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Urología

#¿El uso de estatinas protege contra la muerte por cáncer de próstata?

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Câncer de Próstata e seus Sintomas, Tratamentos e Curas

COMENTARIO
2/4/2020 Leonard G. Gomella, MD, FACS The Bernard W. Godwin Professor of Prostate Cancer and Chair, Department of Urology, Jefferson Medical College, Senior Director Clinical Affairs, Sidney Kimmel Cancer Center, Jefferson University Hospital.

Entre los hombres de Estados Unidos, el cáncer de próstata es el tipo de cáncer más frecuente y una de las causas más frecuentes de muerte por cáncer. Cada año se diagnostican más de 174 650 casos nuevos y 31 620 personas mueren por cáncer de próstata (estimaciones de 2019). Por lo tanto, los investigadores han buscado desde hace mucho tiempo la forma de prevenir el desarrollo del cáncer de próstata. Se han realizado muchos estudios, pero no se ha descubierto ningún método de prevención eficaz.

Sin embargo, los investigadores han observado desde hace mucho tiempo que los hombres que toman estatinas para reducir el nivel de lípidos en la sangre y ayudar a prevenir la arteriopatía coronaria parecen tener menos probabilidades de morir por cáncer de próstata. Si bien los médicos no están seguros de por qué este fármaco hipocolesterolemiante podría ayudar a prevenir el cáncer de próstata, estos hallazgos han llevado a los investigadores a realizar un estudio a gran escala publicado recientemente sobre el uso de estatinas y el desarrollo de cáncer de próstata.

Los médicos siguieron a más de 40 000 hombres desde 1990 hasta 2014, y observaron si tomaban estatinas, si desarrollaban cáncer de próstata y cuándo lo hacían. En este estudio, se halló que los hombres que tomaban estatinas tenían menos probabilidades de morir por cáncer de próstata. Sin embargo, el estudio no halló ninguna reducción en la cantidad de hombres que desarrollaron cáncer de próstata. Dado que este estudio no asignó aleatoriamente a los hombres a tomar o no estatinas, estos resultados, aunque sugirieron un posible beneficio de las estatinas, no son definitivos. Se necesitan más estudios para determinar si las estatinas son eficaces para prevenir la muerte por cáncer de próstata.

Afortunadamente, el pronóstico de la mayoría de los hombres con cáncer de próstata es muy bueno. La mayoría de los hombres mayores con cáncer de próstata tienden a vivir tanto como otros hombres de su misma edad que tienen una salud general similar y no tienen cáncer de próstata. Los hombres que ya están tomando estatinas como protección contra la enfermedad arterial coronaria pueden obtener un beneficio inesperado al reducir su riesgo de cáncer de próstata. Sin embargo, aún no se sabe si los hombres que no tienen otro motivo para tomar una estatina deberían comenzar a hacerlo únicamente para ayudar a prevenir el cáncer de próstata.

En 2020, nuestra mejor defensa contra la muerte por cáncer de próstata sigue siendo la prueba de detección. La prueba de detección tiene la ventaja de encontrar los tipos de cáncer agresivos en forma temprana, cuando se pueden llegar a curar. Sin embargo, dado que estas pruebas arrojan resultados positivos en muchos hombres que no tienen cáncer y debido a que algunos tipos de cáncer de próstata crecen tan lentamente que, quizás, no necesiten tratamiento, los expertos tienen opiniones diferentes sobre si las pruebas son útiles y cuando es útil realizarlas.

 

MerckManual

#Síndrome geniturinária pós-menopausa, qual melhor tratamento?

Postado em

Paciente se consulta com médica para saber qual melhor tratamento para Síndrome Geniturinária pós-menopausa.

Um estudo clínico randomizado comparou por 6 meses a eficácia e segurança do tratamento com Laser de CO2 fracionado e o uso de creme vaginal a base de estrogênio nos sintomas da síndrome geniturinária pós-menopausa (GSM). Foram incluídas no estudo mulheres na menopausa, com sintomas significativos de atrofia vaginal e excluídas mulheres com prolapsos genitais a partir do grau II, submetidas a cirurgias pélvicas recentes, com infecção genital ativa, histórico de tumores estrogênio dependentes, portadoras de doenças autoimunes, líquen escleroso e plano, doenças crônicas graves e que fizeram algum tipo de tratamento para as queixas de atrofia vaginal no último mês.

Síndrome geniturinária pós-menopausa

atrofia vulvovaginal tem como uma de suas manifestações a síndrome geniturinária da menopausa, caracterizada pela involução do epitélio da vagina e da vulva a partir do declínio do estrogênio característico desta fase. Além disso, mais de 50% das mulheres na menopausa também se queixam de diminuição da elasticidade, ressecamento vaginal, dispareunia, sensação de queimação, coceira e irritação, e queixas urinárias como disúria. Esses sintomas têm impacto negativo significativo na vida sexual e qualidade de vida da mulher.

Resultados

Foram selecionadas 69 pacientes, sendo 34 para o grupo do laser de CO2 vaginal e 35 para o grupo do estrogênio vaginal. Concluiu-se ao final do trabalho de 6 meses que os resultados foram similares com o uso da terapia com laser vaginal e estrogênio vaginal para as queixas geniturinárias, função sexual, sintomas urinários, assim como a satisfação das pacientes com o tratamento proposto.

Estudos sobre o mecanismo de ação do laser de CO2 no epitélio vaginal foram publicados. Em um deles, a avaliação microscópica foi realizada 1 hora após o tratamento com laser e foi possível observar a ativação de agentes regenerativos no tecido conjuntivo, com a formação de novos vasos sanguíneos, e novo colágeno. Essas alterações levam ao remodelamento do tecido vaginal, e aumento da lubrificação, promovendo melhora dos sintomas clínicos da menopausa.

O laser de CO2 mostrou-se seguro e eficaz no tratamento dos sintomas da GSM. Preliminarmente, o laser de CO2 e o estrogênio vaginal resultaram em satisfação do paciente e melhores resultados clínicos. A terapia com laser pode ser considerada para o tratamento a curto prazo da GSM, mas estudos adicionais com acompanhamento a longo prazo, são necessários.

