La era de la genética

 Alrededor de finales del siglo pasado se habia comenzado a hablar ya no de la medicina preventiva, sino de la medicina predictiva, a partir de obtener nuestra propia secuencia genética. Una idea que por entonces me resutaba novedosa y aún tan impactante como las posibilidades de la propia internet ( justo en la época que caía por primera vez la burbuja informática de Sillicon Valley ), los blogs existian, pero no con la facilidad de escribirlos como en este tiempo, y Google recién comenzaba a hacerse conocido ). Los tiempos cambian, y también, siempre que haya cierta cuota de honestidad intelectual, para consigo mismo primero, nos llevó a pensar en el determinismo genético y su verdadero rol en esta historia de la medicina predictiva. La propia genética, no tiene de por sí una historia tan pura, de la cual el propio nazismo puede dar cuentas. Ni tampoco se trata de una tecnologia tan nueva, ya que desde el comienzo de la historia, la propia humanidad experimentó con alimentos y aún con animales. Muchos de los alimentos que hoy conocemos como tal ( el maiz por dar un ejemplo), no eran asi unos 8 mil años atrás, y seguramente no lo serán en el futuro, pero esta vez gracias a Monsanto. En todo caso, el único mérito de Mendel, fue exponerlo como una disciplina que podia ser pausible de ser cientifica. Aunque las enfermedades y nuestra salud, sean en muy pocas ocasiones determinadas por nuestros genes ( como en el caso de las llamadas "enfermedades raras" ) , tan raras como los propios medicamentos que se les quiere imponer, o la medicalización personalizada a traves de anticuerpos monoclonales   En definitiva, mejor leamos la opinión del Equipo Cesca y seguimos pensandoló.

En el año 2000 comenzó en salud pública la era de la genética, que dejó atrás la era de los factores de riesgo. Pero en genética el avance sigue siendo más teórico que real como demuestran las respuestas terapéuticas a problemas concretos como las mutaciones de los genes BRCA y de la hemocromatosis (respectivamente, la mutilación pectoral y las sangrías mensuales). En este texto se analizan a fondo estos dos ejemplos.

• Estamos en la era de la genética, pero aplicamos remedios medievales (sobre los genes BRCA, la hemocromatosis y demás). Gérvas J. Bulletí Mèdic (Col.legi Oficial Metges Lleida). 2013; 103: 16-19. Descargar artículo completo aquí.

Survival in the Prostate Cancer Prevention Trial

To the Editor:

In their article on long-term survival in the Prostate Cancer Prevention Trial (PCPT), Thompson et al. (Aug. 15 issue)1 comment on the aggressiveness of high-grade disease (which they defined as a tumor having a Gleason score of 7 to 10). These authors have always argued that the increase in high-grade disease in men receiving finasteride was an artifact.2 If this were true, men with high-grade disease who are treated with finasteride should have a better survival rate than men in the placebo group. However, the survival rates in these groups were virtually the same. This finding indicates that the increase in high-grade disease is not an artifact but is real. The Food and Drug Administration rejected the use of finasteride for the prevention of prostate cancer on the basis of a related increase in the most aggressive, potentially lethal form of high-grade disease (Gleason score, 8 to 10), excluding the less aggressive pattern of disease (Gleason score of 7).3,4 In another recent report, the PCPT investigators stated that tumors with a Gleason score of 8 to 10 may cause “a small increase in prostate cancer mortality.”5 In the study published in the Journal, which defined a high-grade tumor as one having a Gleason score of 7 to 10, there is no report on prevalence or mortality for cancers with Gleason scores of 8 to 10. What are they?

Patrick C. Walsh, M.D.
Johns Hopkins Medical Institutions, Baltimore, MD
pwalsh@jhmi.edu

No potential conflict of interest relevant to this letter was reported.
5 References

To the Editor:

The 5-α reductase inhibitor finasteride has found considerable clinical use, not only in the treatment of prostate disease but also as a treatment for male-pattern alopecia. Concerns have been raised about the potential for an increased risk of male breast cancer among patients receiving finasteride.1,2 Given that the PCPT involved a very large sample of more than 18,000 men, the investigators have the opportunity to study the incidence patterns of male breast cancer among the patients enrolled in the trial.

