CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer: an Italian case-control study

<p>Abstract</p> <p>Background</p> <p>Estrogens, environmental chemicals with carcinogenic potential, as well as oxidative and carbonyl stresses play a very important role in breast cancer (BC) genesis and progression. Therefore, polymorphisms of genes encoding enzymes involved in estrogen biosynthesis pathway and in the metabolic activation of pro-carcinogens to genotoxic intermediates, such as cytochrome P450C17α (CYP17), endogenous free-radical scavenging systems, such as glutathione S-transferase (GSTP1) and paraoxonase 1 (PON1), and anti-glycation defenses, such as glyoxalase I (GLO1), could influence individual susceptibility to BC. In the present case-control study, we investigated the possible association of CYP17 A1A2, GSTP1 ILE105VAL, PON1 Q192R or L55M, and GLO1 A111E polymorphisms with the risk of BC.</p> <p>Methods</p> <p>The above-said five polymorphisms were characterized in 547 patients with BC and in 544 healthy controls by PCR/RFLP methods, using DNA from whole blood. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for BC.</p> <p>Results</p> <p>CYP17 polymorphism had no major effect in BC proneness in the overall population. However, it modified the risk of BC for certain subgroups of patients. In particular, among premenopausal women with the A1A1 genotype, a protective effect of later age at menarche and parity was observed. As to GSTP1 and PON1 192 polymorphisms, the mutant Val and R alleles, respectively, were associated with a decreased risk of developing BC, while polymorphisms in PON1 55 and GLO1 were associated with an increased risk of this neoplasia. However, these findings, while nominally significant, did not withstand correction for multiple testing.</p> <p>Conclusion</p> <p>Genetic polymorphisms in biotransformation enzymes CYP17, GSTP1, PON1 and GLO1 could be associated with the risk for BC. Although significances did not withstand correction for multiple testing, the results of our exploratory analysis warrant further studies on the above mentioned genes and BC.</p

Tidal inlets in the Anthropocene: geomorphology and benthic habitats of the Chioggia inlet, Venice Lagoon (Italy)

Within a multidisciplinary approach, we mapped with unprecedented detail the seafloor morphology, sediment distribution and benthic habitats of a tidal inlet which has been highly impacted by human activity. We identified an unusual habitat for lagoon environment connected to rip-rap used for jetties and hard structures and we estimated that the new pattern of flow around these hard structures caused the erosion of 430 000 m(3) of sediment in eight years

Debating unamendability: deadlock in Turkey's constitution-making process

Constitutional Conciliation Commission (Anayasa Uzlaşma Komisyonu—AUK) of Turkey, established after the 2011 general elections but called off after the commission could not overcome an impasse on a number of issues, was nevertheless a significant step in Turkey’s constitutional development. One of the issues that led to the deadlock in the commission was the issue of unamendable articles. A point of divide among the four parties that made up the commission was whether the new constitution would maintain the eternal clauses of the present constitution that entrench the republic form of the state, its characteristics, and its language or whether it would not include any irrevocable articles. Except the republic’s first constitution of 1921, the three constitutions of modern Turkey included unamendable constitutional provisions, which had previously led to political and constitutional controversies. The subject of unamendable articles was one of the last issues that the commission discussed before the 25 months of enterprise was dissolved. This article traces the evolution of unamendable articles in Turkish constitutions, examines the political parties’ proposals for the draft constitution aand analyzes the debates conducted within AUK. It concludes that members of the AUK held irreconcilable positions with respect to unamendability and unamendable articles, which contributed to the breakdown of the negotiations

Dynamic amplification factor concept of soil layers: a case study in İzmir (Western Anatolia)

Dynamic soil amplification factor (DAF) defining which ratio earthquake acceleration will reach the soil surface by changing is one of the most important factors in seismic risk studies. When computing the value of DAF at a point without a strong motion station, peak horizontal acceleration values (PGA) at the bedrock and soil transfer function are needed. PGA value at the bedrock can be obtained by using either real seismic records or the earthquake scenario. However, the soil transfer function (soil transfer function) can be computed observationally and theoretically. Observational soil transfer function is defined by microtremor horizontal/vertical spectral ratio. In case of theoretical computation, the density belonging to the soil layers between the bedrock and the soil surface is used together with the change of P-S wave rates with the depth and the damping factor. In this study, the dynamic amplification factor (DAF) has been computed and mapped for 57 points by using observational soil transfer functions obtained by microtremor horizontal/vertical spectral ratio as well as the earthquake scenario at a new city center located within the metropolitan area of Izmir. Also, theoretical soil transfer function at 1 point was obtained through spatial autocorrelation method (SPAC) study and determined to be compatible with observational result. It was observed that both peak period values are higher than 1 s and DAF values are higher than 2 throughout the area. Also, according to the soil profile obtained from the SPAC study, S wave rate changes up to a depth of 1300 m showing that acoustic impedance differences may occur in the frequencies and the magnitudes of the earthquake waves. The fact that peak period values obtained from microtremor studies are higher than 2 s supports this result. This means that acoustic impedance differences likely to occur in these depths should also be taken into consideration while computing the dynamic amplification factor