Autor:

 

PebMed

Referências bibliográficas:

  • Paraiso MFR, et al. A randomized clinical trial comparing vaginal laser therapy to vaginal estrogen therapy in women with genitourinary syndrome of menopause: The VeLVET Trial. Menopause: The Journal of The North American Menopause Society. Vol. 27, No. 1, pp. 000-000. DOI: 10.1097/GME.0000000000001416

#Investigação examina solução não invasiva para bexigas hiperativas

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Fonte de imagem: Health Essentials – Cleveland Clinic

Urologistas do Instituto de Medicina Keck da Universidade da Califórnia do Sul estão a lançar um ensaio clínico para avaliar a eficácia da estimulação da espinal medula em pacientes com bexigas hiperativas causadas por problemas neurológicos.

Os investigadores irão utilizar uma técnica chamada Neuromodulação Elétrica Transcutânea da Espinal Medula (TESCoN na sigla em inglês), um tratamento não invasivo que distribui impulsos elétricos de baixa intensidade pela espinal medula.

Uma bexiga hiperactiva causa imensos problemas urológicos, tais como a urinação frequente e a incontinência. Os tratamentos existentes para esta condição podem causar efeitos secundários ou podem necessitar de procedimentos invasivos e altamente especializados.

Segundo Evgeniy Kreydin, líder da investigação que já testou o método, o tratamento é bem tolerado pelos pacientes e fácil de ser administrado por médicos. A estimulação será aplicada por elétrodos colados nas costas do paciente.

Segundo os investigadores, a estimulação reensina as ligações nervosas espinais a suportarem e reterem a urina e a voltar a ter sensibilidade na bexiga. Nos pacientes com lesões neurológicas ou na espinal medula estes nervos estão danificados ou cortados.

O investigador refere que o objetivo da investigação é melhorar a qualidade de vida dos pacientes, visto que uma bexiga hiperativa pode causar desconforto, situações inconvenientes e constrangimento.

Kreydin ainda conclui que quanto mais controlo um paciente tiver sobre a sua bexiga mais controlo terá sobre a sua vida.

#El #ejercicio mejora el #riesgo cardiovascular y la #calidad de vida en pacientes con #cáncer de próstata (BJU Int)

Postado em

Investigadores de la Universidad de Northumbria y de la Universidad de East Anglia (Reino Unido) han demostrado que el ejercicio podría ayudar a los enfermos de cáncer de próstata a punto de iniciar la terapia de privación de andrógenos (ADT).

El tratamiento inicial implica el uso de fármacos o cirugía para reducir el nivel de andrógenos, que las células cancerosas de la próstata suelen requerir para multiplicarse.

“El problema es que la ADT tiene varios efectos secundarios, incluyendo el aumento de la grasa corporal, la disminución de la condición física cardiopulmonar y el aumento de la fatiga. Esto puede aumentar el riesgo de un evento cardiovascular y reducir la calidad de vida relacionada con la salud”, explica Anthony Leicht, uno de los responsables de la investigación, que se ha publicado en el British Journal of Urology.

El equipo examinó a 50 personas para ver si las sesiones de ejercicio supervisadas podían ayudar a reducir los efectos secundarios del ADT y cuánto tiempo duraban los beneficios después de que se retiraba la supervisión del ejercicio. El grupo de ejercicio completó tres meses de entrenamiento supervisado de ejercicios aeróbicos y de resistencia que implicaban dos sesiones semanales de 60 minutos, seguidas de tres meses de ejercicio autodirigido.

Según sus hallazgos, los programas de ejercicio produjeron beneficios sostenidos en el perfil de riesgo cardiovascular y la calidad de vida de los pacientes. Sin embargo, las diferencias en la condición física cardiopulmonar y la fatiga no continuaron después de que el período de ejercicio supervisado terminara.

“Lo importante, y diferente de la mayoría de los otros estudios, fue que los pacientes comenzaron el programa de ejercicios antes de que comenzara el tratamiento de ADT. Otros estudios han examinado a pacientes que ya estaban en tratamiento. En segundo lugar, hicimos un seguimiento durante el período de ejercicio autodirigido y encontramos que algunos de los beneficios eran continuos”, apunta Leicht.

Mantener el programa de ejercicios fue importante porque los efectos secundarios del ADT continúan desarrollándose después de los primeros tres meses de tratamiento. “En las personas mayores a menudo vemos reducciones en la fuerza y la función física solo tres meses después de detener el ejercicio supervisado. Pueden dejar de hacer ejercicio por razones de costo u otras razones. Un enfoque más pragmático como el ejercicio en casa o un período más corto de supervisión con apoyo remoto de seguimiento podría ayudar a sortear estas restricciones y proporcionar beneficios mensurables a los enfermos de cáncer de próstata”, concluye el investigador.

#Electronic-cigarette smoke induces #lung adenocarcinoma and #bladder urothelial hyperplasia in mice

Postado em

Moon-shong TangXue-Ru WuHyun-Wook LeeYong XiaFang-Ming DengAndre L. MoreiraLung-Chi ChenWilliam C. Huang, and Herbert Lepor
  1. Edited by Bert Vogelstein, Johns Hopkins University, Baltimore, MD, and approved September 9, 2019 (received for review July 2, 2019)

Significance

Electronic-cigarette smoke (ECS) is designed to deliver nicotine, and its use is gaining popularity. Previously, we found that ECS induces DNA damage and inhibits DNA repair in the mouse lungs and bladder urothelium. Nicotine induces the same types of DNA adducts and has a similar effect on DNA repair inhibition in human cells. Nicotine also enhances human cells’ mutation and tumorigenic transformation susceptibility. Our current results show that ECS-exposed mice developed lung adenocarcinoma and bladder urothelial hyperplasia, indicating that ECS is a lung carcinogen and a potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, the threat ECS poses to humans is not yet known and warrants in-depth investigation.

Abstract

Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.

 

Tobacco smoke (TS) is a traditional way of delivering nicotine, which is a powerful central nervous system stimulant that provides smokers with instantaneous gratification and leads to long-term tolerance and addiction (1). Unfortunately, in addition to nicotine, TS contains numerous carcinogens generated during tobacco curing and burning (23). For the past few decades, TS has been the leading cause of human cancers (4). In fact, up to 85% of lung cancers and 50% of bladder cancers can be linked to TS (4). Electronic-cigarettes (E-cigs) are an invention designed to deliver nicotine in aerosols via the controlled heating of an organic solution containing nicotine (5). This process avoids tobacco leaves and burning, and generates only aerosols composed of nicotine and the relatively harmless solvents isopropylene glycol and vegetable glycerin. Because of this, E-cigs are promoted as delivering a TS “high” without the known adverse effects, and E-cigs have been adopted as a safe replacement for conventional cigarettes. E-cigs are widely used as a gateway for TS cessation and have even been applied as a therapeutic alternative for reducing TS-related respiratory diseases (56).

