Wednesday, February 25, 2009

Predictive ability of SNPs for prostate cancer

Utility of Incorporating Genetic Variants for the Early Detection of Prostate Cancer
Robert K. Nam, William W. Zhang, John Trachtenberg, Arun Seth, Laurence H. Klotz, Aleksandra Stanimirovic, Sanoj Punnen, Vasundara Venkateswaran, Ants Toi, D. Andrew Loblaw, Linda Sugar, Katherine A. Siminovitch, Steven A. Narod
Clinical Cancer Research, 10.1158/1078-0432
Abstract Purpose: Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated.Experimental Design: We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy.Results: Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P = 0.02-7 x 10-8). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P = 0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve = 0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P = 1 x 10-15).Conclusions: SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.

Wednesday, February 18, 2009

Teaching material for evolution by natural selection

In honor of Darwin's recent 200th birthday, Nature came up with a list of 15 Evolutionary Gems. My major complaint, and a pretty major one at that, is that none of the examples are related to human evolution - something that students could probably relate to a bit more easily, and might increase the chance that they actually pay attention.
Basically, what I'm getting at: Why is lactase persistence not there? or the several other well-documented and clear cut examples from human evolution?

Elucidating the genetics of eye color

Getting closer to predicting not-so-complex "complex" phenotypes from genetic data?
Eye and skin color are great model phenotypes with which we can learn about the genetics of complex traits, as I've often argued. Here's another step in the process.

Interactions Between HERC2, OCA2 and MC1R May Influence Human Pigmentation Phenotype.
Branicki W, Brudnik U, Wojas-Pelc A.
Ann Hum Genet. 2009 Feb 4. [Epub ahead of print]
Abstract: Human pigmentation is a polygenic trait which may be shaped by different kinds of gene-gene interactions. Recent studies have revealed that interactive effects between HERC2 and OCA2 may be responsible for blue eye colour determination in humans. Here we performed a population association study, examining important polymorphisms within the HERC2 and OCA2 genes. Furthermore, pooling these results with genotyping data for MC1R, ASIP and SLC45A2 obtained for the same population sample we also analysed potential genetic interactions affecting variation in eye, hair and skin colour. Our results confirmed the association of HERC2 rs12913832 with eye colour and showed that this SNP is also significantly associated with skin and hair colouration. It is also concluded that OCA2 rs1800407 is independently associated with eye colour. Finally, using various approaches we were able to show that there is an interaction between MC1R and HERC2 in determination of skin and hair colour in the studied population sample.
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