Is Benign Prostatic Hyperplasia (BPH) an Immune Inflammatory Disease?

Kramer, Gero; Mitteregger, Dieter; Marberger, Michael

doi:10.1016/j.eururo.2006.12.011

Cited by 430 publications

(423 citation statements)

References 75 publications

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“…npg sex hormones, cytokines and active molecules involved in immune and inflammatory responses [18]. Recently, immunological processes and inflammation have been suggested to have a role in the pathogenesis, and as potential triggers, of prostatic disease progression [3].…”

Section: Discussionmentioning

confidence: 99%

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Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Yoo¹,

Kim²,

Chung³

et al. 2010

Asian J Androl

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The precise aetiology of benign prostatic hyperplasia (BPH) remains unclear; however, it is known that immunological inflammatory processes have a role in the pathogenesis of BPH initiation and progression. Nitric oxide synthase 2 (NOS2) inducible expression is closely correlated with prostatic disease, including prostate cancer and BPH. The aim of this study was to investigate the relationship between NOS2 polymorphisms and BPH. With a cohort of 205 controls and 229 BPH subjects, we genotyped three single nucleotide polymorphisms (SNPs) in the NOS2 gene, including rs2779248 (promoter, −278 T/C), rs10459953 (5′-untranslated region) and rs2297518 (exon 16, missense, Ser608Leu), using direct sequencing and restriction fragment length polymorphism. The genotypic and allelic frequencies between control and BPH subjects were compared, and the associations among the BPH subjects were analyzed. SNPStats, SNPAnalyzer and HelixTree programmes were used to analyze SNPs. There was no association on SNPs between control and BPH subjects. When BPH subjects were analyzed, there was no association on SNPs between the low and high prostate-specific antigen groups. However, one SNP (rs10459953, odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.29-0.65, P < 0.0001, in codominant model; OR = 0.23, 95% CI = 0.12-0.46, P < 0.0001, in dominant model; and OR = 0.46, 95% CI = 0.24-0.86, P = 0.015, in recessive model) was associated with prostatic volume in BPH. We detected a strong association in genotype frequencies of NOS2 SNP (rs10459953) between subjects with small and large prostatic volume in BPH. The result suggests that NOS2 may be associated with prostatic volume in BPH.

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Section: Discussionmentioning

confidence: 99%

“…The prevalence of BPH in Western countries is estimated at 40%-70% and in the Korean population at ∼40% [1,2]. Recent study strongly suggests that BPH is an autoimmune inflammatory disease [3]. In most prostatic diseases, immunological processes and inflammation have a role in the pathogenesis of disease initiation and/or progression.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Yoo¹,

Kim²,

Chung³

et al. 2010

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…However, they concluded that inflammation appeared to be involved in the development of both prostate problems. Others 4,5 have also suggested that inflammation is involved in the development of BPH. The exact cause of BPH remains unknown, and according to Untergasser et al 6 the only two well-established factors associated with BPH are androgens and age.…”

Section: Introductionmentioning

confidence: 99%

Effect of diet and exercise intervention on the growth of prostate epithelial cells

Barnard

Kobayashi

Aronson

2008

Prostate Cancer Prostatic Dis

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Epidemiological studies suggest a positive association between nutrient intake, hyperinsulinemia and risk of Benign prostatic hyperplasis (BPH). This study tests the hypothesis that a low-fat, highfiber diet and daily exercise would lower serum insulin and reduce the growth of serum-stimulated primary prostate epithelial cells in culture. Serum samples were obtained from eight overweight men before and after the Pritikin residential, 2-week diet and exercise intervention and from seven men who were long-term followers of the low-fat, high-fiber diet and regular exercise lifestyle. The serum was used to stimulate primary prostate epithelial cells in culture. Growth was measured after 48 and 96 h and apoptosis after 96 h. At 48 h there was no significant difference in growth within the Pre, 2-week or Long-Term groups. At 96 h growth was significantly reduced in the 2-week (13%) and in the Long-Term (14%) groups compared to the Pre data. At 96 h, apoptosis was not significantly different among the three groups. Fasting insulin was reduced by 30% in the 2-week group and by 52% in the Long-Term group compared to the Pre data. Testosterone was unchanged in the 2-week group. The results of this study indicate that a low-fat, high-fiber diet and daily exercise lowers insulin and reduces growth of prostate primary epithelial cells and suggests that lifestyle may be an important factor in the development or progression of BPH. Future prospective trials should address the effects of this lifestyle modification on BPH symptomatology and progression.

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“…21,22 Quintar et al recently demonstrated that acute inflammation secondary to infection resulted in upregulation and hypertrophy of prostatic epithelial and stromal components. 22 The authors noted smooth muscle hypertrophy, with eventual dedifferentiation into a secretory phenotype, which they postulate may have a role in protection against infection.…”

Section: Radical Prostatectomymentioning

confidence: 99%

“…[23][24][25] Inflammatory infiltrates in BPH demonstrate a shift towards predominantly activated CD4( þ ) T lymphocytes and a milieu of proinflammatory cytokines. 21 This may have implications to and beyond the atypia population.…”

Section: Radical Prostatectomymentioning

confidence: 99%

Prostate atypia: clinical and pathological variables associated with cancer diagnosis on repeat biopsy

Kopp

Parsons

Shiau

et al. 2011

Prostate Cancer Prostatic Dis

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The clinical significance of atypical glands suspicious for malignancy (atypia) on prostate biopsy is unclear. We studied a cohort of 139 patients with atypia who underwent repeat prostate biopsy. We analyzed clinical and pathological variables that may be associated with cancer on repeat biopsy. Cancer was diagnosed in 41 (29%) of patients with atypia: 26 of 41 (66%) were Gleason 6, 20% were Gleason 7 and 7% were Gleason 8 (Gleason o6 not reported). There were no significant associations of age, race, family history, PSA, PSA density (PSAd), number of previous biopsies or time to repeat biopsy with cancer diagnosis. In multivariate regression, histological inflammation was associated with an 85% decreased probability of cancer on repeat biopsy (odds ratio; OR 0.15; 95% confidence interval; CI 0.04-0.57; P ¼ 0.04). Radical prostatectomy was performed in 14 of 41 (34%) patients with cancer; 6 (43%) were Gleason sum X7, 3 (21%) were pT3a and 1 (7%) had lymph node metastases. In conclusion, inflammation was independently associated with a significantly decreased risk of cancer on repeat biopsy. However, some patients with initial atypia have higher-risk prostate cancer. Additional studies are needed to elucidate these associations.

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Is Benign Prostatic Hyperplasia (BPH) an Immune Inflammatory Disease?

Cited by 430 publications

References 75 publications

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Effect of diet and exercise intervention on the growth of prostate epithelial cells

Prostate atypia: clinical and pathological variables associated with cancer diagnosis on repeat biopsy

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