Have questions? Visit https://www.reddit.com/r/SNPedia

Prostate cancer

From SNPedia

A recent (2015) review SNPs influencing prostate cancer risk or progression is here. For a relatively recent (2014) summary of 77 independent risk loci associated in GWAS studies with prostate cancer, listing one SNP per locus, see [PMID 24497837].

[PMID 17485362] Presents an exhaustive review of published research finding some - or no - association for various SNPs with prostate cancer, as of 2007.

A report that attracted some media attention (January 2008; 10.1056/NEJMoa075819) of a model for risk of prostate cancer was based on a combination of 5 SNPs plus family history, which the authors believe may account for 50% of the cancers. Although the model estimates risk, clinical parameters (such as age of onset and disease progression) are not predicted by this model. The 5 SNPs chosen to represent five regions of chromosomes 17q12, 17q24.3 and 8q24 (three regions) are:

More recent research would most likely define a haplotype on 8q24 (see rs138042437) as well as rs138213197, in the HOXB13 gene.

Risk for prostate cancer (shown here as odds ratio, with CI) increases cumulatively based on the number of SNP risk genotypes for these 5 (or, second set of numbers, with family history counted as a 6th factor) as follows:

0: 1.00
1: 1.50 (CI: 1.18-1.92); 1.62 (1.27-2.08)
2: 1.96 (1.54-2.49); 2.07 (1.62-2.64)
3: 2.21 (1.70-2.89); 2.71 (2.08-3.53)
4: 4.47 (2.93-6.80); 4.76 (3.31-6.84)
5: 4.47 (2.93-6.80); 9.46 (3.62-24.72)
6: 9.46 (3.62-24.72)

Based on the data in this study, family history on its own (in the absence of any SNP information) yields an odds ratio of 2.22 (CI: 1.83-2.68) and can account for ~10% of the population attributable risk for prostate cancer.10.1056/NEJMoa075819

Separate from the risk of developing prostate cancer is the risk to a (known) prostate cancer patient of actually dying from the disease (known as prostate cancer specific mortality, or PCSM). A set of 5 SNPs was reported in 2011 to offer some predictive significance with regard to PCSM, with hazard ratios of 1.25 and 1.5 for carriers of 3 and 4 (or 5) of the risk alleles, respectively. Carriers of these risk genotypes are identified by genosets gs242 and gs243.

One SNP has been found to be associated not only with prostate cancer in general, but also specifically with aggressive prostate cancer [PMID 18073375]:

Another SNP has been found to be related to the aggressive form (PMID pending):

This study [PMID 18073375] also reported 6 additional SNPs (in addition to rs1571801) found in common between the CAPS and CGEMS study groups:

There is evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with a variation of rs2987983 in the promoter region of the estrogen receptor-beta gene [PMID 16921512]

[1] Seven snps in 8q24 play a significant role in prostate cancer. [PMID 17401366, PMID 17401363]

[2] The rs1447295 location could be responsible for about seven percent of prostate cancer cases in white men of north European descent. Thus, taken together with rs6983267, these two genetic changes could account for as much as one quarter of prostate cancer cases in white men. The increased risk conferred by these loci was observed for all age groups studied.

[PMID 18264098] 38,000+ Icelandic, European and US individuals were analyzed to reveal association with prostate cancer and 2 SNPs: rs721048, in chr 2p15, and rs5945572, in ch Xp11.22.

[PMID 17932346]] Two SNPs within the VDR gene, rs2107301 and rs2238135, are associated with a 2.5x higher risk of prostate cancer

Faulty gene linked to PC risk

[PMID 17085659] Variants of the hK2 protein gene (KLK2) predict the presence of prostate cancer at biopsy

[PMID 14961571, PMID 16189707] rs16260 (A) variant in E-cadherin CDH1 gene is associated with increased risk of hereditary prostate cancer.

[PMID 17066444] Frequent consumption of fatty fish and marine fatty acids appears to reduce the risk of prostate cancer, and this association is modified by genetic variation in the COX-2 gene.

[PMID 16638864] In this study, we identified SNPs in LIG4, ERCC2, and CYP2D6 genes as putative markers to predict individuals at risk for complications arising from radiation therapy in Prostate cancer.

[PMID 16414488] In African American males, CYP3A4 variation rs2740574 is associated with a ~10 fold higher risk of prostate cancer being of an aggressive form.

[PMID 18296681] In prostate cancer patients, rs4880(T;T) individuals who have higher iron intake increase their risk of aggressive cancer.

rs1456315 and rs7463708