Gene polymorphisms and prostate cancer: the evidence

Abstract

OBJECTIVE Prostate cancer is still the most frequent noncutaneous male malignancy and is the second most common cause of cancer death. Genetic factors have been extensively studied in different countries. In addition, numerous genome–wide association studies have been performed in developed countries. Genetic tests will be applied in the near future for diagnosis, therapeutic, and prognostic significance. Therefore, we reviewed the association of several important pathways and genes with critical functions in prostate cancer development or progression. MATERIALS AND METHODS We performed a PubMed® search using several key words such as prostate cancer, names of important genes with critical function, and polymorphisms. Then, we reviewed retrieved articles as well as relevant articles from 1997 to 2009. RESULTS There are conflicting results of studies on some gene polymorphisms in association with prostate cancer. Most of the inconsistent results have been reported in studies investigating the vitamin D receptor gene polymorphism in association with prostate cancer. Genes related to angiogenesis and cell adhesion genes are more promising. Following results of future studies, the use of antibodies blocking over‐expressed genes or proteins may be supported in patients with prostate cancer. CONCLUSIONS The difference between the results of studies on gene polymorphisms in prostate cancer may be explained partly by ethnic differences, limited sample size, and other risk or protective factors modifying these effects. Genome‐wide studies are currently performed in developed countries and extensive use of this type of analysis may merit consideration in other countries. Furthermore, future studies are needed to further investigate environmental and diet factors interactions with genetic factors.

Genetic Association Studies on Prostate Cancer

“…Candidates were selected based on their potential functional significance in normal prostatic cell growth, malignant transformation, or in the development of metastases. Therefore, among these candidate genes are those encoding proteins involved in androgen signaling, cell-cycle control mechanisms, major tumor-suppressors, or proto-oncogenes, as well as those involved in cellular adhesion or communication with surrounding cellular or matrix components of prostate epithelium [62,63]. This implies the need for previous knowledge when designing case-control studies using candidate gene approach [64].…”

“…Also, genetic variants in genes involved in these processes could potentially attribute to cancer susceptibility and/or progression risk [62].…”

“…Also, the importance of vascular support to cancer growth stimulated the association studies on PCa analyzing genetic variants located in angiogenesis-related genes [62]. Since these processes are codependent, numerous genes primarily found to be involved in chronic inflammation are also discussed as angiogenesis-related genes, and vice versa.…”

Factores de riesgo constitucionales en el cáncer de próstata

“…Cuando algunas mutaciones están presentes en las células germinales se transmiten de generación en generación y están presentes en todas las células del organismo, incluyendo lógicamente las prostáticas. Esta última modalidad da lugar a los síndromes familiares de cáncer prostático, que constituyen entre el 13 y el 26% del total de estos tumores [9][10][11][12][13] . En la mayoría de estos síndromes las mutaciones son alélicas y de baja penetrancia, pero en el 5% las mutaciones son de alta penetrancia y se transmiten de forma autosómica dominante, siguiendo los patrones clásicos de la herencia mendeliana (tabla 2).…”

“…Por todo ello, algunos autores atribuyen hasta el 40% de todos los cánceres de próstata a factores genéticos. El mayor riesgo viene generado por la implicación de las vías metabólicas referidas en la tabla 3, que incrementan la transformación neoplásica de las células epiteliales prostáticas [10][11][12][13] .…”