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Prostate Cancer

Introduction[]

This article will review the existing data on various aspect of Prostate Cancer. It has been well established that Prostate Cancer is the most common cancer in males. But because of its indolent course in many, most males die with prostate cancer and not because of prostate cancer. There has been a great debate in recent years about screening methodology, specifically as it relates to Prostate Specific Antigen (PSA).

It is presumed by this author that the pathophysiology, diagnostics and Associated Diseases and complications should not change based on population differences, but the assumption will need to be scientifically tested.

At first the focus will be on epidemiology, genetics and treatment options.

Epidemiology[]

Please see SAHRI:How_to_Review_the_Literature

PMID 15546245 AUTHORS: Sunny L. Bb Y. Ap K. M H. R S. S M. Ng S. Sh A. Institution: Bombay Cancer Registry, Indian Cancer Society, Mumbai-400 012, India. lizzy_sunny@yahoo.com Title: Cumulative risk and trends in prostate cancer incidence in Mumbai, India. Source: Asian Pacific Journal of Cancer Prevention: Apjcp. 5(4):401-5, 2004 Oct-Dec. Abstract: BACKGROUND: Information relating to cancer incidence trends in a community forms the scientific basis for the planning and organization of prevention, diagnosis and treatment of cancer. We here estimated the cumulative risk and trends in incidence of prostate cancer in Mumbai, India, using data collected by the Bombay Population-based Cancer Registry from the year 1986 to 2000. METHODS: During the 15 year period, a total of 2864 prostate cancer cases (4.7% of all male cancers and 2.4% of all cancers) were registered by the Bombay Population-based Cancer Registry. For evaluation of the trend, we applied a linear regression model based on the logarithm of the observed incidence rates. The annual percentage changes were also computed for the evaluation. Cumulative incidence rates percentages were calculated by adding up the age specific incidence rates at single ages and then expressed as a percentage. RESULTS: Analysis of the trends in age-adjusted incidence rates of prostate cancer during the period 1986 to 2000 showed no statistically significant increase or decrease and the rates proved stable across the various age groups (00-49, 50-69 and 70+) also. The probability estimates indicated that one out of every 59 men will contract a prostate cancer at some time in his whole life and 99% of the chance is after he reaches the age of 50. CONCLUSION: The stability in age adjusted-incidence rates indicates that there are no changes in the etiological factors for prostate cancer in Mumbai, India. These findings may be of general interest because changes in diagnostic practices are confounded in the time trends of prostate cancer change in many western countries preventing inferences on the changes in risk.


PMID 15672937 AUTHORS: Pu YS. Chiang HS. Lin CC. Huang CY. Huang KH. Chen J. Institution: Department of Urology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Title: Changing trends of prostate cancer in Asia. Source: Aging Male. 7(2):120-32, 2004 Jun. Abstract: Although Asian people have the lowest incidence and mortality rates of prostate cancer in the world, these rates have risen rapidly in the past two decades in most Asian countries. Prostate cancer has become one of the leading male cancers in some Asian countries. In 2000, the age-adjusted incidence was over 10 per 100000 men in Japan, Taiwan, Singapore, Malaysia, the Philippines and Israel. Although some of the increases may result from enhanced detection, much of the increased incidence may be associated with westernization of the lifestyle, with increasing obesity and increased consumption of fat. The differences in incidences between native Americans and Asian immigrants are getting smaller, reflecting a possible improvement of diagnostic efforts and changes of environmental risk factors in Asian immigrants. Nevertheless, the huge variations in incidences among ethnic groups imply that there are important genetic risk factors. The stage distributions of prostate cancer in Asian populations are still unfavorable compared to those of Western developed countries. However, a trend towards diagnosing cancer with more favorable prognosis is seen in most Asian countries. Both genetic and environmental risk factors responsible for elevated risks in Asian people are being identified, which may help to reduce prostate cancer incidence in a chemopreventive setting.