It is well established that during the curing and burning of tobacco, nicotine can be transformed into nitrosamines via nitrosation, and that many of these nitrosamines, such as nicotine-derived nitrosamine ketone (NNK) and nitrosonornicotine (NNN), are potent human and animal carcinogens (237). Hence, measuring nitrosamine levels in body fluids has become a gold standard for assessing the potential carcinogenic effect of TS (78). This method has been adapted to address the potential carcinogenic effects of E-cig smoke (ECS) (9). It has been found that the level of 4-(methylnitrosoamino)-4-(3-pyidyl)-1-butanol (NNAL), an NNK derivative, in the urine and saliva of E-cig smokers is only 5% of the levels found in comparable tobacco smokers (9). This has led to the assumption that nicotine nitrosation does not take place in ECS and that only a minute quantity of nitrosamines is present in ECS (9). This finding has supported the recommendation from public health experts, including Public Health England, that E-cigs are 95% safer than conventional cigarettes (10), and has prompted many epidemiologists to speculate that switching from TS to ECS could save millions of lives (11).

Likely as a result of this reasoning, the popularity of E-cig smoking is rising rapidly. Currently 3.2% of adults in the United States and 3.6 million junior-high and high-school students have embraced E-cig smoking (10). Given the widespread use of E-cigs, their health effects—particularly their carcinogenicity—deserve careful scrutiny (10). Assessing the safety of E-cigs must examine 3 critical issues. First, is the level of nitrosamines in the E-cig smokers’ urine, saliva, or blood representative of the carcinogenic effects of ECS? Second, while it is established that TS contains substantial amounts of nitrosamines from nicotine nitrosation during tobacco curing and burning, it is unknown if inhaled nicotine in ECS can be nitrosated and transformed into nitrosamines. In light of the findings that human cells have ample cytochrome p450 enzymes that are able to metabolize nitrosamines rapidly into DNA-damaging products (78), we are confronted with the third and the most important question: Can nitrosamine level in the urine, saliva, and blood represent the extent of nitrosation of inhaled ECS nicotine in vivo?

These questions led us to assess the effects of ECS and nicotine by determining the DNA damage induced by ECS in different organs rather than measuring NNK, NNN, and NNAL in the blood and urine of a mouse model (12). We previously observed that ECS induces mutagenic DNA adducts (cyclic 1,N2-γ-hydroxy-propano-deoxyguanosine [γ-OH-PdG] and O6-methyl-dG) in the lungs, heart, and bladder mucosa and inhibits DNA repair in the lungs in a mouse model (12). We also found that nicotine and NNK both induce the same DNA adducts, impair DNA repair functions, and enhance cell mutational and tumorigenic transformation susceptibility in human lung and bladder epithelial cells (12). Based on these observations, we propose that ECS, as well as nicotine, may induce lung and bladder cancer (12). In this study, we examined the tumorigenicity of ECS in mice.

Methods

ECS Exposure.

A total of 85 male FVB/N mice (6 to 8 wk old; The Jackson Laboratory) were randomly placed into 3 groups. One group (n = 45) was exposed to ECS generated from e-juice (nicotine [36 mg/mL] dissolved in vehicle [Veh; isopolypropylene glycol and vegetable glycerin at a 1:1 ratio]). We maintained the particulate matter concentration in the chamber at 130 mg/m3 and the aerosol nicotine concentration at 0.196 mg/m3 (SI Appendix, Table S1). The second group (n = 20) was exposed to Veh. Aerosols for both groups were generated using an automated 3-port E-cig aerosol generator (e∼Aerosols) set at a constant voltage (1.9 A, 4.0 V) (SI Appendix, Table S1), the same as is done in commercial E-cigs (1213). Mice were subjected to whole-body exposure. The exposure conditions were the same as previously described (12). Mice were exposed for 4 h per day and 5 d per week for 54 wk. The third group (n = 20) remained housed in the animal room, exposed to the ambient filtered air (FA). During the 54-wk period, 3 ECS mice were found dead and 2 ECS mice had to be killed because of inactiveness. No lung tumor was observed in these 5 mice, and 1 was found to have a large intestinal polyp. One Veh-exposed mouse was found dead, and 1 was killed due to a paralyzed leg. Two FA-exposed mice were also found dead. No lung tumor was observed in these 2 Veh and 2 FA mice. At the end of the 54-wk exposure, 40 ECS-exposed, 18 Veh-exposed, and 18 FA-exposed mice survived. The average body weights among these 3 groups were similar (FA group, 34.4 ± 5.84 g; Veh group, 34.0 ± 2.78 g; and ECS group, 35.1 ± 2.99 g; ECS vs. FA, P = 0.67; ECS vs. Veh, P = 0.1998), and all mice appeared healthy. These mice were killed to examine tumor formation in different organs.

Histopathology.

The mice were killed at the end of 54 wk of exposure in accordance with New York University Institutional Animal Care and Use Committee protocols IA17-00048 and 170313-01. The lungs, heart, liver, kidneys, intestine, pancreas, brain, spleen, and bladder were harvested and examined with the naked eye for tumor formation. All organs were immediately fixed in and stored in a 10% formalin solution until section preparation. Slides of lung and bladder samples were prepared and stained with hematoxylin and eosin (H & E) at the Histology Core, New York University Langone Medical Center. In addition to H & E staining, bladder tissue slides were stained with antibodies for the proliferation markers MCM-2 and PCNA and the basal cell marker KRT5 at the New York University Urology Histology Core. All slides were examined independently by 3 pathologists.

Statistical Analysis.

GraphPad Prism 7.0 and 1-way ANOVA with the least significant difference (LSD) post hoc test were used for statistical analysis of lung adenocarcinoma and bladder urothelium hyperplasia formation, respectively, in the 3 groups (ECS, Veh, and FA) of mice.

Results

ECS Induces Lung Adenocarcinoma.