Swaroop Revannasiddaiah, M.D.
Swami Rama Cancer Hospital and Research Institute, Haldwani, India
swarooptheone@gmail.com
Sridhar P. Susheela, M.D.
Bangalore Institute of Oncology, Bengaluru, India

No potential conflict of interest relevant to this letter was reported.
2 References

The authors reply: In response to Walsh: the outcomes according to Gleason score in our recent report, with scores of 2 to 6 indicating low-grade tumors and scores of 7 to 10 indicating high-grade tumors, were consistent with those in our initial 2003 report.1 Table 1Table 1Estimates of Postdiagnostic Survival for Men with Tumors with Gleason Scores of 8 to 10 in the Prostate Cancer Prevention Trial. shows postdiagnostic Kaplan–Meier survival estimates for patients with Gleason scores between 8 and 10. In this small subset of men from the PCPT, confidence intervals are wide and overlap. Modeling the time from randomization to death with the use of time-dependent covariates to account for the time at which the diagnosis of prostate cancer occurred (an approach that is less biased than one incorporating postdiagnostic survival), we calculated the between-group difference in the hazard ratios for death when Gleason scores of 8 to 10 rather than 7 to 10 were used to indicate high-grade cancer. After adjusting for age and race, we found that the P value for the comparison was 0.59, indicating that there was no statistically significant difference in survival. However, this test is also underpowered and represents another reason why we chose not to highlight this subset in our article.
Revannasiddaiah and Susheela ask about the incidence of male breast cancer in the PCPT trial. With 141,009 person-years of follow-up, there have been two cases, one in each of the two study groups.

Catherine M. Tangen, Dr.P.H.
Phyllis J. Goodman, M.S.
Fred Hutchinson Cancer Research Center, Seattle, WA
Ian M. Thompson, Jr., M.D.
Cancer Therapy and Research Center, San Antonio, TX
thompsoni@uthscsa.edu

Since publication of their article, the authors report no further potential conflict of interest.
1 Reference

Related Article
 

Long-Term Survival of Participants in the Prostate Cancer Prevention Trial

August 15, 2013 | I.M. Thompson and Others

NICE: Guidance on familial breast cancer.

Ovarian and breast cancer patients in a pedigree chart of a family (Photo credit: Wikipedia)

Familial breast cancer occurs in people with one or more family members affected by breast, ovarian, or a related cancer such as primary peritoneal cancer. About 5% of all breast cancers can be attributed to inherited mutations in specific high risk genes such as BRCA1, BRCA2, and TP53.

This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the classification and care of people at risk of familial breast cancer.1 The guideline updates previous NICE guidance on familial breast cancer, published in 2004 and 2006.2 3 It also provides new guidance on men and women with a newly or previously diagnosed breast cancer who have a family history of breast and ovarian cancer, as they were excluded from previous guidance.4

Full Text from NICE

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Study Reports a 12.3% Rate of Bladder Cancer Mortality at 10 Years for Patients With High-Risk Bladder Cancer

Age-standardised death rates from Malignant neoplasms by country (per 100,000 inhabitants). (Photo credit: Wikipedia)

Cancer 2013 Jun 04;[EPub Ahead of Print], K Chamie, MS Litwin, JC Bassett, TJ Daskivich, J Lai, JM Hanley, BR Konety, CS Saigal

TAKE-HOME MESSAGE

An examination of outcome for over 7000 patients with high-grade non-muscle invasive bladder cancer reports a 12.3% rate of bladder cancer mortality at 10 years.

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ABSTRACT
Background: Patients with bladder cancer are apt to develop multiple recurrences that require intervention. The recurrence, progression, and bladder cancer-related mortality rates were examined in a cohort of individuals with high-grade non-muscle-invasive bladder cancer.
Methods: Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, subjects were identified who had a diagnosis of high-grade, non-muscle-invasive disease in 1992 to 2002 and who were followed until 2007. Multivariate competing-risks regression analyses were then used to examine recurrence, progression, and bladder cancer-related mortality rates.
Results: Of 7410 subjects, 2897 (39.1%) experienced a recurrence without progression, 2449 (33.0%) experienced disease progression, of whom 981 succumbed to bladder cancer. Using competing-risks regression analysis, the 10-year recurrence, progression, and bladder cancer-related mortality rates were found to be 74.3%, 33.3%, and 12.3%, respectively. Stage T1 was the only variable associated with a higher rate of recurrence. Women, black race, undifferentiated grade, and stage Tis and T1 were associated with a higher risk of progression and mortality. Advanced age (≥ 70) was associated with a higher risk of bladder cancer-related mortality.
Conclusions: Nearly three-fourths of patients diagnosed with high-risk bladder cancer will recur, progress, or die within 10 years of their diagnosis. Even though most patients do not die of bladder cancer, the vast majority endures the morbidity of recurrence and progression of their cancer. Increasing efforts should be made to offer patients intravesical therapy with the goal of minimizing the incidence of recurrences. Furthermore, the high recurrence rate seen during the first 2 years of diagnosis warrants an intense surveillance schedule.