PMID 15808953 - the incidence of prostate cancer has risen by 5-118% in the indexed Asian countries (age-specific and age-standardized) [tocheck|which countries?] based on incidence and mortality rates data for prostate cancer in Asian countries for 1978-1997. - Incidence at centres in Japan rose as much as 102% (Miyagi 6.3-12.7 per 100,000 person-years) whilst the incidence in Singaporean Chinese increased 118% from 6.6 to 14.4 per 100,000 person-years. - The lowest incidence rate recorded was in Shanghai, China and the highest rates were in Rizal Province in the Philippines, although still much lower than those in the United States of America (USA) and many European countries. - Whilst the absolute value of the increase is not comparable to North American and European populations, the incidence ratio in many Asian centres is similar to that of the high-risk countries. - The increases in age-adjusted mortality rates per 100,000 person-years, adjusted to the world standard, ranged from 50% in Thailand to 260% in Korea.

- A better understanding of how these factors interact to cause prostate cancer through further studies with a multi-ethnic perspective will facilitate appropriate public health strategies to minimise high-risk factors and maintain protective factors and keep prostate cancer at bay.

- The difference may be partly due to genetic polymorphism in the androgen receptor and androgen metabolism pathway enzymes as well as to dietary or environmental factors. In particular, phytochemicals, such as isoflavonoids and tea polyphenols, which are common in Asian diets showed promising anti-mitotic activity in animal and clinical studies.


PMID 12477151

- __the hypothesis__ that the screening-detected prevalence of prostate cancer is higher among men of African descent than among men of Asian-Indian descent living in Trinidad & Tobago. -- Population-based prostate cancer screening study among men aged 50-64. -- Caribbean islands of Trinidad and Tobago. -- Tobago, population-based sample of 1196 male residents of African descent; Trinidad, 173 agricultural workers of Asian-Indian descent. -- Serum prostate specific antigen (PSA, Abbot AxSYM) and digital rectal exam (DRE) were used to screen men for prostate cancer. -- Men with elevated PSA (> or = 4 ng/mL) and/or abnormal DRE were offered an ultrasound guided sextant biopsy of the prostate gland.

-- MAIN OUTCOME MEASURES: Prevalence of abnormal screen; prevalence of prostate cancer. -- RESULTS: Elevated PSA and/or abnormal DRE were observed in 29% (348/1196) of Afro-Tobagonian men. Three hundred sixteen men underwent biopsies. Screening-detected prostate cancer prevalence was: 4.9% (23/468) for those aged 50-55; 7.7% (28/366) for those aged 55-59; and 13.3% (48/362) for those aged 60-64 years. Screening was abnormal in 18% (31/173) of Asian-Indian men; 25 underwent biopsies. Prostate cancer prevalence in Asian Indian men was: 1.6% (1/63) for those aged 50-54; 1.4% (1/71) for those aged 55-59; and 5.1% (2/39) for those aged 60-64 years. Mantel-Haenszel age-adjusted rate ratio was 3.4, 95% CI 1.3-9.0. CONCLUSIONS: This study establishes a high prevalence of screening-detected prostate cancer among Afro-Tobagonians compared with Indo-Trinidadians. Comparison of candidate genes, environmental, and lifestyle factors between these populations may identify factors that increase risk for, or provide protection against, prostate cancer.


PMID 12015759

Title: The prevalence of high-grade prostatic intraepithelial neoplasia in surgical resection specimens: an Indian experience. Source: Cancer. 94(9):2350-2, 2002 May 1.

Abstract: BACKGROUND: To the authors' knowledge there is a paucity of literature regarding the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) in the Indian subcontinent. The objective of the current study was to document the prevalence of HGPIN in a low-risk Indian population. METHOD: SA total of 110 prostate specimens (61 taken from the test group and 49 taken from the control group) were studied to document the prevalence of HGPIN in a low-risk Indian population. RESULTS: None of the benign prostate samples were found to harbor HGPIN, whereas 85.24% of the samples from malignant prostates did so. CONCLUSION: SA strong correlation between HGPIN and invasive carcinoma was observed, a finding that reinforces the view that HGPIN is a strong indicator of concurrent invasive prostate carcinoma. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10495


PMID 6739372 Title: Carcinoma of the prostate in Israel: some epidemiological and therapeutic considerations.