Because it takes over 2 decades for tobacco smokers to develop lung and bladder cancer, and because TS is also related to other human cancers, we examined the tumor formation in different organs after 54 wk of exposure (41415). An examination of the gross anatomy of the mice revealed tumor-like growth in the skin, abdominal cavity, intestines, and lungs. A summary of tumor formation observed in all experimental mice is presented in Table 1. These tumor-like tissues were further examined microscopically. The results show that 9 of 40 (22.5%) mice exposed to ECS developed lung tumors. All lung tumors, subjected to histological examination by 3 pathologists, were identified as adenocarcinomas (Fig. 1). Of these 9 lung tumor-bearing mice, 8 had a single lung adenocarcinoma and 1 formed multiple ipsilateral lung adenocarcinomas (Fig. 1). None of the mice exposed to Veh developed lung tumors. Only 1 of 18 (5.6%) mice exposed to FA had 1 adenocarcinoma formed in the lung. The statistical analyses of lung adenocarcinoma occurrence in ECS-, Veh-, and FA-exposed mice are presented in Tables 2 and 3 and SI Appendix, Table S2 AE. The results show that the higher lung adenocarcinoma incidence in ECS-exposed versus Veh-exposed mice (P = 0.0454), versus the combination of Veh- and FA-exposed mice (P = 0.0154), and versus Veh- and FA-exposed mice (P = 0.0352) is statistically significant.

Table 1.

Tumor-like growth found in different organs of mice exposed to FA, Veh, and ECS*

Table 2.

Lung adenocarcinoma incidence in ECS-, Veh-, and FA-exposed mice

Table 3.

Statistical analysis of lung adenocarcinoma incidence in mice exposed to ECS, Veh, and FA*

ECS Induces Bladder Urothelial Hyperplasia.

Although no visible tumors were detected in the urinary bladders of any of the experimental groups, hyperplastic changes to the bladder urothelium were evident in mice exposed to ECS upon histological examination (Fig. 2). These lesions were either simple or nodular hyperplasia, characterized by a significant increase of urothelial layers (5 to 8 layers compared with 3 layers in the control groups), expansion of Krt5-positive basal urothelial cells, and a distinct elevation of the cell proliferation markers MCM-2 and PCNA (1617). Overall, 23 of 40 (57.5%) ECS-exposed mice, 1 of 16 (6.3%) Veh-exposed mice, and none of 17 (0%) FA-exposed mice developed urothelial hyperplasia (P < 0.001) (Fig. 2). Notably, the frequency of urothelial hyperplasia is slightly higher in mice with lung tumors (6 of 9, 67%) than in mice without lung tumors (18 of 31, 58%), although the difference is not statistically significant (P = 0.64).

Fig. 2.

ECS exposure induces bladder urothelial hyperplasia in mice. Bladder tissues were harvested from the same mice exposed to ECS, Veh, and FA for 54 wk as described in Fig. 1. The tissue slides were prepared for histology examination and stained by H & E or antibodies for proliferation markers MCM-2 and PCNA and basal cell marker KRT5 (200× magnification). (A) Typical staining result of bladder tissues of mice exposed to FA, Veh, and ECS. (B) Histogram presentation of bladder urothelial hyperplasia in mice exposed to FA (n = 17), Veh (n = 16), and ECS (n = 40). Notes: (1) While we were able to examine bladder tissue samples from all 40 ECS-exposed mice, during sample preparation, 1 bladder from FA-exposed mice and 2 from Veh-exposed mice were inadvertently destroyed. (2) The simple (ECS1 mouse) and nodular (ECS2 mouse) hyperplasia had markedly thickened urothelial layers and strong expression of MCM-2, PCNA, and KRT5 (with the latter indicating expansion of basal cells), compared with FA- and VEH-exposed mice, which had very thin urothelial layers with low expression of the proliferation markers.

Discussion

Nicotine carcinogenicity in animal models has been controversial owing to a large number of conflicting results (1820). While different tumor types, including leiomyosarcoma, were observed in animals treated with nicotine via drinking water and subcutaneous injection (1920), many of these results were criticized for their experimental shortcomings and were deemed to be inadequate evidence for an association between nicotine exposure and its effect on carcinogenesis (19). On the other hand, rats exposed to stream air-vaporized nicotine via inhalation for 2 y showed no significant different tumor formation, including lung tumors (21). However, this particular study was also criticized for lacking necessary bioassays and the small number of experimental animals (22 exposed versus 6 control) (19). Despite of all these inconclusive results, the prevailing thinking remains that nicotine is noncarcinogenic (18). In contrast to the results showing that stream air-vaporized nicotine is not lung carcinogenic in rats (21), our results showed that E-cig nicotine induces lung adenocarcinoma in mice. The sources of this discrepancy are unclear. It has been found that the aerosol size of ECS is smaller than the aerosols generated in TS (22). It is likely that the small size of E-cig aerosol allows the ECS nicotine in it to penetrate deeply into lung tissues, inducing DNA damage in bronchioloalveolar cells, whereas the stream air vapors are mainly deposited in the upper aerodigestive linings and tissues, which are rich in antioxidants such as glutathione, glutathione peroxidase, and superoxide dismutase and can effectively neutralize the metabolites of nitrosamines.

We believe that our results support the conclusion that γ-OH-PdG and O6-methyl-dG, the DNA damage induced by metabolites of nicotine nitrosation products, are likely the major causes for lung as well as bladder carcinogenesis in mice (122324). Although no bladder cancers/urothelial carcinomas have been observed, flat and/or papillary urothelial hyperplasia with increased mitotic activity was observed in some of the ECS-exposed mice (SI Appendix, Fig. S1). It should be noted that we found the levels of ECS-induced γ-OH-PdG and O6-methyl-dG in bladder mucosa were only one-fourth and one-fifth of the amount found in the lung tissues, respectively, in mice (12). These results raise the possibility that a longer exposure and/or higher doses of ECS are needed in order for the bladder mucosa to accumulate a sufficient level of γ-OH-PdG– and O6-methyl-dG–induced mutations that could trigger bladder tumorigenesis compared with lung carcinogenesis. We previously observed that mice with increased susceptibility to ECS-induced DNA adduct formation in the lungs are also more susceptible to ECS-induced DNA damage in the bladder (12). In the present study, mice more susceptible to ECS-induced lung tumorigenesis were not more prone to developing urothelial hyperplasia, suggesting that ECS-induced lung tumorigenesis and urothelial hyperplasia are divergent events.

