Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium.
نویسندگان
چکیده
BACKGROUND Studies suggest that vitamin D status may be associated with prostate cancer risk although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D [25(OH)D] status. We examined prostate cancer risk in relation to single-nucleotide polymorphisms (SNP) in four genes shown to predict circulating levels of 25(OH)D. METHODS SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the National Cancer Institute (NCI) Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. RESULTS We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D [per A allele, OR, 0.86; 95% confidence interval (CI), 0.80-0.93; Ptrend = 0.0002) but an increased risk for nonaggressive disease (per A allele: OR, 1.10; 95% CI, 1.04-1.17; Ptrend = 0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles, 0.66; 95% CI, 0.44-0.98; Ptrend = 0.003). CONCLUSIONS In this large, pooled analysis, genetic variants related to lower 25(OH)D levels were associated with a decreased risk of aggressive prostate cancer. IMPACT Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk.
منابع مشابه
ژنتیک مولکولی، تشخیص، پیشگیری و ژن درمانی در سرطان پروستات: مقاله مروری
The prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer), and also the second leading cause of cancer death (after lung cancer) among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes....
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ورودعنوان ژورنال:
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
دوره 22 4 شماره
صفحات -
تاریخ انتشار 2013