Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression

Background Besides serum levels of PSA, there is a lack of prostate cancer specific biomarkers. It is need to develop new biological markers associated with the tumor behavior which would be valuable to better individualize treatment. The aim of this study was to elucidate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and prostate cancer progression.Methods A total of 494 prostate cancer patients from a Spanish multicenter study were genotyped for 10 SNPs in XRCC1, ERCC2, ERCC1, LIG4, ATM and TP53 genes. The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. Clinical tumor stage, diagnostic PSA serum levels, and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator.Results SNPs rs11615 (ERCC1) and rs17503908 (ATM) appeared as risk factors for prostate cancer aggressiveness. Patients wild homozygous for these SNPs (AA and TT, respectively) were at higher risk for developing cT2b – cT4 (OR = 2.21 (confidence interval (CI) 95% 1.47 – 3.31), p < 0.001) and Gleason scores ≥ 7 (OR = 2.22 (CI 95% 1.38 – 3.57), p < 0.001), respectively. Moreover, those patients wild homozygous for both SNPs had the greatest risk of presenting D’Amico high-risk tumors (OR = 2.57 (CI 95% 1.28 – 5.16)).Conclusions Genetic variants at DNA repair genes are associated with prostate cancer progression, and would be taken into account when assessing the malignancy of prostate cancer.This work was subsidized by a grant from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad from Spain), ID: PI12/01867. Almudena Valenciano has a grant from the Instituto Canario de Investigación del Cáncer (ICIC)

Urban and Transport Scaling: Northern Mesopotamia in the Late Chalcolithic and Bronze Age

Scaling methods have been applied to study modern urban areas and how they create accelerated, feedback growth in some systems while efficient use in others. For ancient cities, results have shown that cities act as social reactors that lead to positive feedback growth in socioeconomic measures. In this paper, we assess the relationship between settlement area expressed through mound area from Late Chalcolithic and Bronze Age sites and mean hollow way widths, which are remains of roadways, from the Khabur Triangle in northern Mesopotamia. The intent is to demonstrate the type of scaling and relationship present between sites and hollow ways, where both feature types are relatively well preserved. For modern roadway systems, efficiency in growth relative to population growth suggests roads should show sublinear scaling in relation to site size. In fact, similar to modern systems, such sublinear scaling results are demonstrated for the Khabur Triangle using available data, suggesting ancient efficiency in intensive transport growth relative to population levels. Comparable results are also achieved in other ancient Near East regions. Furthermore, results suggest that there could be a general pattern relevant for some small sites (0–2 ha) and those that have fewer hollow ways, where β, a measure of scaling, is on average low (≈ < 0.2). On the other hand, a second type of result for sites with many hollow ways (11 or more) and that are often larger suggests that β is greater (0.23–0.72), but still sublinear. This result could reflect the scale in which larger settlements acted as greater social attractors or had more intensive economic activity relative to smaller sites. The provided models also allow estimations of past roadway widths in regions where hollow ways are missing