***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 and rostanediol glucuronide ( AAG ) levels . We studied the effect of this polymorphism on the risk of prostate cancer in a prospect i ve , 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 can not be completely excluded We examined whether selected polymorphisms in 11 c and i date genes and serum levels of insulin-like growth factor I ( IGF-I ) help predict the presence of prostate cancer among patients prescreened with prostate-specific antigen ( PSA ) and digital rectal exam ( DRE ) .  We studied 1031 consecutive men who underwent one or more prostate biopsies because of an elevated PSA level ( > 4 ng/ml ) or an abnormal DRE . Eleven c and i date genes were examined , including the and rogen receptor , SRD5A2 , CYP17 , CYP3A4 , vitamin D receptor , PSA , GST-T1 , GST-M1 , GST-P1 , IGF-I , and IGF binding protein 3 . We also measured serum IGF-I levels before biopsy . Of the 1031 men , 483 had cancer on any biopsy ( cases ) and 548 men had no cancer ( controls ) . Age , ethnicity , total PSA , and DRE result were strongly predictive of the presence of prostate cancer . The mean IGF-I level for cases ( 119.4 ng/ml ) was lower than for controls ( 124.4 ng/ml , P = 0.05 ) and were not predictive for the presence of prostate cancer . We found no associations between the and rogen receptor , SRD5A2 , CYP17 , CYP3A4 , vitamin D receptor , GST-M1 , GST-P1 , and IGF binding protein 3 genotypes and prostate cancer risk . The adjusted odds ratios for having prostate cancer for patients with the GST-T1 and IGF-I variant alleles were 1.64 ( 95 % confidence interval , 1.1 - 2.4 ; P = 0.01 ) and 1.70 ( 95 % confidence interval , 1.1 - 2.7 ; P = 0.02 ) , respectively . Nine of 11 c and i date genes were not significantly predictive for prostate cancer in a clinical setting . The GST-T1 and IGF-I polymorphisms demonstrated modest associations with prostate cancer risk . IGF-I levels were not helpful in identifying patients with prostate cancer at the time of biopsy Methods of sample size and power calculations are review ed for the most common study design s. The sample size and power equations for these design s are shown to be special cases of two generic formulae for sample size and power calculations . A computer program is available that can be used for studies with dichotomous , continuous , or survival response measures . The alternative hypotheses of interest may be specified either in terms of differing response rates , means , or survival times , or in terms of relative risks or odds ratios . Studies with dichotomous or continuous outcomes may involve either a matched or independent study design . The program can determine the sample size needed to detect a specified alternative hypothesis with the required power , the power with which a specific alternative hypothesis can be detected with a given sample size , or the specific alternative hypotheses that can be detected with a given power and sample size . The program can generate help messages on request that facilitate the use of this software . It writes a log file of all calculated estimates and can produce an output file for plotting power curves . It is written in FORTRAN-77 and is in the public domain In the prostate , the enzyme encoded by the SRD5A2 gene ( 5alpha-reductase ) converts testosterone to dihydrotestosterone , a potent and rogen that has been hypothesized to play a role in the genesis of prostate cancer . Several polymorphisms have been identified in the SRD5A2 gene , including a valine-to-leucine substitution ( V89L ) at codon 89 , a variable number of TA dinucleotide repeats and a missense substitution at codon 49 result ing in an amino acid substitution of alanine with threonine ( A49 T ) . To investigate the influence of these polymorphisms on prostate cancer risk , we conducted a case-control study nested within the Beta-Carotene and Retinol Efficacy Trial . Genotypes were determined by PCR-based capillary electrophoresis using genomic DNA isolated from 300 cases and 300 controls matched on the basis of race , age at enrollment ( within 5 years ) , enrollment study center and year of r and omization . There was no association between V89L genotypes and prostate cancer risk . The age- and race-adjusted odds ratio ( OR ) associated with the VL and LL genotypes were 1.06 ( 95 % confidence interval ( CI ) = 0.75 - 1.49 ) and 0.99 ( 95 % CI = 0.57 - 1.73 ) , respectively , as compared to the VV genotype . The age- and race-adjusted odds ratio for men having 1 TA(9 ) or TA(18 ) allele was 0.98 ( 95 % CI = 0.64 - 1.48 ) when compared to men without TA repeats . The corresponding odds ratio for men without the TA(0 ) alleles was 0.68 ( 95 % CI = 0.21 - 2.19 ) . The age- and race-adjusted odds ratio associated with having at least 1 T allele at codon 49 was 1.11 ( 95 % CI = 0.58 - 2.11 ) , as compared to the AA genotype . Our results do not support the hypothesis that the V89L and A49 T polymorphisms in the SRD5A2 gene are related to the risk of prostate cancer , but are compatible with the suggestion from earlier studies that men who are homozygous for the TA(9 ) or ( 18 ) alleles and men who have the TA(9)/TA(18 ) genotype are at a modestly reduced risk BACKGROUND Prostate cancer is a very common disease in more-developed countries , but its cause is largely unknown . It is an and rogen-dependent cancer , and and rogens have been proposed as having a substantial role in predisposition to the disease . Thus , variations in and rogen metabolism genes may affect risk of this disease . METHODS We