In summary, we showed that ECS exposure of mice induces lung cancer and bladder urothelial hyperplasia. These observations, combined with our previous findings (12) that ECS induces γ-OH-PdG and O6-methyl-dG adducts in the lungs and bladder urothelium and inhibits DNA repair in lung tissues in mice, and that nicotine and NNK induce the same types of DNA adducts and DNA repair inhibition effect and sensitize mutational and tumorigenic cell transformation susceptibility in the human lung epithelial and urothelial cells, indicate that ECS, as well as nicotine and NNK, is a lung carcinogen and a potential bladder carcinogen in mice. It should be noted that TS is a most dangerous environmental agent to which humans are commonly exposed and that ECS may or may not pose any danger to humans. The public should not equate the risk of ECS with that of TS. Our data simply suggest, on the basis of experimental data in model systems, that this issue warrants in-depth study in the future.

Acknowledgments

We thank K. Galdane, E. Halzack, A. Chu, M.-w. Weng, and S. H. Park for technical assistance, and Drs. J. Goldberg, J.-S. Hwang, and M.-w. Weng for statistical analysis. Research was supported by NIH Grants, RO1190678, 1PO1CA165980, P30CA16087, and ES00260.

Footnotes

  • Author contributions: M.-s.T., X.-R.W., L.-C.C., W.C.H., and H.L. designed research; M.-s.T., H.-W.L., Y.X., F.-M.D., and A.L.M. performed research; M.-s.T. and Y.X. contributed new reagents/analytic tools; M.-s.T., X.-R.W., H.-W.L., Y.X., F.-M.D., A.L.M., L.-C.C., W.C.H., and H.L. analyzed data; and M.-s.T., X.-R.W., H.-W.L., Y.X., F.-M.D., A.L.M., L.-C.C., W.C.H., and H.L. wrote the paper.

  • The authors declare no competing interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1911321116/-/DCSupplemental.

References

#Cáncer renal: Un nuevo panorama para ‘el gran desconocido’

Postado em

La introducción de los antiangiogénicos primero y de la inmunoterapia después ha cambiado la historia del cáncer renal. Sobre este y otros aspectos se habló en el último coloquio #MásQuePacientes.

Séptimo tumor en incidencia en España, el cáncer renal sigue siendo “un gran desconocido” que además, hasta hace poco, contaba con escasas opciones de tratamiento. Para profundizar en sus características y analizar el cambio que se ha producido en su abordaje, cuídateplus, en colaboración con Alianza Merck-Pfizer y diario médico, reunió a profesionales y pacientes en una nueva edición del coloquio #MásQuePacientes, ¿Qué hay de nuevo en cáncer renal?, en el que participaron Ana Royo, directora del Área de Oncología e Inmuno-Oncología de Merck; Cecilia Guzmán, directora médico de Oncología de Pfizer; Ana González, psicóloga responsable de Programas de la AECC Madrid; Teresa Alonso, del departamento de Oncología Médica del Hospital Ramón y Cajal; y Antonio Lagares, paciente de cáncer renal.

El siguiente paso será combinar antiangio-génicos e inmunoterapia para aumentar la super-vivencia

“El tipo más frecuente (el 90%) es el carcinoma de células claras, que es el que ha centrado hasta el momento la mayor parte de la investigación. Aunque se sigue llegando al diagnóstico muchas veces por casualidad, a través de una prueba de imagen abdominal por otra causa, sí se ha avanzado mucho respecto a su clasificación, y cada vez se está dando más relevancia a esos subtipos histológicos menos frecuentes, buscando un tratamiento más personalizado”, explicó Teresa Alonso.

Un 20% de los diagnósticos se realizan en enfermedad avanzada, “y es en éstos donde se ha producido una mayor revolución, sobre todo en la última década, con la aparición de nuevos tratamientos”, añadió Alonso.

Terapias: Las líneas actuales han supuesto un giro de 180º en el tratamiento

Para Ana González, el desconocimiento que rodea a esta enfermedad y lo inespecífico de los síntomas favorece que el impacto del diagnóstico sea mayor que en otros tumores. “A ello hay que unir la idea generalizada de que ‘no se puede vivir sin un riñón’, lo que genera mucha incertidumbre tanto respecto a la supervivencia como a la calidad de vida”.
Ana Royo comentó que, a pesar de la intensa investigación actual, aún se desconoce la causa exacta de este tumor, “pero sí se sabe que su origen es multifactorial. El 95% son esporádicos y alrededor del 5% son hereditarios. También se han identificado factores de riesgo que favorecen su aparición y desarrollo, principalmente los cardiovasculares y otros menos frecuentes como la exposición a ciertos químicos”.

Antiangiogénicos

Cecilia Guzmán explicó que durante mucho tiempo estos pacientes disponían de pocas opciones terapéuticas, y las que había eran muy antiguas (citocinas), un panorama que experimentó un giro de 180º con los antiangiogénicos, “que han cambiado la historia natural de la enfermedad, y este logro tiene ahora continuidad con el desarrollo de nuevas opciones de inmunoterapia aplicadas a este tumor. El siguiente paso es la combinación de los antiangiogénicos y la inmunoterapia, una opción que puede aumentar la supervivencia y, también, la calidad de vida”.

Investigación: Combinar inmunoterapia y antiangiogénicos, próximo paso

Teresa Alonso hizo hincapié en la importancia de este cambio de paradigma, que vino determinado por la necesidad de identificar otras dianas terapéuticas sobre las que actuar para tratar a estos pacientes, sobre todo en enfermedad avanzada, en los que el pronóstico era realmente malo. “Gracias a los avances en el estudio de la biología del tumor se llegó al gran hito de los antiangiogénicos, que supuso poder ofrecer tratamientos específicos. Y el segundo hito es la entrada de una inmunoterapia nueva, con una tolerancia excelente. Esto nos ha situado en un escenario realmente esperanzador que esperemos que siga mejorando”.

Alonso comentó que las líneas actuales de investigación se centran principalmente en las vías angiogénica e inmune. “Se están investigando los mecanismos que tiene la célula tumoral para actuar y defenderse ante situaciones de estrés, buscando terapias que actúen a este nivel. Otra línea (de la que esperamos tener resultados pronto) es la que se centra en el metabolismo celular”.

Abordaje:  El enfoque de este tumor debe ser multidisciplinar y personalizado

Los expertos destacaron el importante papel de la industria y la implicación de los especialistas en conseguir estos avances, así como la relevancia de los ensayos clínicos. “Hay que acabar con la idea de ‘conejillo de indias’; estos ensayos suponen una ventaja para los pacientes, ya que las pruebas de control son mucho más exhaustivas. Y, además, con ello se contribuye al desarrollo de nuevas moléculas que pueden ayudar a otros pacientes en el futuro”, afirmó Antonio Lagares.