PMID 12561991

Title: Pattern of cancer in Dayanand Medical College & Hospital, Ludhiana (a ten year retrospective study).

Abstract: A ten year retrospective study was undertaken to ascertain the pattern and incidence of cancer in Ludhiana which is an industrial town with catchment area of Ludhiana consisting of Ludhiana distt., Sangrur, Jalandhar, Hoshiarpur, Faridkot, Ferozepur, Ropar, Kapurthala, some parts of Himachel Pradesh and Haryana. A total number of 56,565 biopsies were received for histopathological examinaiton in 10 years and 4,730 cases of cancer were diagnosed. The incidence of total malignant tumors was 8.36%. Females out numbered males in the incidence of cancer, with male to female ratio being 1:1.09. Most of the cancers were seen in the age group of 41-50 years. In females the two most common cancer sites were breast (21.07%) and cervix (19.4%) while in males hypopharynx--larynx (13.94%) and prostate (9.65%) were the most common sites of cancer.

PMID 8225379 AUTHORS: Kapoor R. Goswami KC. Kapoor B. Dubey VK. Institution: Department of Blood Transfusion, Government Medical College, Jammu, India. Title: Pattern of cancer in Jammu region (hospital based study 1978-'87). Source: Indian Journal of Cancer. 30(2):67-71, 1993 Jun. Abstract: 2681 histologically confirmed cases of cancer (1402 males and 1279 females) were seen during the ten year period 1978 to 1987 in Pathology Department, Government Medical College, Jammu. The relative frequencies of cancer at various primary sites have been determined with respect to age, sex and religion. The majority of cancers were seen between 31-60 years (67.7%) with a peak in 41-50 years age group. Out of the total cancer patients 2,437 were Hindus (90.8%) and 244 were Muslims (9.2%). The most common cancer sites among males were lung, skin, larynx, prostate and lymphnodes. Cancer cervix was the most common tumor in females, followed by cancer breast, gall bladder and uterus. Among Muslims, cancer cervix and penis were infrequent. Cancer lung and larynx were also relatively less frequent in Muslims.


PMID 1464817

Title: Male genital tract tumors in Punjab, India. 1992 Sep-Oct. Abstract: A total of 95,797 tissue specimens were submitted to our laboratory for histopathological examination during the 21-year period from January 1964 to December 1984. Out of 21,281 cases diagnosed as tumors, 9,254 were found in the male population, comprising 6,846 malignant neoplasms and 2,408 benign neoplasms. There were 1,175 tumors of the male genital tract of which 1,118 were malignant and 57 were benign. The incidence of male genital tract cancer represented 16.33% of male malignancies. The relative frequency of malignant tumors of various organs in the male genital tract was penis, 42.49%; prostate, 40.34%; testis, 15.92%; scrotum, 0.71%; epididymis, 0.36%; spermatic cord, 0.09%; and urethra, 0.09%. All these tumors were classified into various histopathological types and their relative frequency was determined. Some of the rare tumors diagnosed included leiomyosarcoma of the penis, transitional cell carcinoma of the prostate gland, orchioblastoma of the testis, and carcinoma of the urethra. A separate study by this department on the pattern of cancer distribution revealed that cancer of the uterine cervix is the most common malignancy in females in this geographic region. We postulate that a common carcinogenic agent, either a virus or a biochemical (smegmatic) factor, may be responsible for the high incidence of carcinoma of the penis in males and carcinoma of the cervix in females. Educating people about the importance of penile hygiene, and, in particular, educating mothers to retract the foreskin of male babies and to wash it with soap and water when bathing them, will hopefully reduce the incidence of these cancers in regions of high prevalence.


