Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status

Wright, Jonathan L.; Chéry, Lisly; Holt, Sarah K.; Lin, Daniel W.; Luedeke, Manuel; Rinckleb, Antje E.; Maier, Christiane; Stanford, Janet L.

doi:10.1038/pcan.2015.49

Cited by 15 publications

(26 citation statements)

References 33 publications

(46 reference statements)

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“…Recently, animal studies and clinical observations (2,3) have found that regular doses of aspirin play a role in the prevention and treatment of colitis-associated colorectal cancer, and could reduce mortality in patients with liver metastasis. In addition, aspirin was found to have an inhibitory effect on the growth of esophageal cancer, ovarian cancer, liver cancer, breast cancer, lung cancer, lymphoma and endometrial cancer (4–6).…”

Section: Introductionmentioning

confidence: 99%

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Wang

2016

Oncology Letters

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The aim of the present study was to investigate the effect of aspirin on the cell proliferation and migration of gastric cancer cells in p53-knockout mice. Twenty p53−/− male mice aged 6 to 7 weeks, with an average weight of 20±3 g were used. The model of gastric cancer was established by the implantation of a mouse forestomach carcinoma cell line, subcutaneously, at the back of the neck, and then the mice were randomly divided into two groups after establishment of the model (control group, n=10; experimental group, n=10). Aspirin (250 mg/kg) was added to the food in the experimental group one day before model establishment, until the end of the experiment. Mice in the control group were given regular food without aspirin. All mice were sacrificed 3 months afterwards, and gastric cancer tissues were harvested. MTT assay was used to detect the proliferation of the tumor cells. Tumor cell number was also observed. Migration ability was detected by scratch assay, and E-cadherin protein expression was evaluated by immunofluorescence. The results revealed that the proliferation ability of tumor cells in the experimental group was lower than that in the control group. In addition, cell numbers were significantly decreased and the migration ability was diminished. The expression of E-cadherin was also increased in the experimental group, and the differences were statistically significant (P<0.05). In conclusion, aspirin inhibited the cell proliferation and migration of gastric cancer cells in mice.

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Section: Introductionmentioning

confidence: 99%

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Wang

2016

Oncology Letters

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“…In a study from our group, we found that the intake of tomato sauce, a substantial contributor to lycopene intake, is more strongly associated with ERG‐positive than ERG‐negative prostate cancer . Similarly, Wright and colleagues determined that the use of aspirin, an anti‐inflammatory medication , is associated with a significantly reduced risk of TMPRSS2:ERG positive prostate cancer only . It could be that tomato sauce and aspirin have properties other than antioxidants that contribute to a reduced risk of TMPRSS2:ERG positive disease.…”

Section: Discussionmentioning

confidence: 80%

Circulating Antioxidant Levels and Risk of Prostate Cancer byTMPRSS2:ERG

et al. 2017

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Background Few studies have considered etiological differences across molecular subtypes of prostate cancer, despite potential to improve opportunities for precision prevention of a disease for which modifiable risk factors have remained elusive. Factors that lead to DNA double-strand breaks, such as oxidative stress, may promote the formation of the TMPRSS2:ERG gene fusion in prostate cancer. We tested the hypothesis that increasing levels of pre-diagnostic circulating antioxidants, which may reduce oxidative stress, are associated with lower risk of developing TMPRSS2:ERG positive prostate cancer. Methods We conducted a nested case-control study, including 370 cases and 2,470 controls, to evaluate associations between pre-diagnostic α- and β-carotene, α- and γ-tocopherol, β-cryptoxanthin, lutein, lycopene, retinol, and selenium with the risk of prostate cancer by ERG protein expression status (a marker of TMPRSS2:ERG). Multivariable unconditional polytomous logistic regression was used to calculate odds ratios and 95% confidence intervals. Results We did not find any of the antioxidants to be significantly associated with the risk of prostate cancer according to ERG status. Conclusions The results do not support the hypothesis that circulating pre-diagnostic antioxidant levels protect against developing TMPRSS2:ERG positive prostate cancer. Additional studies are needed to explore mechanisms for the development of TMPRSS2:ERG positive prostate cancer.

