Association of the CYP 17 Gene Polymorphism with the Risk of Prostate Cancer : A Meta-Analysis

A T-to-C polymorphism in the 5 promoter region of the CYP17 gene that encodes the cytochrome P450c17 has been implicated as a risk factor for prostate cancer, but individual studies have been inconclusive or controversial. Therefore we performed a meta-analysis of 10 studies (12 comparisons) with CYP17 genotyping on 2404 patients with prostate cancer and 2755 controls. Overall, the random effects odds ratio (OR) for the A2 (C) versus A1 (T) allele was 1.08 [95% confidence interval (CI), 0.95– 1.22], with some between-study heterogeneity (P 0.04). There was no suggestion of an overall effect either in recessive or dominant modeling of A2 effects, and the comparison of A2/A2 versus A1/A1 also showed no differential susceptibility to prostate cancer (OR, 1.15; 95% CI, 0.91–1.46). No effect of A2 was seen in subjects of European descent (7 comparisons, OR, 1.04; 95% CI, 0.92–1.18, no significant between-study heterogeneity) or Asian descent (2 comparisons, OR, 1.06; 95% CI, 0.66– 1.71; P 0.02 for heterogeneity), whereas A2 increased susceptibility to prostate cancer in subjects of African descent (3 comparisons, OR, 1.56; 95% CI, 1.07–2.28; no between-study heterogeneity). Smaller studies unilaterally showed more prominent genetic effects for A2 than larger studies (P 0.038). The meta-analysis suggests that the CYP17 polymorphism is unlikely to increase considerably the risk of sporadic prostate cancer on a wide population basis, especially in subjects of European descent. Previously reported associations may reflect publication bias, although it is also possible that the polymorphism may be important in subjects of African descent.

[1]  E. Imyanitov,et al.  CYP17 genetic polymorphism in endometrial cancer: are only steroids involved? , 2002, Cancer letters.

[2]  J. Stanford,et al.  A polymorphism in the CYP17 gene and risk of prostate cancer. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[3]  J. Parry,et al.  The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis. , 2002, Mutagenesis.

[4]  R. Burk,et al.  Role of family history and ethnicity on the mode and age of prostate cancer presentation. , 2002, The Prostate.

[5]  J. Carpten,et al.  Linkage and association of CYP17 gene in hereditary and sporadic prostate cancer , 2001, International journal of cancer.

[6]  John M. Colford,et al.  Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine, Second Edition , 2001 .

[7]  C. J. Chen,et al.  Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men. , 2001, Journal of the National Cancer Institute.

[8]  J. Ioannidis,et al.  Replication validity of genetic association studies , 2001, Nature Genetics.

[9]  O. Cussenot,et al.  Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways , 2001, Cancer.

[10]  R. Kittles,et al.  Cyp17 promoter variant associated with prostate cancer aggressiveness in African Americans. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[11]  J. Martens,et al.  NF-1C, Sp1, and Sp3 are essential for transcription of the human gene for P450c17 (steroid 17alpha-hydroxylase/17,20 lyase) in human adrenal NCI-H295A cells. , 2001, Molecular endocrinology.

[12]  P. Kantoff,et al.  The relationship between a polymorphism in CYP17 with plasma hormone levels and prostate cancer. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[13]  T. Katoh,et al.  Impact of genetic polymorphisms of 17‐hydroxylase cytochrome P‐450 (CYP17) and steroid 5α‐reductase type II (SRD5A2) genes on prostate‐cancer risk among the Japanese population , 2001, International journal of cancer.

[14]  G. Colditz,et al.  A polymorphism in CYP17 and endometrial cancer risk. , 2001, Cancer research.

[15]  R A Stephenson,et al.  Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study. , 2001, Journal of the National Cancer Institute.

[16]  M. Marberger,et al.  Association of vitamin D receptor and 17 hydroxylase gene polymorphisms with benign prostatic hyperplasia and benign prostatic enlargement. , 2001, Urology.

