Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.

Background: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. Objective: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. Design, setting, and participants: Data from 32 studies that includes 13,790 bladder cancer cases and 343, 502 controls of European ancestry were used for meta-analysis. Outcome measurements and statistical analyses: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. Results and limitations: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 10 8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44–1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. Conclusions: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. Patient summary: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer

Genetic polymorphisms in <it>CYP1A1</it>, <it>GSTM1</it>, <it>GSTP1</it> and <it>GSTT1</it> metabolic genes and risk of lung cancer in Asturias

<p>Abstract</p> <p>Background</p> <p>Metabolic genes have been associated with the function of metabolizing and detoxifying environmental carcinogens. Polymorphisms present in these genes could lead to changes in their metabolizing and detoxifying ability and thus may contribute to individual susceptibility to different types of cancer. We investigated if the individual and/or combined modifying effects of the <it>CYP1A1 MspI</it> T6235C, <it>GSTM1 present/null</it>, <it>GSTT1 present/null</it> and <it>GSTP1 Ile105Val</it> polymorphisms are related to the risk of developing lung cancer in relation to tobacco consumption and occupation in Asturias, Northern Spain.</p> <p>Methods</p> <p>A hospital-based case–control study (CAPUA Study) was designed including 789 lung cancer patients and 789 control subjects matched in ethnicity, age, sex, and hospital. Genotypes were determined by PCR or PCR-RFLP. Individual and combination effects were analysed using an unconditional logistic regression adjusting for age, pack-years, family history of any cancer and occupation.</p> <p>Results</p> <p>No statistically significant main effects were observed for the carcinogen metabolism genes in relation to lung cancer risk. In addition, the analysis did not reveal any significant gene-gene, gene-tobacco smoking or gene-occupational exposure interactions relative to lung cancer susceptibility. Lastly, no significant gene-gene combination effects were observed.</p> <p>Conclusions</p> <p>These results suggest that genetic polymorphisms in the <it>CYP1A1</it>, <it>GSTM1</it>, <it>GSTT1</it> and <it>GSTP1</it> metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions of <it>CYP1A1 Msp</it>I T6235C, <it>GSTM1</it> present/null, <it>GSTT1</it> present/null and <it>GSTP1</it> Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development.</p

The interest of the Spanish network of investigators in back pain for rehabilitation physician

Background: The Spanish Back Pain Research Network (REIDE) brings together teams of researchers and clinicians who are interested in nonspecific neck and back pain (BP). Its objective is to improve the efficacy, safety, effectiveness, and efficiency of the clinical management of BP. Method: The Network welcomes clinicians and researchers interested in BP. The only requirement to become a member of REIDE is to take part in one of its research projects, and any member can propose a new one. The Network supports those projects that are of interest to two or more groups by assuming their administration and management, which allows the researchers to focus on their task. Its working method ensures methodological quality, a multidisciplinary approach, and the clinical relevance of those projects that are carried out. Results: 179 researchers from 11 areas in Spain are involved in REIDE, including experts in all of the relevant fields of BP research. Most Spanish studies on BP that have been published in international scientific journals come from the teams involved in REIDE, and it currently has 13 ongoing research projects. Conclusions: The Network can help to enhance research among rehabilitation specialists who are interested in BP, and can contribute to the development of research projects which are of interest to the specialty. © 2005 Sociedad Española de Rehabilitación y Medicina Física (SERMEF) y Elsevier España, S.L