Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by ERG tumour protein expression

Graff, Rebecca E.; Meisner, Allison; Ahearn, Thomas U.; Fiorentino, Michelangelo; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A.; Pettersson, Andreas

doi:10.1038/bjc.2016.61

Cited by 19 publications

(25 citation statements)

References 28 publications

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“…A few previous studies have reported positive or no associations, likely due to small sample size or short follow‐up time . Men with diabetes have lower circulating testosterone concentrations, and decreased testosterone may reduce the risk of prostate cancer . Additionally, antidiabetic drugs, such as metformin, can directly influence the prostate cancer growth by inhibiting the proliferation, migration and invasion of the cancer cells .…”

Section: Discussionmentioning

confidence: 99%

“…24,44 Men with diabetes have lower circulating testosterone concentrations, 45 and decreased testosterone may reduce the risk of prostate cancer. 46,47 Additionally, antidiabetic drugs, such as metformin, can directly influence the prostate cancer growth by inhibiting the proliferation, migration and invasion of the cancer cells. 48 In co-twin control analyses, the association of diabetes with prostate cancer became stronger suggesting that some familial factors or genes may partially contribute to the diabetes-cancer association, but cannot fully account for it.…”

Section: Discussionmentioning

confidence: 99%

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Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study

Bao

Pedersen

Yang

et al. 2018

Intl Journal of Cancer

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The association between diabetes and cancer risk remains controversial. Hence, we examined whether midlife diabetes is related to the risk of cancer in late-life, and whether genetic and early-life environmental factors play a role in this association. This study included 25,154 twin individuals born in 1958 or earlier from the Swedish Twin Registry. Information on cancer diagnosis in late life (aged ≥ 65) during 1998-2014, was derived from the National Patient and Cancer Registries. Diabetes was ascertained based on self- or informant-reported history, patient registry and antidiabetic medication use. Midlife diabetes was defined when diabetes was diagnosed before 65 years. Data were analyzed following two strategies: (i) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models, and (ii) co-twin control analysis for cancer-discordant twin pairs using conditional logistic regression. Overall, 1,766 (7.0%) had midlife diabetes and 5,293 (21.0%) had cancer in late-life. In multiadjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95-37.67) for pharynx cancer, 5.78 (1.72-19.40) for small intestine cancer, 2.37 (1.14-4.91) for liver cancer and 0.48 (0.35-0.67) for prostate cancer. In people with diabetes, diabetes duration was dose-dependently associated with cancer risk. In conditional logistic regression analysis of 176 prostate cancer-discordant twin pairs, the association between midlife diabetes and prostate cancer in later life became stronger. Midlife diabetes increases the risk of pharynx, small intestine and liver cancers, but reduces prostate cancer risk in late life. Genetic and early-life environmental factors may partially contribute to the diabetes-prostate cancer association.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study

Bao

Pedersen

Yang

et al. 2018

Intl Journal of Cancer

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“…Briefly, the TMPRSS2:ERG gene fusion is a common molecular subtype of prostate cancer that was characterized using immunohistochemistry for protein overexpression of v‐ets erythroblastosis virus E26 oncogene homolog (ERG), a method that was previously shown to have high concordance with other assays . A genitourinary pathologist reviewed the TMA slides and samples were considered positive if they had at least one core of ERG staining within prostate epithelial cells . Similarly, immunohistochemistry of the tumor suppressor PTEN was performed on TMAs using a rabbit antihuman PTEN antibody (Clone D4.3 XP; Cell Signaling Technologies, Danvers, MA).…”