[17]  M. Forrest,et al.  The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2) genes and serum androgen concentrations in men. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[18]  I. Thompson,et al.  Association of African-American ethnic background with survival in men with metastatic prostate cancer. , 2001, Journal of the National Cancer Institute.

[19]  J. Ioannidis,et al.  Evolution of treatment effects over time: empirical insight from recursive cumulative metaanalyses. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  W. Trzeciak,et al.  Investigations on the genetic polymorphism in the region of CYP17 gene encoding 5′-UTR in patients with polycystic ovarian syndrome , 2001, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[21]  Taylor Murray,et al.  Cancer Statistics, 2001 , 2001, CA: a cancer journal for clinicians.

[22]  J. Stanford,et al.  Familial prostate cancer. , 2001, Epidemiologic reviews.

[23]  L. Kuller,et al.  A common promotor variant in the cytochrome P450c17alpha (CYP17) gene is associated with bioavailability testosterone levels and bone size in men. , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  A. Hsing Hormones and prostate cancer: what's next? , 2001, Epidemiologic reviews.

[25]  N. Makridakis,et al.  Molecular epidemiology of hormone-metabolic loci in prostate cancer. , 2001, Epidemiologic reviews.

[26]  E. Rimm,et al.  Racial variation in prostate cancer incidence and in hormonal system markers among male health professionals. , 2000, Journal of the National Cancer Institute.

[27]  J. Stanford,et al.  Genetics of prostate cancer: too many loci, too few genes. , 2000, American journal of human genetics.

[28]  T. Habuchi,et al.  Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect. , 2000, Cancer research.

[29]  M. Marberger,et al.  A polymorphism in the CYP17 gene is associated with prostate cancer risk , 2000, International journal of cancer.

[30]  A. Spurdle,et al.  CYP17 promotor polymorphism and ovarian cancer risk , 2000, International journal of cancer.

[31]  A. Spurdle,et al.  CYP 17 PROMOTOR POLYMORPHISM AND OVARIAN CANCER RISK , 2000 .

[32]  C. Wadelius,et al.  Prostate cancer associated with CYP17 genotype. , 1999, Pharmacogenetics.

[33]  Jack A. Taylor,et al.  Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). , 1999, Carcinogenesis.

[34]  M. Pike,et al.  Cytochrome P450c17α Gene (CYP17) Polymorphism Predicts Use of Hormone Replacement Therapy , 1999 .

[35]  P. Lønning,et al.  CYP17 and breast cancer risk: the polymorphism in the 5' flanking area of the gene does not influence binding to Sp-1. , 1999, Cancer research.

[36]  J. Ioannidis,et al.  Recursive cumulative meta-analysis: a diagnostic for the evolution of total randomized evidence from group and individual patient data. , 1999, Journal of clinical epidemiology.

[37]  W. Willett,et al.  The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer. , 1999, Cancer research.

[38]  J. Ioannidis Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. , 1998, JAMA.

[39]  J. Ioannidis,et al.  Quantitative Synthesis in Systematic Reviews , 1997, Annals of Internal Medicine.

[40]  L. Vatten,et al.  Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[41]  R. Williamson,et al.  5' polymorphism of the CYP17 gene is not associated with serum testosterone levels in women with polycystic ovaries. , 1996, The Journal of clinical endocrinology and metabolism.

[42]  M. Stampfer,et al.  Prospective study of sex hormone levels and risk of prostate cancer. , 1996, Journal of the National Cancer Institute.

[43]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

[44]  J. Little,et al.  Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. , 1994, Human molecular genetics.

[45]  T C Chalmers,et al.  Cumulative meta-analysis of therapeutic trials for myocardial infarction. , 1992, The New England journal of medicine.

[46]  P. Easterbrook,et al.  Publication bias in clinical research , 1991, The Lancet.

[47]  W. Miller,et al.  Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): similarity with the gene for P450c21. , 1987, DNA.