower (median 5.3%) tertile could not be excluded. These associations were not appreciably altered after adjusting for known and suspected colorectal cancer risk factors. CONCLUSION: Over the range of levels observed in this relatively small sample of middle-aged women, prediagnostic HbA1c does not clearly predict colorectal cancer and adenoma risk.
Adenoma↗
Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men.
African-American men have the highest and Asian-American men have the lowest prostate cancer incidence rates in the United States; internationally, rates for the Asian continent are among the lowest. Higher insulin-like growth factor (IGF)-1, which participates in the control of cellular growth and differentiation and is modulated by IGF-binding protein-3 (IGFBP-3), was associated with an increased prostate cancer risk in three recent studies. We, therefore, investigated whether plasma levels of IGF-1 and IGFBP-3 vary by race in United States men selected from among members of the Health Professionals Follow-up Study who were 47-78 years old in 1993-1995 when they provided blood (n = 18,000). All of the men who described their major ancestry as African American (n = 63) and a random sample of 75 Asians and 75 Caucasians were invited to provide a second blood sample in 1997, of whom 42, 52, and 55, respectively, did so. IGF-1 and IGFBP-3 concentrations were determined by ELISA. We used nonparametric methods to assess racial variation in age-adjusted levels. Caucasians had the highest median IGF-1 level (224 ng/ml), followed by Asians (208 ng/ml) and African Americans (205 ng/ml). Median IGFBP-3 concentration was similar between Caucasians and Asians but was more than 13% lower in African Americans. Median molar IGF-1:IGFBP-3 ratio was greatest in Caucasians and lowest in Asians. The lower IGF-1 blood levels relative to IGFBP-3 levels among Asian men are consistent with their lower prostate cancer incidence. Although differences in circulating IGF-1 do not seem to account for the greater prostate cancer risk among African-American men, their absolute lower levels of IGFBP-3 may be contributory.
Age Distribution↗
Physical activity and benign prostatic hyperplasia.
BACKGROUND: Benign prostatic hyperplasia (BPH) leading to prostatic enlargement and lower urinary tract symptoms is highly prevalent among older men. Sympathetic nervous system activity, which is decreased by physical activity, is associated with increased prostatic smooth-muscle tone and prostatic symptoms. Therefore, we assessed whether physical activity leads to fewer lower urinary tract symptoms in the Health Professionals Follow-up Study. METHODS: We observed men who were aged 40 to 75 years at baseline in 1986 for subsequent incidence of surgery for BPH. The men were free of diagnosed cancer, including prostate cancer at baseline and during follow-up, had not had a radical prostatectomy, and provided data on physical activity. Cases were men who under-went BPH surgery between 1986 and 1994 (n = 1890) or, among those who did not have surgery, who scored 15 or more points of 35 (n = 1853) on 7 questions about lower urinary tract symptoms modified from the American Urological Association Symptom Index. Noncases were men who scored 7 points or less (n = 21745). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from multiple logistic regression models. RESULTS: After controlling for age, race or ethnicity, alcohol consumption, and smoking, physical activity was inversely related with total BPH (extreme quintiles: OR, 0.75; 95% CI, 0.67-0.85; P for trend, <.001), surgery for BPH (OR, 0.76; 95% CI, 0.64-0.90; P for trend, <.001), and symptomatic BPH (OR, 0.75; 95% CI, 0.64-0.87; P for trend, <.001). Walking, the most prevalent activity, was inversely related to BPH risk; men who walked 2 to 3 h/wk had a 25% lower risk of total BPH. CONCLUSION: Our results indicate that more physically active men have a lower frequency of lower urinary tract symptoms.
Adult↗