is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. The modulation of its expression by sex ...steroids could contribute to the male predominance of severe infections, and given that
has no known indispensable functions, and inhibitors are available, it is an appealing target for prevention or treatment of respiratory viral infections.
The Epidemiology of Prostate Cancer Pernar, Claire H; Ebot, Ericka M; Wilson, Kathryn M ...
Cold Spring Harbor perspectives in medicine,
12/2018, Letnik:
8, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Prostate cancer is a major cause of disease and mortality among men, and each year 1.6 million men are diagnosed with and 366,000 men die of prostate cancer. In this review, we discuss the state of ...evidence for specific genetic, lifestyle, and dietary factors associated with prostate cancer risk. Given the biological heterogeneity of this cancer, we focus on risk factors for advanced or fatal prostate cancer. First, we provide descriptive epidemiology statistics and patterns for prostate cancer incidence and mortality around the world. This includes discussion of the impact of prostate-specific antigen screening on prostate cancer epidemiology. Next, we summarize evidence for selected risk factors for which there is strong or probable evidence of an association: genetics, obesity and weight change, physical activity, smoking, lycopene and tomatoes, fish, vitamin D and calcium, and statins. Finally, we highlight future directions for prostate cancer epidemiology research.
Aneuploidy drives lethal progression in prostate cancer Stopsack, Konrad H.; Whittaker, Charles A.; Gerke, Travis A. ...
Proceedings of the National Academy of Sciences,
06/2019, Letnik:
116, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Aneuploidy, defined as chromosome gains and losses, is a hallmark of cancer. However, compared with other tumor types, extensive aneuploidy is relatively rare in prostate cancer. Thus, whether ...numerical chromosome aberrations dictate disease progression in prostate cancer patients is not known. Here, we report the development of a method based on whole-transcriptome profiling that allowed us to identify chromosome-arm gains and losses in 333 primary prostate tumors. In two independent cohorts (n = 404) followed prospectively for metastases and prostate cancer-specific death for a median of 15 years, increasing extent of tumor aneuploidy as predicted from the tumor transcriptome was strongly associated with higher risk of lethal disease. The 23% of patients whose tumors had five or more predicted chromosome-arm alterations had 5.3 times higher odds of lethal cancer (95% confidence interval, 2.2 to 13.1) than those with the same Gleason score and no predicted aneuploidy. Aneuploidy was associated with lethality even among men with high-risk Gleason score 8-to-10 tumors. These results point to a key role of aneuploidy in driving aggressive disease in primary prostate cancer.
IMPORTANCE: Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE: To estimate familial risk and heritability of cancer types ...in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 80 309 monozygotic and 123 382 same-sex dizygotic twin individuals (N = 203 691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50 990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. EXPOSURES: Shared environmental and heritable risk factors among pairs of twins. MAIN OUTCOMES AND MEASURES: The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin’s development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS: A total of 27 156 incident cancers were diagnosed in 23 980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). CONCLUSIONS AND RELEVANCE: In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.
The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of ...diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. SIGNIFICANCE: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients.
.
BACKGROUND: Prostate cancer incidence varies 60-fold globally, which suggests the roles of lifestyle and dietary factors in its cause. To our knowledge, a comprehensive assessment of the association ...between fish consumption and prostate cancer incidence and mortality has not been reported. OBJECTIVE: We conducted a meta-analysis of fish intake and prostate cancer by focusing on the incidence of prostate cancer and prostate cancer-specific mortality and included subgroup analyses based on race, fish type, method of fish preparation, and high-grade and high-stage cancer. DESIGN: We searched MEDLINE and EMBASE databases (May 2009) for case-control and cohort studies that assessed fish intake and prostate cancer risk. Two authors independently assessed eligibility and extracted data. RESULTS: There was no association between fish consumption and a significant reduction in prostate cancer incidence 12 case-control studies (n = 5777 cases and 9805 control subjects), odds ratio (OR): 0.85; 95% CI: 0.72, 1.00; and 12 cohort studies (n = 445,820), relative risk (RR): 1.01; 95% CI: 0.90, 1.14. It was not possible to perform a meta-analysis for high-grade disease (one case-control study, OR: 1.44; 95% CI: 0.58, 3.03), locally advanced disease (one cohort study, RR: 0.80; 95% CI: 0.61, 1.13), or metastatic disease (one cohort study, RR: 0.56; 95% CI: 0.37, 0.86). There was an association between fish consumption and a significant 63% reduction in prostate cancer-specific mortality 4 cohort studies (n = 49,661), RR: 0.37; 95% CI: 0.18, 0.74. CONCLUSION: Our analyses provide no strong evidence of a protective association of fish consumption with prostate cancer incidence but showed a significant 63% reduction in prostate cancer-specific mortality.
Background
Zinc supplementation was hypothesized to have therapeutic potential against prostate cancer, but its influence on prostate cancer incidence especially at high doses is controversial.
...Methods
A total of 47,240 men from the Health Professionals Follow-up Study were followed from 1986 to 2016. Men reported their zinc supplement use at baseline and biennially thereafter. Clinical features of prostate cancer included stage, grade, lethal and aggressive (T4 or N1 or M1 or Gleason 8–10) outcome. Multivariable Cox proportional hazards models were used to evaluate the association between zinc supplement use and incidence of prostate cancer.
Results
During a median follow-up of 28.3 years, we documented 6,980 incident prostate cancer cases including 1,053 lethal and 1,143 aggressive. Zinc supplement use was not associated with overall, localized, low- and intermediate-grade prostate cancer. However, compared to never-users, men who used supplement zinc more than 75 mg/day were at higher risk for lethal (HR: 1.76, 95% CI: 1.16–2.66,
P
trend
= 0.001) and aggressive prostate cancer (HR: 1.80, 95% CI: 1.19–2.73,
P
trend
= 0.006). Similarly, men who took supplemental zinc for 15 or more years had a higher risk for lethal (HR: 1.91, 95% CI: 1.28–2.85,
P
trend
<0.001) and aggressive prostate cancer (HR: 1.55, 95% CI: 1.03–2.33,
P
trend
= 0.004).
Conclusion
Zinc supplementation of more than 75 mg per day or over 15 years may substantially increase risk of lethal and aggressive prostate cancer. Caution is warranted regarding excessive usage of zinc supplements among adult men.
Abstract The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical ...recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0–400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1–4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression. Patient summary We examined expression of the RNA molecule SChLAP1 in a large group of prostate cancer patients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease.
PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, ...predominantly surgically treated cohort.
In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided.
On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors.
PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer.
PDF