Los participantes de este #MásQuePacientes también coincidieron en la necesidad de que el enfoque de este tumor sea multidisciplinar. “Hay que hacer una valoración integral de los pacientes, no limitarse a ponerles un tratamiento. Debe ser un abordaje en equipo en el que intervenga la industria farmacéutica, enfermería, asociaciones, psicólogos… Con estas sinergias y engranajes llegaremos mucho más lejos de lo que lo estamos haciendo ahora”, concluyó Teresa Alonso.

#New Guideline for #Testosterone Treatment in Men With ‘Low T

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Nicola M. Parry, DVM

The American College of Physicians (ACP) has released new clinical guidelines providing practical recommendations for testosterone therapy in adult men with age-related low testosterone.

The evidence-based recommendations target all clinicians and were published online January 6 in Annals of Internal Medicine, highlighting data from a systematic review of evidence on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone.

Serum testosterone levels drop as men age, starting in their mid-30s, and approximately 20% of American men older than 60 years have low testosterone.

However, no widely accepted testosterone threshold level exists that represents a measure below which symptoms of androgen deficiency and adverse health outcomes occur.

In addition, the role of testosterone therapy in managing this patient population is controversial.

“The purpose of this American College of Physicians (ACP) guideline is to present recommendations based on the best available evidence on the benefits, harms, and costs of testosterone treatment in adult men with age-related low testosterone,” write Amir Qaseem, MD, PhD, MHA, from the American College of Physicians, Philadelphia, Pennsylvania, and colleagues.

“This guideline does not address screening or diagnosis of hypogonadism or monitoring of testosterone levels,” the authors note.

In particular, the recommendations suggest that clinicians should initiate testosterone treatment in these patients only to help them improve their sexual function.

According to the authors, moderate-certainty evidence from seven trials involving testosterone treatment in adult men with age-related low testosterone showed a small improvement in global sexual function, whereas low-certainty evidence from seven trials showed a small improvement in erectile function.

By contrast, the guideline emphasizes that clinicians should avoid prescribing testosterone treatment for any other concern in this population. Available evidence demonstrates little to no improvement in physical function, depressive symptoms, energy and vitality, or cognition among these men after receiving testosterone treatment, the authors stress.

ACP recommends that clinicians should reassess men’s symptoms within 12 months of testosterone treatment initiation, with regular re-evaluations during subsequent follow up. Clinicians should discontinue treatment in men if sexual function fails to improve.

The guideline also recommends using intramuscular formulations of testosterone treatment for this patient population instead of transdermal ones, because intramuscular formulations cost less and have similar clinical effectiveness and harms.

“The annual cost in 2016 per beneficiary for TRT [testosterone replacement therapy] was $2135.32 for the transdermal and $156.24 for the intramuscular formulation, according to paid pharmaceutical claims provided in the 2016 Medicare Part D Drug Claims data,” the authors write.

In an accompanying editorial, E. Victor Adlin, MD, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, notes that these new ACP guidelines mostly mirror those recently proposed by both the Endocrine Society and the American Urological Association.

However, he predicts that many clinicians will question the ACP’s recommendation to favor use of intramuscular over transdermal formulations of testosterone.

Although Adlin acknowledges the lower cost of intramuscular preparations as a major consideration, he explains that “the need for an intramuscular injection every 1 to 4 weeks is a potential barrier to adherence, and some patients require visits to a health care facility for the injections, which may add to the expense.”

Fluctuating blood testosterone levels after each injection may also result in irregular symptom relief and difficulty achieving the desired blood level, he adds. “Individual preference may vary widely in the choice of testosterone therapy.”

Overall, Adlin stresses that a patient–clinician discussion should serve as the foundation for starting testosterone therapy in men with age-related low testosterone, with the patient playing a central role in treatment decision making.

This guideline was developed with financial support from the American College of Physicians’ operating budget. Study author Carrie Horwitch reports serving as a fiduciary officer for the Washington State Medical Association. Jennifer S. Lin, a member of the ACP Clinical Guidelines Committee, reports being an employee of Kaiser Permanente. Robert McLean, another member of the committee, reports being an employee of Northeast Medical Group. The remaining authors and the editorialist have disclosed no relevant financial relationships.

Ann Intern Med. Published online January 6, 2020. Full textEditorial

#Infections urinaires : quelle #antibiothérapie en cas de #bactéries multirésistantes?

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Paris, France — Lors du 113ème congrès de l’AFU , une session a été dédiée à la problématique de l’antibiorésistance et de ses conséquences dans la prise en charge en particulier des infections urinaires [1]. L’occasion de revenir sur l’évolution des pratiques quotidiennes dans le choix des antibiotiques face à une suspicion d’infection par entérobactéries résistantes aux bêta-lactamines (EBLSE) ou aux carbapénèmes, des bactéries classées multi-résistantes (BMR) ou hautement résistantes (BHR).

Ces dernières années, l’épidémiologie des bactéries résistantes s’est largement modifiée, avec la progression préoccupante en ville des infections à bactéries sécrétrices de bêta-lactamases à spectre élargi (EBLSE), résistantes à plusieurs antibiotiques de la famille des bêta-lactamines (pénicillines, quinolones, fluoroquinolones, céphalosporines de troisième génération…), ce qui amène à revoir l’approche par antibiothérapie.

Longtemps limitée au milieu hospitalier, « les résistances bactériennes sont devenues quasiment aussi fréquentes en ville qu’à l’hôpital », a souligné le Dr Franck Bruyère (Tours) lors de sa présentation. « Aujourd’hui, on ne peut plus affirmer que les infections en milieu communautaire sont plus sensibles [aux antibiotiques] que les infections nosocomiales. »

Les résistances bactériennes sont devenues quasiment aussi fréquentes en ville qu’à l’hôpital. Dr Franck Bruyère

Stagnation des résistances aux quinolones

Si les résistances aux quinolones, notamment à la ciprofloxacine (Ciflox®), commencent à stagner, « preuve de l’efficacité des recommandations de bonnes pratiques » émises pour réduire leur consommation, « l’évolution des infections par EBLSE est sérieusement préoccupante », a commenté le chirurgien urologue.

