Nutrigenetics and Prostate Cancer: 2011 and Beyond

Abstract

Background/Aims: Prostate cancer runs in families and shows a clear dietary involvement. Until recently, the key risk gene(s) have proved elusive. We summarise current understandings of nutrient-gene interactions in prostate cancer risk and progression. Methods: A MEDLINE-based literature search was conducted. Results: Hypothesis-directed candidate gene approaches provide plausible, albeit statistically weak, nutrient-gene interactions. These are based on early understandings of factors likely to impact on carcinogenesis, including both nutrient and genetic effects on androgen biosynthesis and action, xenobiotic metabolism, DNA damage and DNA repair. Non-hypothesis-directed genome-wide association studies provide much stronger evidence for other genes, not hitherto suspected for involvement. Although only a few of these have been formally tested for dietary associations in well-designed epidemiologic studies, the nature of many of the genes suggests that their activity may be regulated by nutrients. These effects may not only be relevant to prostate cancer susceptibility, but also to disease progression. Conclusions: It will be important to move beyond studying single nucleotide polymorphisms, into more complex chromosomal rearrangements and to epigenetic changes. For future progress, large international cohorts will not only need to provide proof of individual nutrient-gene interactions, but also to relate these to more complex nutrient-gene-gene interactions, as parts of pathways. Bioinformatics and biostatistics will be increasingly important tools in nutrigenetic studies beyond 2011.

Association between the 8473T>C Polymorphism of <b><i>PTGS2</i></b> and Prostate Cancer Risk: A Metaanalysis Including 24,716 Subjects

“…The development of PCa is a complicated multistage process with multiple genes and factors. Nutrient-gene interactions existed in PCa progression [35]. Diet and environment have been recognized as important factors [35,36,37,38,39,40,41,42].…”

Environmentally induced epigenetic transgenerational inheritance of phenotype and disease

“…Examples of such observations follow:

The association of disease states with single nucleotide polymorphisms (SNPs) in the “Genome-Wide Association Studies” (GWAS) has revealed that genetic components usually explain less than 20% of the phenotypic variance (Wallace, 2010). The importance of moving beyond studying SNPs to examine more complex chromosomal regulation and epigenetic changes is paramount (Yuan and Ferguson, 2011).

The premise that a detailed genetic knowledge would allow the causes of the majority of diseases to be determined, which was based on a reductionist view of genotype–phenotype correlations, is now proven to be false when the evidence suggests that the majority of diseases are complex traits (Dipple et al, 2001).

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“…The importance of moving beyond studying SNPs to examine more complex chromosomal regulation and epigenetic changes is paramount (Yuan and Ferguson, 2011). …”

Anti‐proliferative effects of physiological concentrations of enterolactone in models of prostate tumourigenesis

“…Prostate cancer is the second most frequently diagnosed cancer in the world and the most common cancer in men . Despite its high morbidity, the aetiology of prostate cancer remains unknown with the only established risk factors being advancing age, ethnic origin, and heredity . There are considerable geographical differences in the incidence of the disease, which is much higher in Western or Westernised societies compared to Eastern societies .…”

“…raised in different environments show a similar risk of developing the disease to those in their country of residency, suggesting that environmental factors may be important in the risk and development of the disease [4,5]. Geographical differences in diet and prostate disease risk are thought to be important, but a clear link remains elusive [3,7,8,[12][13][14][15][16][17][18][19]. This is due, in part, to a lack of understanding of the effects, or absence of effects, of specific foods and nutrients on prostate tumourigenesis.…”