Section: Methodsmentioning

confidence: 99%

Corpora amylacea in prostatectomy tissue and associations with molecular, histological, and lifestyle factors

et al. 2018

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Background: Corpora amylacea are amyloid bodies commonly found adjacent to damaged prostate epithelium. Little is known about their formation or function. The current study sought to characterize corpora amylacea in prostate tissue and to describe their relationship with clinical, histological, molecular and lifestyle factors, especially with chronic inflammation which is associated with aggressive disease. Methods: We studied a cohort of 355 men with prostate cancer and tissue specimens from the Health Professionals Follow-up Study. Pathologists examined H&E slides and undertook a standardized review for histologic data and inflammation. Trained observers counted corpora amylacea within the benign and predominately tumor areas. Immunohistochemistry biomarkers were available from tissue microarrays. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) to assess associations of chronic inflammation, clinical, histological, molecular and lifestyle factors with the presence of corpora amylacea. Results: Corpora amylacea were present in benign tissue area for 298 men (84%). Specimens with moderate to severe chronic inflammation were more likely to have corpora amylacea in benign regions (OR=5.4 95% CI 1.9, 15.6). Moreover, corpora amylacea were more common in men with higher body mass index (OR=1.13 95% CI 1.01, 1.26). In contrast, Gleason grade (OR=0.4 95% CI 0.2, 0.8), proliferation index (OR=0.6 95% CI 0.3, 1.2) and presence of the TMPRSS2:ERG fusion (OR=0.4 95% CI 0.2, 0.8) were inversely associated with corpora amylacea presence. TURP specimens were less likely to have corpora amylacea than prostatectomy specimens (OR=0.12 95% CI 0.03, 0.47). Age, PSA, stage, biomarkers of angiogenesis and PTEN, and vasectomy were not significantly associated with corpora amylacea. Conclusion: Corpora amylacea were common among men with prostate cancer and were associated with pro-inflammatory factors, some markers of less aggressive disease, and lack of the TMPRSS2:ERG fusion.

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“…The biomarkers identified to date may improve screening for CaP (e.g., as an alternative or supplement to PSA testing) and might inform treatment choices and prognosis. A number of prostate tumor biomarkers have been identified that may define heterogeneity of CaP etiology 59, 60 , have clinical implications for surveillance and treatment (reviewed in 61 ), or correlate with aggressive phenotypes 62-69 . Among these are the TMPRSS2:ERG gene fusion/translocation 70 , Ki-67 expression 64 , biomarkers involved in androgen metabolism 65, 71 and genomic classifiers that use a whole-transcriptome microarray assays to analyze gene activity in prostate cancer specimens 72 .…”

Section: Tumor Biomarkersmentioning

confidence: 99%

“…However, the underlying marker distribution may identify tumor heterogeneity that informs CaP etiology and disparities. For example, it is becoming clear that the relationship of potential CaP risk factors differs by TMPRSS2:ERG translocation status 59, 60, 77 . While not formally evaluating a racially diverse group, Pettersson et al 78 reported that the relationship of obesity and lethal CaP varied by TMPRSS2:ERG translocation status.…”

Section: Tumor Biomarkersmentioning

confidence: 99%

Prostate Cancer Genetics: Variation by Race, Ethnicity, and Geography

Rebbeck

2017

Seminars in Radiation Oncology

236

167

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Prostate cancer rates vary substantially by race, ethnicity, and geography. These disparities can be explained by variation in access to screening and treatment, variation in exposure to prostate cancer risk factors, and variation in the underlying biology of prostate carcinogenesis (including genomic propensity of some groups to develop biologically aggressive disease). It is clear that access to screening and treatment are critical influencers of prostate cancer rates, yet even among geographically diverse populations with similar access to care (e.g., low and medium income countries), African descent men have higher prostate cancer rates and poorer prognosis. To date, the proportion of prostate cancer that can be explained by environmental exposures is small, and the impact of these factors across different racial, ethnic, or geographical populations is poorly understood. In contrast, prostate cancer has one of the highest heritabilities of all major cancers. Numerous genetic susceptibility markers have been identified from family-based studies, candidate gene association studies, and genome-wide association studies. Some prostate cancer loci, including the risk loci found at chromosome 8q24, have consistent effects in all groups studied to date. However, replication of many susceptibility loci across race, ethnicity, and geography remains limited, and additional studies in certain populations (particularly in men of African descent) are needed to better understand the underlying genetic basis of prostate cancer.

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Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by ERG tumour protein expression

Cited by 19 publications

References 28 publications

Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study

Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study

Corpora amylacea in prostatectomy tissue and associations with molecular, histological, and lifestyle factors

Prostate Cancer Genetics: Variation by Race, Ethnicity, and Geography

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