Study: The effect of finasteride on prostate cancer

Reference

Brasky TM, Till C, White e, et al. Serum phospholipid fatty acids and prostate cancer risk: results of the prostate cancer prevention study. am j epidem. 2011. April 24

Design

A 7-year-old, randomized, placebo-controlled study in which it was tested whether the 5-alpha reductase inhibitor finasteride lowers the risk of prostate cancer (PCA). In the course of the study, the men were tested annually for the prostate -specific antigen (PSA) and the digital rectal examination (DRE). Men with an abnormal DRE or PSA value>/= 4.0 ng/ml was recommended for a prostate tabiopsia. At the end of the study, all men in whom no PCA had been diagnosed were asked to undergo prostate tabiopsia.

A case control study was carried out as part of the prostate cancer prevention study. The serum phospholipid levels were compared by 1,809 men with invasive prostate cancer and 1,809 men (controls) confirmed by biopsy who were free of disease in the biopsy at the end of the study. The frequency of the controls was adapted to cases based on the age distribution (+/- 5 years), the treatment group (finasteride/placebo) and a first degree relative to PCA.

participant

18,882 men aged 55 or older were randomized and received finasteride or placebo.

study medication

The test subjects received 5 mg finasteride/day.

target parameter

serum samples were collected and pooled in the 1st and 4th year to reduce the intra-individual variability of the phospholipid fatty acid assay. Calculations for eicosapentaenic acid (EPA) + Docsahexaenoic acid (DHA) were carried out as a measure of all long-chain omega-02 fatty acids; Linol and arachidonic acid as a measure of the entire omega-6 fatty acids; Overall trans fatty acids (TFA) 18: 1; Total Tfa 16; and overall Tfa 18: 2.

The primary result of the result was the distribution of serum phospholipid fatty acids as a percentage of the total amount of PCA cases and control persons, stratified according to prostate cancer degree.

most important knowledge

The DHA values ​​were higher in high grade cases than in the controls. The TFA values ​​18: 1 and 18: 2 were significantly lower in high-grade cases compared to the controls. There were no further significant differences in the remaining phospholipids between the control and the cancer group. EPA was not associated with the risk of high -grade PCA, and the associations were similar to EPA+DHA.

effects on practice

epidemiological, animal model and in-vitro studies indicate that omega-3 fatty acids, lycopine and selenium have a chemical-preventive effect on PCA. ¹ The results of this study contradict the researchers' hypothesis that omega-6 and Tfas reverses with which PCA risk would be associated. Although unexpectedly, the authors cite several other studies that match their results, and there is a possibility that there is a reverse connection between fish consumption and advanced or fatal prostate cancer. However, it is important to consider that an increased PCA risk was only found in DHA and only with high-grade prostate cancer. Before conclusive recommendations can be made, a repetition in further studies is required.

A significant restriction of this seroepidemiological study is based on the fact that fatal prostate cancer lasts many years from the creation to death. The question is whether the fatty acid content in the blood of a man is a reliable measure of its average fatty acid status over two days of thousands of days in these years. Another restriction is that the researchers have not taken into account the effects of vitamin E, selenium, lycopine, cross -flowers, meat and dairy products.

It is assumed that EPA and DHA generally reduce the risk of cancer through their anti -inflammatory and immunomodulatory properties as well as the impairment of cell permeability, gene expression and signal transduction. The effects of omega-3 fatty acids on these paths in prostate cancer are not fully clarified. There is no known mechanism through which EPA or DHA could work, nor are there any indications of cancer -inhibiting properties of trans fats.

genetic and molecular studies on high -grade intraepithelial neoplasia of the prostate have shown that the focus is on the loss of heterocygoty and that certain oncogenes are expressed. ^{2 What causes the expression of these oncogenes? What does your expression regulate?}

androgenic hormones are necessary for the growth and development of the prostate. It is not surprising that polymorphic variants of genes that are involved in the androgen effect can influence the PCA risk. African Americans who have a higher PCA risk than Asians have androgen receptor polymorphisms that lead to an increased predisposition. 5-alpha reductase variants can also react differently to the inhibition through finasteride.

The most important lifestyle factor in the United States, which is most likely responsible for a high PCA incidence, is the diet that is generally rich in animal fats and meat and arm of fruit and vegetables.

collected epidemiological findings indicate that the environment is the main cause of the development of most prostate cancer. The PCA incidence has great geographical differences, with high rates in the USA and Western Europe and low rates in Asia. African Americans have a very high risk of PCA. The geographical differences can best be explained by the lifestyle, since Asian immigrants to North America are exposed to a higher PCA risk. The most important lifestyle factor in the United States, which is most likely responsible for high PCA incidence, is the diet that is generally rich in animal fats and meat and arm of fruit and vegetables. The total fat absorption, the absorption of animal fats and the consumption of red meat are associated with an increased PCA risk. ^{3 The use of 2-amino-1-methyl-6-phenylimidazopyridine, one of the Hererocyclic Amine, which occurs in "fried" red meat, leads to rats PCA. 4 The consumption of dairy products increases the PCA risk. 5}

The consumption of lycopine, cross-flowers, vitamin E and selenium reduces the PCA risk. ^{6,7,8
The role of genetics in the identification of people with high risk of prostate cancer is still in its infancy, but epidemiological studies support the concept that plays a role and clinical studies The observation that prostate cancer is very aggressive in some people in the early stages, while the majority are sluggish. By linking these two factors, a population of men should be identified in which screening, early detection and chemo prevention can be used intensively. In the meantime, the main author expressed the message of this study to take away: "Overall, the positive effects of eating fish to prevent heart diseases outweigh all damage in connection with the risk of prostate cancer."}

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