Relation between the selenoprotein gene, selenium, and prostate cancer.

摘要

Prostate cancer is a complex: disease and substantial efforts have been devoted to determine its causes. Very few unequivocal risk factors are known for prostate cancer, even though it is the most common cancer among men after skin malignancies. Aging, family history, and ethnicity increase the risk of developing prostate cancer. Family history and ethnicity suggest a genetic cause. However, migration studies have shown the incidence rates for first- and second-generation individuals from a country with a low prostate cancer incidence rate will approach the host country's incidence rate, supporting the existence of environmental factors. Hence, prostate cancer might be due to the independent and interacting effects of genes and environmental factors. Here we investigate the potential effects of a novel selenoprotein gene, Sep15, and selenium intake on prostate cancer and aggressiveness. We use two different study designs: sibling- and hospital-based, allowing for potential replication of the findings. Sep15 is a recently identified selenoprotein highly expressed in prostate tissue. Two single nucleotide polymorphisms, one of which appears to be functional, have been identified within the gene, and are evaluated here. Selenium intake was measured using a food frequency and a vitamin/supplement questionnaire. The independent effects of each variable, the Sep15 variants and selenium intake, will be evaluated within the two studies using appropriate statistical methods. Caucasians in the sibling-based study with low grade prostate cancer had an increased risk of disease (OR=4.04: 95%CI: 1.63--10.01). In the same study, Caucasians were protected from aggressive prostate cancer (OR=0.10; 95%CI: 0.03--0.36). A contrast existed between study designs for selenium supplement use. A protective effect for selenium supplements was seen in the hospital-based study (OR=0.61; 95%CI: 0.46--0.80), while an increased risk was seen in the sibling-based study (OR=1.23; 95%CI: 0.99--1.54). The inconsistent results may be due to the presence of prevalent cases in the sibling-based study and dietary measurement error. Sample size for the two studies restricted the assessment for an interaction between Sep15 and selenium. The Sep15 gene appears to have an impact on prostate cancer aggressiveness and initiation.