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Genetics of Prostate Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Introduction

Table 1. Relative Risk (RR) Related to Family History of Prostate Cancera continued...

Other potential modifiers of prostate cancer risk

Endogenous hormones, including both androgens and estrogens, likely influence prostate carcinogenesis. It has been widely reported that eunuchs and other individuals with castrate levels of testosterone prior to puberty do not develop prostate cancer.[37] Some investigators have considered the potential role of genetic variation in androgen biosynthesis and metabolism in prostate cancer risk,[38] including the potential role of the androgen receptor (AR) CAG repeat length in exon 1. This modulates AR activity, which may influence prostate cancer risk.[39] For example, a meta-analysis reported that AR CAG repeat length greater than or equal to 20 repeats conferred a protective effect for prostate cancer in subsets of men.[40]

Some dietary risk factors may be important modulators of prostate cancer risk; these include fat and/or meat consumption,[41] lycopene,[42,43] and dairy products/calcium/vitamin D.[44] Phytochemicals are plant-derived nonnutritive compounds, and it has been proposed that dietary phytoestrogens may play a role in prostate cancer prevention.[45] For example, Southeast Asian men typically consume soy products that contain a significant amount of phytoestrogens; this diet may contribute to the low risk of prostate cancer in the Asian population. There is little evidence that alcohol consumption is associated with the risk of developing prostate cancer; however, data suggest that smoking increases the risk of fatal prostate cancer.[46] Several studies have suggested that vasectomy increases the risk of prostate cancer,[47] but other studies have not confirmed this observation.[48] Obesity has also been associated with increased risk of advanced stage at diagnosis, prostate cancer metastases, and prostate cancer-specific death.[49,50]

Other nutrients have been studied for their potential influence on prostate cancer risk. The effect of selenium and vitamin E in preventing prostate cancer was studied in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). This randomized placebo-controlled trial of selenium and vitamin E among 35,533 healthy men found no evidence of a reduction in prostate cancer risk,[51] although a statistically significant increase (HR, 1.17; 99% CI, 1.004-1.36; P = .008) in prostate cancer with vitamin E supplementation alone was observed.[52] The absolute increased risk associated with vitamin E supplementation compared to placebo after more than 7 years of follow-up was 1.6 per 1,000 person years.

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