Role of Hormonal and Other Factors in Human Prostate Cancer

Abstract

American men have a lifetime risk of about 18% for prostate cancer diagnosis. Large international variations in prostate cancer risks and increased risks among migrants from low- to high-risk countries indicate important roles for environmental factors. Major known risk factors include age, family history, and country/ethnicity. Type 2 diabetes appears to reduce risk, while high birth weight and adult height are linked to increased risk of aggressive prostate cancer. Limited evidence supports an association with a history of sexually transmitted infections. A previous meta-analysis of eight cohort studies indicated no associations with plasma androgen, estrogen, or sex hormone binding globulin (SHBG) levels. However, there were dose-response relationships with baseline plasma testosterone levels in two studies that adjusted for other serum hormones and obesity. Finasteride (a drug that blocks testosterone activation) reduced prostate cancer risk by 25%. Low-frequency genes linked to familial prostate cancer only explain a small fraction of all cases. Sporadic cases were linked to relatively common polymorphisms of genes involved in (1) androgen synthesis, activation, inactivation and excretion, (2) hormone and vitamin D receptors, (3) carcinogen metabolism, and (4) DNA repair. Epidemiologic evidence supports protective roles for dietary selenium, vitamin E, pulses, tomatoes/lycopene, and soy foods, and high plasma 1,25-dihydroxyvitamin D levels. There is inadequate evidence that vegetables, fruit, carotenoids, and vitamins A and C reduce risk and that animal fat, alpha-linoleic acid, meat, coffee, and tea increase risk. Two major cohort studies found dose-response relationships with dietary calcium intake. Total dietary energy intake may enhance risk. Limited evidence supports a protective role for physical activity and elevated risk for farmers and other men with occupational pesticide exposure, particularly to organochlorine compounds and phenoxy herbicides. There is inadequate evidence for a relationship with alcohol or smoking. Most known or suspected external risk factors may act through hormonal mechanisms, but our review found little supporting evidence, and substantial further research is needed.

Factores de riesgo constitucionales en el cáncer de próstata

“…Los andrógenos influyen en el desarrollo, maduración y crecimiento de la próstata y afectan tanto a la proliferación como a la diferenciación de su epitelio 7,[14][15][16][17][18] . La testosterona, principal andrógeno circulante, y la dihidrotestosterona, principal andrógeno tisular, son los dos más importantes.…”

“…Numerosos estudios prospectivos han investigado el papel de los andrógenos plasmáticos sobre el cáncer de próstata, pero muy pocos han demostrado que los hombres con niveles séricos elevados de andrógenos tengan mayor riesgo de desarrollar la enfermedad. En el Physician's Health Study Cohort 16 se observó mayor riesgo con niveles elevados de testosterona y bajos de globulina trasportadora de hormonas sexuales (SHBG), aunque un metaanálisis posterior de 8 estudios de cohortes, y otros estudios, 14,18 han demostrado que no había ninguna relación entre el desarrollo del cáncer de próstata y niveles plasmáticos de testosterona, dihidrotestosterona, androstenodiona o sulfato de dihidroepiandosterona. Uno de los estudios más importantes sobre la influencia androgénica en el desarrollo del cáncer prostá-tico lo constituye el Prostate Cancer Preventive Trial 17 , que aleatorizó a 18.000 hombres a recibir placebo o finasterida (inhibidor de la 5 ␣ reductasa isoenzima tipo 2) durante 7 años.…”

“…Aunque algunos autores han encontrado una relación inversa entre los niveles de la hormona sexual ligada a la globulina y el riesgo de desarrollar la enfermedad, la mayor parte de estudios no encuentra esta asociación 5,14 . También parece que la insulina actúa como factor hormonal de crecimiento, regulando la proliferación, diferenciación y apoptosis celular.…”

Natural Hormones in Food-Producing Animals:Legal Measurements and Analytical Implications

“…On the other hand, a tendency to increasing incidence of certain cancer types, such as testicle, breast and prostate cancer, has not been fully clarified yet, though sex hormones are suspected to play a key role (Foster et al, 2008;Huyghe et al, 2003;Prins, 2008;Wigle et al, 2008). For instance lung cancer, which is the leading cause of cancer deaths in the United States and has surpassed breast cancer as the primary cause of cancer-related mortality in women, has been related to estradiol along with tobacco consumption by Meireles et al (Meireles et al, 2010).…”

Prostate Cancer

“…Lower blood levels of vitamin D may increase the risk of developing prostate cancer 15 . Folic acid supplements have no effect on the risk of developing prostate cancer 16 . The role of High fatty Diet(HFD) is discussed in later part under separate heading.…”