Auparavant, devant une infection, l’approche probabiliste – qui consiste à prescrire une antibiothérapie avant même de connaitre la sensibilité du germe responsable – amenait à choisir une quinolone (ciprofloxacine ou ofloxacine) ou une céphalosporine de troisième génération (C3G) (ceftriaxone ou céfotaxime) pour plus de sécurité, rappelle-t-il. « C’est désormais terminé », le risque étant d’accentuer encore davantage les résistances aux C3G.

« Dans certaines zones, la prévalence des infections résistantes aux C3G ont dépassé les 10% ». Avec une approche probabiliste, qui implique l’utilisation d’un traitement efficace dans plus de 90% des cas, « on peut alors se retrouver sans antibiotiques à disposition », a commenté le Dr Bruyère.

Dans certaines zones, la prévalence des infections résistantes aux C3G ont dépassé les 10%. Dr Franck Bruyère

Traitement probabiliste limitée à quelques molécules

Selon une récente étude observationnelle multicentrique, dont les résultats ont été présentés lors du dernier congrès d’infectiologie ECCMID 2019, la prévalence de la résistance des souches urinaires EBLSE dans les infections communautaires en France est de 6,6% [2]. En Ile-de-France, elle est presque deux fois plus élevée que dans le reste du pays, avec un taux à 8,5%, contre 4,1% en province.

Dans le cas d’une infection urinaire communautaire (hors infection nosocomiale) à entérobactéries, le traitement probabiliste se limite désormais à quelques molécules, a rappelé le Dr Jean-Ralph Zahar (Hopital universitaire Paris site Avicenne, AP-HP, Bobigny), lors d’une précédente intervention. Selon lui, deux molécules sont encore efficaces contre ces infections: le pivmecillinam (Selexid®) et l’amikacine (Amiklin®).

Les dernières recommandations sur la prise en charge d’une cystite aiguë chez la femme préconisent en antibiothérapie probabiliste la fosfomycine associé au trométamol (Monuril®) en première ligne (dose unique) et le pivmecillinam en seconde intention pendant cinq jours. L’examen cytobactériologique des urines (ECBU) est nécessaire pour un éventuel troisième choix. Les fluoroquinolones ne sont plus recommandées.

S’adapter aux résistances locales

Pour le Dr Bruyère, il est aussi indispensable de tenir compte de l’incidence des résistances bactériennes dans les centres où les patients sont pris en charge, afin d’adapter l’antibiothérapie, mais aussi au niveau régional. « Il faut suivre les recommandations nationales, mais aussi s’adapter aux spécificité locales », a confirmé le Dr Maxime Vallée (CHU de Poitiers), coordonnateur de cette session

Concernant la prévalence des résistances bactériennes, il existe notamment un gradient Nord/Sud en France, mais aussi en Europe, les régions du Sud étant, par exemple, beaucoup plus confrontées à des résistances aux quinolones que celles du Nord. « Il n’est pas tout-à-fait juste d’affirmer qu’il n’est pas possible d’utiliser la ciprofloxacine. C’est vrai au Sud de la France, où on compte 30 à 40% de résistances aux quinolones, mais pas au Nord », estime le Dr Bruyère.

Le chirurgien urologue rappelle toutefois que l’utilisation de quinolones favorise particulièrement l’émergence de résistances. « Ce sont des molécules qui exercent une forte pression de sélection. Avec un seul comprimé, on peut induire une résistance. Il suffit de donner deux comprimés pour que le patient devienne ensuite résistant aux quinolones. »

Outre sa capacité à générer facilement des résistances, les quinologues et les fluoroquinologues sont aussi associés à des effets secondaires sévères, notamment musculaires, qui peuvent être persistantes. L’Agence européenne du médicament (EMA) a, en conséquence, demandé, fin 2018, que les quinolones ne soient plus utilisées et que l’usage des fluoroquinolone (dont le ciprofloxacine) soit restreint.

La prise en charge d’une infection doit aussi tenir compte de certains facteurs liés à un risque accru de résistance. Dans le cas de la résistance aux quinolones, les facteurs de risque sont les suivants:

  • origine nosocomiale de l’infection;
  • exposition antérieure aux fluoroquinolones;
  • présence d’une maladie obstructive affectant l’appareil urinaire;
  • résidence dans un établissement de long séjour.
L’utilisation de quinolones favorise particulièrement l’émergence de résistances. Dr Franck Bruyère

Tenir compte des facteurs de risque

Pour ce qui de l’infection à entérobactéries EBLSE résistantes aux C3G, les facteurs à prendre en compte sont:

  • l’exposition à un antibiotique (amoxicilline/acide clavulanique, C2G, C3G, fluoroquinolones) dans les trois mois précédents;
  • une infection nosocomiale ou liée aux soins;
  • un antécédent de colonisation ou d’infection à EBLSE dans les trois mois;
  • un voyage à l’étranger dans les trois mois dans les zones géographiques à risque (continent indien, Asie du Sud-est, Moyen Orient et Afrique du nord et bassin méditerranéen);
  • une anomalie fonctionnelle ou organique de l’arbre urinaire (en cas d’infection urinaire).

Infection à EBLSE et carbapénèmes

En cas de suspicion d’infection à EBLSE, il est possible de traiter avec des antibiotiques de la classe des carbapénèmes, mais là encore, avec un risque d’induire une résistance à une classe d’antibiotiques qui reste réservée aux cas les plus sévères. Et, en cas de résistance aux carbapénèmes, le clinicien se retrouve sans bêtalactamine efficace à disposition.

« L’infection par des bactéries résistantes aux carbapénèmes reste heureusement rare, mais il faut s’y préparer », a souligné le Dr Aurélien Dinh (hôpital Raymond-Poincarré, Garches), en guise d’introduction de sa présentation consacrée à la prise en charge de ces infections. En cas de suspicion de résistance au BLSE, « le maître mot est la gravité », précise-t-il.

En effet, en l’absence de signes de gravité, la présence d’un facteur de risque d’infection à entérobactéries résistantes aux C3G ne justifie pas la prescription de carbapénème. Selon les dernières recommandations de la Société de pathologie infectieuse de langue française (Spilf), un carbapénème est recommandé en probabiliste dans le traitement des infections urinaires communautaires ou associées aux soins:

  • en cas de choc septique et uniquement avec un facteur de risque de BLSE
  • en cas de sepsis grave si antécédent de BLSE urinaire dans les six mois
L’infection par des bactéries résistantes aux carbapénèmes reste heureusement rare, mais il faut s’y préparer. Dr Aurélien Dinh

Rétrograder l’antibiothérapie

« Lorsque l’infection à EBLSE est confirmée et que les résultats de l’antibiogramme sont connus, il ne faut pas hésiter à rétrograder l’antibiothérapie », ajoute le Dr Dinh. « On peut opter pour un autre antibiotique auquel la souche est sensible ». L’intérêt de substituer un carbapénème par une quinolone reste toutefois débattu, précise-t-il.