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Cancer

Recurrence of High-Risk Bladder Cancer: A Population-Based Analysis

Cancer 2013 Jun 04;[EPub Ahead of Print], K Chamie, MS Litwin, JC Bassett, TJ Daskivich, J Lai, JM Hanley, BR Konety, CS Saigal

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Influence of Study Features and Methods on Overdiagnosis Estimates in Breast and Prostate Cancer Screening

Ruth Etzioni, PhD; Roman Gulati, MS; Leslie Mallinger, MPH; and Jeanne Mandelblatt, MD, MPH

Source: Ann Intern Med. 2013;158(11):831-838. doi:10.7326/0003-4819-158-11-201306040-00008

Knowledge of the likelihood that a screening-detected case of cancer has been overdiagnosed is vitally important to make treatment decisions and develop screening policy. An overdiagnosed case is an excess case detected by screening. Estimates of the frequency of overdiagnosis in breast and prostate cancer screening vary greatly across studies. This article identifies features of overdiagnosis studies that influence results and shows their effect by using published research. First, different ways to define and measure overdiagnosis are considered. Second, contextual features and how they affect overdiagnosis estimates are examined. Third, the effect of estimation approach is discussed. Many studies use excess incidence under screening as a proxy for overdiagnosis. Others use statistical models to make inferences about lead time or natural history and then derive the corresponding fraction of cases that are overdiagnosed. This article concludes with questions that readers of overdiagnosis studies can use to evaluate the validity and relevance of published estimates and recommends that authors of studies quantifying overdiagnosis provide information about these features.

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Cancer in children and teenagers linked with CT scan

English: Ct-scan of the brain with hydrocephalus Nederlands: Ct-scan van de hersenen met hydrocefalus (Photo credit: Wikipedia)

 Full Text


The long-term risk of cancer is about one-fourth higher for children and adolescents exposure to computed tomography (CT) scanning, reports a study in the June 1, 2013, British Medical Journal.

Using Australian Medicare data from 1985 through 2005, the researchers identified 10.9 million children and adolescents (aged 0 to 19 years) who underwent CT scans during this time. Subsequent cancer diagnoses through 2007 were identified by linkage to national cancer data.

The incidence of cancer among children and adolescents exposed to CT scans more than 1 year before any cancer diagnosis was assessed, compared to nonexposed individuals. The lead author was John D. Mathews of University of Melbourne.

A total of 60,674 cancers were identified in the study cohort. Of these, 3,150 cancers occurred in young people with exposure to CT scanning at least 1 year before cancer diagnosis.

After adjustment for age, sex, and year of birth, overall cancer incidence was significantly higher for children and adolescents exposed to CT scanning: incidence rate ratio (IRR) 1.24. There was evidence of a dose-response effect, with IRR increasing by 0.16 per additional CT scan.

Cancer risk associated with CT scans increased with time since exposure: IRR 1.3 for 1 to 4 years, 1.25 for 5 to 9 years, 1.14 for 10 to 14 years, and 1.24 for 15 years or longer. The increase in risk was significant for many types of solid cancers as well as for leukemia, myelodysplasia, and certain other lymphoid cancers.

A total of 608 excess cancers occurred among CT-exposed young people, including 147 brain cancers, 356 other solid tumors, 48 cases of leukemia or myelodysplasia, and 57 other lymphoid cancers. Through 2007, the absolute excess incidence was 9.38 per 100,000 person-years at risk. The average effective radiation dose per CT scan was estimated at 4.5 mSv.

The increased use of CT scanning raises concerns about long-term cancer risk, particular in children. The new study demonstrates an increased incidence of cancer among children and adolescents exposed to CT scans between 1985 and 2005. The excess risk is "mostly due to irradiation," the researchers write.

Longer follow-up will be needed to determine the ultimate lifetime risk. The investigators conclude, "Future CT scans should be limited to situations where there is a definite clinical indication, with every scan optimised to provide a diagnostic CT image at the lowest possible radiation dose."

Objective To assess the cancer risk in children and adolescents following exposure to low dose ionising radiation from diagnostic computed tomography (CT) scans.

Design Population based, cohort, data linkage study in Australia.

Cohort members 10.9 million people identified from Australian Medicare records, aged 0-19 years on 1 January 1985 or born between 1 January 1985 and 31 December 2005; all exposures to CT scans funded by Medicare during 1985-2005 were identified for this cohort. Cancers diagnosed in cohort members up to 31 December 2007 were obtained through linkage to national cancer records.

Main outcome Cancer incidence rates in individuals exposed to a CT scan more than one year before any cancer diagnosis, compared with cancer incidence rates in unexposed individuals.