PMID 1464811 AUTHORS: Moran EM. Institution: World Institute of Ecology, University of California, Irvine. Title: Epidemiological factors of cancer in California. Source: Journal of Environmental Pathology, Toxicology & Oncology. 11(5-6):303-7, 1992 Sep-Oct. Abstract: California has 12% of the U.S. population. In 1991, the newly diagnosed cancer cases in California represented 10% of all new cancer cases in the country, and the yearly toll was 10% of all cancer deaths. Relative to all new cancer cases in the U.S., California had 10, 9.8, 9.8, and 9.3% of breast, lung, prostate, and colorectal cancers, respectively. Because of its large population and cancer incidence, the epidemiology of cancer in California is of particular interest. Epidemiological factors reviewed in this article include ethnicity, lifestyle, occupation, and environmental conditions. Ethnic factors: There is an increased incidence of cervical and gallbladder cancer among Hispanic women, and of stomach cancer in Hispanic men and women. In U.S.-born Chinese men, the most prevalent cancers are those of the lung and colon, which is also seen in American white men. In U.S.-born Chinese women, there is an upward displacement of breast cancer incidence. In U.S.-born Japanese men and women, the mortality rate is closer to that of American whites. Life-style: Members of the Mormon Church and Seventh-Day Adventists have only 50% of the U.S. standardized mortality rate for cancer associated with smoking. Increased coffee consumption has been found to be associated with increased occurrence of colon and bladder cancer; alcohol use has been reported to have a positive association with colorectal cancer. The large AIDS population in San Francisco has a 144-fold odds ratio of Kaposi's sarcoma and a fivefold odds ratio of lymphoma when compared with the general U.S. population. Occupational factors: An increased incidence of mesothelioma in asbestos workers, of gastric cancer, skin cancer, and lymphoma in men working in dusty environments, and of astrocytoma in individuals with prolonged exposure to low-frequency electric and magnetic fields has been recorded. Environmental factors: The drinking-water pool in northern California is contaminated with asbestos of the serpentine type, which is associated with mesothelioma of the peritoneum and carcinoma of the lung, gallbladder, and pancreas. Petrochemical fumes in the heavily industrialized San Francisco Bay area have not been associated with an increased occurrence of cancer. No significant incidence in cancer has been noted in the counties surrounding the nuclear power plant at San Onofre during 18 years of close observation.



PMID 3878166

AUTHORS: Donn AS. Muir CS. Title: Prostatic cancer: some epidemiological features. Source: Bulletin du Cancer. 72(5):381-90, 1985. Abstract: Prostatic cancer is a frequent tumour in old men. The disease is very common in North America, particularly among Blacks, and in Scandinavia, while it is currently rare in Asian countries. Both morbidity and mortality rates have increased in most areas in recent years, the rate of increase being greatest in populations where the risk has hitherto been low. "Latent" (microscopic) prostatic cancer is much commoner than overt clinical prostatic cancer and, in contrast to the latter, the prevalence is similar in a wide spectrum of countries and ethnic groups. Detection of these latent tumours is dependent on medical care variables. The relationships between tumor development, latency and progression are not understood. It may be useful to consider "latent" prostatic cancer as a separate entity in future classifications and epidemiological research. Hormonal, sexual, dietary, chemical and genetic factors have been implicated in the aetiology although the mechanisms by which they act and the relationships between these factors are not known. As a high fat diet has been found to increase risk in case-control studies, a plausible sequence of events would be a fat-induced change of hormone profile with increased uptake by the prostate of male sex hormones leading to carcinoma--as in the rat. The evidence is however by no means entirely consistent and should be explored further in studies of the US Black and White populations, populations with age-standardized incidence rates in the order of 100 and 50 per 100,000 per annum respectively. If it be accepted that the factors leading to latent carcinoma of prostate are evenly distributed throughout the world, then studies directed at uncovering the agents responsible for progression from latent to clinically invasive state could be rewarding. Such studies would need to be large, prospective in nature and would require a high frequency of autopsy of cohort members to ascertain whether the prostate was cancer free or not. Prevention is not feasible on the basis of current knowledge and further inquiry regarding the aetiopathogenesis of prostatic cancer is needed before preventive approaches can be envisaged.


PMID 7427916

AUTHORS: Jussawalla DJ. Yeole BB. Natekar MV. Rajagopalan TR. Title: Cancer in the Sindhi population of Greater Bombay. Source: Cancer. 46(9):2107-15, 1980 Nov 1.