Les infections à bactéries porteuses de carbapénémases restent pour le moment des pathologies majoritairement importées. Le voyage à l’étranger dans un pays d’Asie est le facteur de risque majeur. « Si un patient se présente avec une pyélonéphrite aiguë et une diarrhée au retour d’Inde, où il a mangé local, vous pouvez être assuré qu’il est infecté par une bactérie résistante aux carbapénémes », précise le praticien.

En cas de suspicion d’infection de ce type, « le patient doit être isolé pour éviter les transmissions croisées ». Les options thérapeutiques restent limitées. Il est possible d’utiliser la colistine, la tigécycline, « sans savoir si celle-ci est réellement efficace », ou encore la fosfomycine, « dont l’utilisation doit être justifiée auprès de l’ANSM » et l’aminoside, « qui a tendance à altérer les reins ».

« La décision est à prendre selon l’état du patient, en concertation avec le microbiologiste et selon l’arsenal thérapeutique à disposition ». En probabiliste, si le patient est dans un état grave et qu’il revient d’Asie du Sud-Est, « il faut, à mon avis, prescrire à forte dose l’association ceftazidime/avibactam, avec la colistine, l’aztréonam et éventuellement l’aminoside ».

L’association ceftazidime/avibactam (Zavicefta®), qui combine une céphalosporine et une nouvelle molécule inhibitrice de bétalactamase, « devrait devenir le traitement de référence des bactéries porteuses de carbapénémases », a précisé le Dr Dinh.

 

#Novo método de diagnóstico de infertilidade masculina

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Fonte de imagem: mujer.com.pa

Investigadores internacionais liderados por Michael Skinner, da Universidade do Estado de Washington, descobriram um método mais eficaz de diagnosticar a infertilidade masculina.

Segundo o estudo, cerca de 20% dos homens que solicitam a fertilização in vitro têm problemas de infertilidade cuja causa é desconhecida. Estes homens, antes de propostos para tratamento, são sujeitos a um ano ou mais de tentativa de conceção natural com as suas parceiras.

O método corrente de diagnóstico de infertilidade masculina passa por avaliar a quantidade e motilidade dos espermatozoides, o que tem tido um sucesso limitado em separar os homens férteis dos inférteis.

A equipa começou então a tentar encontrar uma forma mais eficaz de diagnóstico, de forma a minimizar o tempo de espera e aumentar a fiabilidade dos tratamentos.

Foram usadas técnicas de análise molecular avançadas para ver se conseguiam identificar alterações ou biomarcadores nos grupos de metil agarrados ao ADN do esperma de homens férteis e inférteis.

A equipa descobriu que todos os homens inférteis do estudo tinham um biomarcador específico que os homens férteis não tinham. Foi também encontrado outro biomarcador que poderá determinar que homens inférteis serão responsivos a tratamentos de terapia hormonal.

“Ter um diagnóstico que diz de imediato se o paciente é infértil” e quais os tratamentos que funcionarão seria extremamente útil, conclui Skinner.

NotíciasdaSaúde

#Physical activity may protect against prostate cancer

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Researchers using a new method of assessing risk factors for prostate cancer have found an intriguing link between a lack of physical activity and an increased risk of this condition.

man jogging in parkShare on Pinterest
New evidence suggests that being physically active could help slash prostate cancer risk.

Prostate cancer is the second most common type of cancer among males both in the United StatesTrusted Source and worldwideTrusted Source.

According to data from the National Cancer Institute (NCI), by the end of 2019, there will have been an estimated 174,650 new cases of prostate cancer in the U.S. alone.

Despite the number of people that this cancer affects every year, specialists still have insufficient knowledge about the risk factors that may play a role in its development.

The NCI cite a mix of modifiable and nonmodifiable factors, including age, a family history of prostate cancer, and the levels of vitamin E, folic acid, and calcium in the body.

Yet there may be other lifestyle-related factors at play, and investigators are hard at work to uncover them.

Recently, a team of researchers from the University of Bristol and Imperial College London in the United Kingdom — alongside colleagues from other academic institutions across the globe — have used a different approach to try to find out more about prostate cancer risk factors.

In their new study, the findings of which now appear in the International Journal of Epidemiology, the investigators used a method called “Mendelian randomization.”

Mendelian randomizationTrusted Source allows researchers to look at genetic variations to assess causal relationships between various potential risk factors and the development of certain outcomes — in this case, prostate cancer.

Physical activity may more than halve risk

In their study, the researchers identified potential risk factors for prostate cancer through the World Cancer Research Fund’s (WCRF) 2018 systematic review of the evidence.

They also had access to the medical information of 79,148 participants with prostate cancer, as well as 61,106 participants without cancer who acted as the controls.

The analysis revealed that individuals with a genetic variation that increased their likelihood of being physically active had a 51% lower risk of prostate cancer than people who did not have this genetic variation.

Moreover, the researchers explain that “physical activity,” in this case, refers to all forms of activity, not just exercise.

Following on from this, the study authors conclude that interventions encouraging males to ramp up their levels of physical activity may have a protective effect against this widespread form of cancer.

“This study is the largest-ever of its kind, which uses a relatively new method that complements current observational research to discover what causes prostate cancer,” notes study co-author Sarah Lewis, Ph.D.

It suggests that there could be a larger effect of physical activity on prostate cancer than previously thought, so will hopefully encourage men to be more active.”

Sarah Lewis, Ph.D.

Anna Diaz Font, who is head of research funding at WCRF — which, alongside Cancer Research U.K., funded this study — emphasizes the importance of the current findings.

“Up till now, there has only been limited evidence of an effect of physical activity on prostate cancer. This new study looked at the effect of 22 risk factors on prostate cancer, but the results for physical activity were the most striking,” she says.

The study’s findings, Diaz Font believes, “will pave the way for even more research, where similar methods could be applied to other lifestyle factors, to help identify ways men can reduce their risk of prostate cancer.”

MedicalNewsToday

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