screened 216 African-American and 172 Hispanic men with prostate cancer , and 261 African-American and 200 Hispanic healthy men ( controls ) , from a large prospect i ve cohort study ( the Hawaii-Los Angeles Multiethnic Cohort Study ) for a mis-sense substitution in the human prostatic ( or type II ) steroid 5alpha-reductase ( SRD5A2 ) gene , the product of which controls metabolic activation of testosterone to dihydrotestosterone . This mis-sense substitution results in an alanine residue at codon 49 being replaced with threonine ( A49 T ) . We also reconstructed this mutation in the SRD5A2 cDNA , and overexpressed the enzyme in mammalian tissue culture cells . FINDINGS The A49 T aminoacid substitution in the SRD5A2 gene increased the risk of clinical ly significant disease 7.2-fold in African-American men ( 95 % CI=2.17 - 27.91 ; p=0.001 ) and 3.6-fold in Hispanic men ( 1.09 - 12.27 ; p=0.04 ) . The mutant enzyme had a higher in-vitro Vmax than the normal enzyme ( 9.9 vs 1.9 nmol min(-1 ) mg(-1 ) ) . INTERPRETATION The A49 T variant of the SRD5A2 gene may be a significant contributor to the incidence of prostate cancer in African-American and Hispanic men in Los Angeles . We estimate that the population attributable risk due to this aminoacid substitution for clinical ly significant disease is about 8 % in both population s. Increased conversion of testosterone to dihydrotestosterone catalysed by this variant steroid 5alpha-reductase enzyme may be the cause of the increased risk In 1978 the National Prostate Cancer Project launched two protocol s evaluating adjuvant therapy following surgery ( Protocol 900 ) or irradiation ( Protocol 1,000 ) for clinical ly localized prostate cancer . All patients underwent staging pelvic lymphadenectomy . Following definitive treatment , patients were r and omized to either cyclophosphamide 1 gram/m2-IV every 3 weeks for 2 years , estramustine phosphate 600 mg/m2-po daily for up to 2 years , or to observation only .  Patient accession closed in 1985 and includes 184 to Protocol 900 ( 170 evaluable ) and 253 to Protocol 1,000 ( 233 evaluable ) . Lymph node involvement  was identified in 198 patients ( 49 % of total ) , 29 % in Protocol 900 , 63 % in Protocol 1,000 . Median progression-free survival ( PFS ) for patients with nodal involvement in Protocol 1,000 receiving estramustine phosphate adjuvant was longer ( 37.3 mo ) compared to cyclophosphamide ( 30.9 mo ) and to no treatment ( 20.9 mo ) . Median PFS for patients with limited nodal disease in Protocol 1,000 was longer ( 39.9 mo ) , regardless of adjuvant , compared to extensive nodal disease ( 20.7 mo ) . However for patients with extensive nodal involvement , those receiving adjuvant estramustine phosphate experienced a significantly longer median PFS ( 32.8 mo ) compared to adjuvant cyclophosphamide ( 22.7 mo ) and no adjuvant ( 12.9 mo ) . We conclude that adjuvant estramustine phosphate is of benefit in prostate cancer patients with extensive pelvic node involvement receiving irradiation as definitive treatment In the United States , prostate cancer will affect 1 man in 6 during his lifetime . Since the mid‐1980s , screening with the prostate – specific antigen ( PSA ) blood test has more than doubled the risk of a prostate cancer diagnosis . A decrease in prostate cancer death rates has been observed since that time , but the relative contribution of PSA testing as opposed to other factors , such as improved treatment , has been uncertain . The recent release of 2 large r and omized trials suggests that if there is a benefit of screening , it is , at best , small . Methods to assess a man 's risk of prostate cancer , including those tools that integrate multiple risk factors , are now available and should be used in risk assessment . Men undergoing screening for prostate cancer may reduce their risk of prostate cancer  with finasteride . CA Cancer J Clin 2009;59:264‐273 . © 2009 American Cancer Society , Prospect i ve studies suggest that prostate cancer risk may be increased in association with high serum concentrations of free testosterone and and rostanediol glucuronide ( A-diol-g ) . Polymorphisms have been identified in the 17-hydroxylase cytochrome P450 gene ( CYP17 ) and the steroid 5alpha-reductase type II gene ( SRD5A2 ) , two genes that are involved in the bio synthesis and metabolism of and rogens in men . The CYP17 MspA1 I polymorphism has been associated with increased prostate cancer risk , and the SRD5A2 V89L polymorphism has been associated with low A-diol-g in Asian men , a serum marker of 5alpha-reductase activity . The purpose of this study was to investigate the association between these two polymorphisms and serum sex hormone concentrations in 621 British men . In particular , we wanted to test the hypotheses that the A2 allele in the CYP17 gene is associated with increased serum testosterone concentrations , and the L allele in the SRD5A2 gene is associated with reduced A-diol-g concentrations . Mean hormone concentrations were evaluated in each genotype and adjusted for age and other relevant factors . We found no evidence that the CYP17 MspA1 I polymorphism was associated with higher testosterone levels . The L/L genotype of the SRD5A2 V89L polymorphism was associated with a 10 % lower A-diol-g concentration , but this was not significant at the 5 % level . However , the L/L genotype of the V89L polym 
    Output:
    
Analysis of well- design ed population -based studies with pathway-based arrays containing common genetic variants could be useful for identifying genetic factors in prostate cancer