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“…Lifestyle may also play a role in the development of PCa defined by TMPRSS2:ERG . For example, lycopene consumption from tomato products has been shown to be inversely associated with ERG‐positive but not ERG‐negative disease, and two studies have shown obesity to be associated with a reduced risk of developing TMPRSS2:ERG ‐positive PCa .…”

Section: Discussionmentioning

confidence: 99%

“…In the most common known molecular subtype (i.e., roughly half of primary PCa), the oncogene ERG fuses with androgen‐regulated promoter genes, most often TMPRSS2 . Although ERG status is unlikely prognostic by itself, several studies have shown that various risk factors are differentially associated with ERG‐defined PCa . In particular, preliminary evidence suggests that there are distinct inherited genetic factors associated with the risk of ERG‐positive versus ERG‐negative disease, lending plausibility to the hypothesis that family history could be differentially associated with the risk of ERG‐defined disease.…”

Section: Introductionmentioning

confidence: 99%

“…6 Although ERG status is unlikely prognostic by itself, 7 several studies have shown that various risk factors are differentially associated with ERG-defined PCa. [8][9][10][11][12][13][14][15][16] In particular, preliminary evidence suggests that there are distinct inherited genetic factors associated with the risk of ERG-positive versus ERG-negative disease, [8][9][10] lending plausibility to the hypothesis that family history could be differentially associated with the risk of ERG-defined disease.…”

Section: Introductionmentioning

confidence: 99%

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Family history of prostate cancer and the incidence of ERG‐ and phosphatase and tensin homolog‐defined prostate cancer

Hashim

Gonzalez‐Feliciano

Ahearn

et al. 2019

Intl Journal of Cancer

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Family history is among the strongest known risk factors for prostate cancer (PCa). Emerging data suggest molecular subtypes of PCa, including two somatic genetic aberrations: fusions of androgen‐regulated promoters with ERG and, separately, phosphatase and tensin homolog (PTEN) loss. We examined associations between family history and incidence of these subtypes in 44,126 men from the prospective Health Professionals Follow‐up Study. ERG and PTEN status were assessed by immunohistochemistry. Multivariable competing risks models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between self‐reported family history of PCa and molecular subtypes of disease. Thirteen percent of men had a positive family history of PCa at baseline. During a median follow‐up of 18.5 years, 5,511 PCa cases were diagnosed. Among them, 888 were assayed for ERG status (47% ERG‐positive) and 715 were assayed for PTEN loss (14% PTEN null). Family history was more strongly associated with risk of ERG‐negative (HR: 2.15; 95% CI: 1.71–2.70) than ERG‐positive (HR: 1.49; 95% CI: 1.13–1.95) disease (pheterogeneity: 0.04). The strongest difference was among men with an affected father (HRERG‐negative: 2.09; 95% CI: 1.64–2.66; HRERG‐positive: 1.30; 95% CI: 0.96–1.76; pheterogeneity: 0.01). Family history of PCa was positively associated with both PTEN null (HR: 2.10; 95% CI: 1.26–3.49) and PTEN intact (HR: 1.72; 95% CI: 1.39–2.13) PCa (pheterogeneity: 0.47). Our results indicate that PCa family history may be positively associated with PCa in all ERG and PTEN subtypes, suggesting a role of genetic susceptibility in their development. It is possible that ERG‐negative disease could be especially associated with positive family history.

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Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status

Cited by 15 publications

References 33 publications

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Circulating Antioxidant Levels and Risk of Prostate Cancer byTMPRSS2:ERG

Family history of prostate cancer and the incidence of ERG‐ and phosphatase and tensin homolog‐defined prostate cancer

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