Results 60 674 cancers were recorded, including 3150 in 680 211 people exposed to a CT scan at least one year before any cancer diagnosis. The mean duration of follow-up after exposure was 9.5 years. Overall cancer incidence was 24% greater for exposed than for unexposed people, after accounting for age, sex, and year of birth (incidence rate ratio (IRR) 1.24 (95% confidence interval 1.20 to 1.29); P<0 .001="" 0.16="" 0.19="" 1-4="" 1.14="" 1.22="" 1.24="" 1.25="" 1.34="" 1.35="" 1.45="" 10-14="" 15="" 5-9="" a="" additional="" after="" ages="" and="" at="" by="" class="zem_slink" ct="" dose-response="" each="" exposure="" first="" for="" greater="" href="http://en.wikipedia.org/wiki/Cancer" increased="" irr="" irrs="" many="" more="" of="" or="" rel="wikipedia" relation="" respectively.="" saw="" scan.="" significantly="" since="" target="_blank" the="" title="Cancer" to="" trend="" types="" was="" we="" were="" years="" younger="">solid cancer

(digestive organs, melanoma, soft tissue, female genital, urinary tract, brain, and thyroid); leukaemia, myelodysplasia, and some other lymphoid cancers. There was an excess of 608 cancers in people exposed to CT scans (147 brain, 356 other solid, 48 leukaemia or myelodysplasia, and 57 other lymphoid). The absolute excess incidence rate for all cancers combined was 9.38 per 100 000 person years at risk, as of 31 December 2007. The average effective radiation dose per scan was estimated as 4.5 mSv.

Conclusions The increased incidence of cancer after CT scan exposure in this cohort was mostly due to irradiation. Because the cancer excess was still continuing at the end of follow-up, the eventual lifetime risk from CT scans cannot yet be determined. Radiation doses from contemporary CT scans are likely to be lower than those in 1985-2005, but some increase in cancer risk is still likely from current scans. Future CT scans should be limited to situations where there is a definite clinical indication, with every scan optimised to provide a diagnostic CT image at the lowest possible radiation dose.

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Insulina Glargina y cancer

Desde Hemos Leido y sin anestesia:


 
Han tenido que pasar cuatro años para despejar las dudas sobre una posible asociación entre el uso de la insulina glargina y el desarrollo de cáncer, ya que, en junio de 2009, tanto la EMEA como la AEMPS emitieron comunicados informando que la bibliografía disponible en ese momento era insuficiente para adoptar medidas reguladoras o recomendar un cambio de tratamiento de los pacientes que utilizan insulina glargina.
 
Esta recomendación tuvo que ser realizada por la alarma surgida tras la publicación en la revista Diabetología, de datos procedentes de cuatro estudios observacionales sobre la posible asociación entre el uso de la insulina glargina y el desarrollo de cáncer, especialmente cáncer de mama.
 
Desde entonces, el CHMP de la EMA solicitó a la empresa que comercializa el medicamento que proporcionara más datos.
 
¿Qué datos se incluyeron en esta revisión de la EMA?
 
La presente revisión incluye datos de tres estudios poblacionales. Dos de ellos fueron estudios de cohortes:
 
         * uno basado en los datos recogidos de alrededor de 175.000 pacientes en el norte de Europa que fueron tratados con insulina glargina, insulina humana o insulina combinada,
 
         * otro con datos de alrededor de 140.000 pacientes en los Estados Unidos.
 
Ambos estudios analizaron la incidencia de cáncer de mama, colorrectal y de próstata con las diferentes insulinas.
 
El tercer estudio fue un estudio “caso-control” llevado a cabo en Canadá, Francia y el Reino Unido. Este estudio comparó 775 pacientes con diabetes que padecía cáncer de mama con un grupo control de pacientes con diabetes que no tenían cáncer de mama. El objetivo era establecer si existía alguna relación entre las insulinas que los pacientes estaban recibiendo y la aparición de cáncer de mama. Este estudio comparó la insulina glargina con insulina humana y otros tipos de insulina.
 
La revisión también incluyó datos obtenidos de una búsqueda exhaustiva de estudios en la literatura científica la investigación de la relación entre la insulina glargina y el cáncer.
 
Basándose en la evaluación de estos estudios, el CHMP ha concluido que, en general, los datos NO indican un aumento del riesgo de cáncer con insulina glargina, señalando que no existe un mecanismo conocido por el que la insulina glargina pudiera causar cáncer y que el riesgo de cáncer no se ha visto en estudios de laboratorio.
 
No obstante, la EMA continuará evaluando nuevos datos que están disponibles en esta área, como parte de la vigilancia rutinaria de los medicamentos.
 
(NOTA DE “HEMOS LEÍDO”: No hemos podido enlazar los estudios mencionados a sus lugares de publicación porque la nota de la EMA no contiene bibliografía).

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