Abstract: These are the people who were originally inhabitants of the Province of Sind, which formed a part of the large Bombay Presidency in Undivided India before 1947. The Sindhi Hindus migrated en masse to India after partition. An attempt has been made here to examine the differences found in the site-specific cancer risks among the Sindhi community, the other Hindu groups (such as the Marathi and Gujrati populations) and the Parsi community of Greater Bombay. As the Indian Census Board does not provide age distribution details for the Sindhis, analysis of the data was undertaken employing frequency ratios. Age-standardized cancer ratios (ASCAR) were also utilized for certain calculations. The common sites of cancer appear to vary greatly between the total Bombay population and the Sindhi group. In Sindhi men, for example, cancers of the lung, large bowel, prostate, kidneys and leukemias are most commmonly seen, whereas laryngeal and oesophageal cancers predominate in the general population of Bombay. In Sindhi women the breast, uterus, ovary, and skin are the preferred sites, whereas cancers of the cervix and leukemias are predominant in the general population of Bombay. It is interesting to note that there is a degree of similarity in the incidence of cancer at certain anatomical sites, such as the prostate, large intestine, and leukemias in males, and breast, cervix, ovary and uterus in females, between the Sindhi and Parsi communities of Greater Bombay.


PMID 51027 AUTHORS: Higgins IT. Title: The epidemiology of cancer of the prostate. Source: Journal of Chronic Diseases. 28(7-8):343, 1975 Aug.


PMID 4186774 AUTHORS: Matapurkar BG. Taneja OP. Title: Incidence of carcinoma prostate. A five year survey. Source: Indian Journal of Cancer. 6(3):172-83, 1969 Sep.

Genetics[]

SAHRI:PMID 15638917 AUTHORS: Srivastava DS. Mandhani A. Mittal B. Mittal RD. Institution: Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow-226 014, Uttar Pradesh, India. Title: Genetic polymorphism of glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India. Source: BJU International. 95(1):170-3, 2005 Jan. CP England Abstract: OBJECTIVE: To examine the association of glutathione-S-transferase (GST) gene polymorphisms in patients with sporadic prostate cancer, in a North Indian population, as GSTs are active in detoxifying a wide variety of endogenous or exogenous carcinogens, and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 have been assessed to evaluate the relative risk of various cancers. PATIENTS AND METHODS: We assessed 127 patients with prostate cancer and 144 age-matched controls, all from North India. The GSTT1 and GSTM1 null genotypes were identified by multiplex polymerase chain reaction (PCR) in peripheral blood DNA samples, and GSTP1-313 A/G polymorphism was determined by PCR/restriction fragment length polymorphism. RESULTS: There was a significant association in null alleles of the GSTM1 (odds ratio 2.239, 95% confidence interval 1.37-3.65, P = 0.001) and GSTT1 (1.891, 1.089-3.282, P = 0.026) with prostate cancer risk, and in the -313 G alleles (Val) of the GSTP1 gene (2.48, 1.51-4.08, P < 0.001). The combined analysis of these three genotypes showed a further increase in the risks of prostate cancer (7.23, 2.42-22.6, P < 0.001). CONCLUSION: The GSTP1-313 G polymorphism, and null alleles of GSTM1 and GSTT1, are strong predisposing risk factors for sporadic prostate cancer in North India. PT Journal Article.


SAHRI:PMID 14613585 AUTHORS: Banerjee AG. Liu J. Yuan Y. Gopalakrishnan VK. Johansson SL. Dinda AK. Gupta NP. Trevino L. Vishwanatha JK. Institution: Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE 68198, USA. abanerjee@unmc.edu Title: Expression of biomarkers modulating prostate cancer angiogenesis: differential expression of annexin II in prostate carcinomas from India and USA. Source: Molecular Cancer. 2(1):34, 2003 Oct 8. CP England Abstract: BACKGROUND: Prostate cancer (PCa) incidences vary with genetic, geographical and ethnic dietary background of patients while angiogenesis is modulated through exquisite interplay of tumor-stromal interactions of biological macromolecules. We hypothesized that comprehensive analysis of four biomarkers modulating angiogenesis in PCa progression in two diverse populations might explain the variance in the incidence rates. RESULTS: Immunohistochemical analysis of 42 PCa biopsies reveals that though Anx-II expression is lost in both the Indian and American population with Gleason scores (GS) ranging between 6 and 10, up to 25 % of cells in the entire high grade (GS > 8) PD PCa samples from US show intense focal membrane staining for Anx-II unlike similarly graded specimens from India. Consistent with this bservation, the prostate cancer cell lines PC-3, DU-145 and MDA PCa 2A, but not LNCaP-R, LNCAP-UR or MDA PCa 2B cell lines, express Anx-II. Transcriptional reactivation of Anx-II gene with Aza-dC could not entirely account for loss of Anx-II protein in primary PCa. Cyclooxygenase-2 (COX-2) was moderately expressed in most of high grade PIN and some MD PCa and surrounding stroma. COX-2 was not expressed in PD PCa (GS approximately 7-10), while adjacent smooth muscles cells stained weakly positive. Decorin expression was observed only in high grade PIN but not in any of the prostate cancers, atrophy or BPH while stromal areas of BPH stained intensively for DCN and decreased with advancing stages of PCa. Versican expression was weak in most of the MD PCa, moderate in all of BPH, moderately focal in PD PC, weak and focal in PIN, atrophy and adjacent stroma. CONCLUSIONS: Expression of pro- and anti-angiogenic modulators changes with stage of PCa but correlates with angiogenic status. Focal membrane staining of Anx-II reappears in high grade PCa specimens only from US indicating differential expression of Anx-II. COX-2 stained stronger in American specimens compared to Indian specimens. The sequential expression of DCN and VCN in progressive stages was similar in specimens from India and USA indicating no population-based differences. The mechanistic and regulatory role of Anx-II in PCa progression warrants further investigation. PT Journal Article.


SAHRI:PMID 15472409 AUTHORS: Mittal RD. Srivastava DS. Mandhani A. Kumar A. Mittal B. Institution: Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226 014, India. rmittal@sgpgi.ac.in. Title: Polymorphism of GSTM1 and GSTT1 genes in prostate cancer: a study from North India. Source: Indian Journal of Cancer. 41(3):115-9, 2004 Jul-Sep. Abstract: BACKGROUND: Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 genes have been studied earlier to evaluate the relative risk of various cancers. AIM, SETTING AND DESIGN: In the present study, we examined the association of the GSTM1 and GSTT1 gene polymorphisms with sporadic prostate cancer patients in north Indian population. MATERIAL AND METHODS: This case control study was undertaken over a period of 24 months and included 103 prostate cancer patients and 117 controls; both patients and controls originated from northern part of India. The GSTT1 and GSTM1 genotypes were identified by multiplex PCR in peripheral blood DNA samples. STATISTICAL ANALYSIS: Difference in genotype prevalence and association between case and control group were assessed by the Chi square and Fisher Exact tests. RESULTS: Frequencies of null genotypes in GSTT1 and GSTM1, was 11% (13/117) and 30% (35/117) respectively in control individuals. The frequencies of GSTT1 and GSTM1 null genotypes in prostate cancer patients were 34% (35/103) and 53% (55/103) respectively. CONCLUSION: Our study demonstrates that the null genotypes of GSTT1 and GSTM1 are substantially at higher risk for prostate carcinoma as compared to the normal healthy controls. The GSTT1 and GSTM1 null genotypes did not show significant association with tobacco usage in prostate cancer patients. However, the null genotypes were significantly stratified in 50-60 year-old patients when incidence of prostate cancer is high. PT Journal Article.

PMID_12582021

Title: Association of the CYP17 gene polymorphism with the risk of prostate cancer: a meta-analysis. [Review] [47 refs]

Abstract: A T-to-C polymorphism in the 5' promoter region of the CYP17 gene that encodes the cytochrome P450c17alpha 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. [References: 47]

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