Channel profiles through the active thrust front of the southern Barbados prism.

International audienceSubmarine channels of the Orinoco River were analyzed using high-quality, dense coverage bathymetric and seismic data provided by a recent marine survey on the southern Barbados prism. Analysis of the syntectonic sediments on seismic profiles shows that the four to five frontmost structures show evidence of recent tectonic movement. Slope analysis of the major channels was performed. From their headwaters to domains of little or no active tectonics, the channels display ,0.2% slope and form levees. Slope and incision increase gradually in domains of moderate tectonics, but deep canyons with ;2% mean slope form where the channels cross the active frontal folds of the prism. Detailed correlation between the active structures, their geometry, and canyon slope suggest that systematic variations in channel gradient highlight variations in substrate uplift rate. Steep slopes induced by uplift accelerate sediment flow and enhance incision. Nonetheless, such slope analysis is subject to complications introduced by variations in sediment flux and transient erosional conditions

Brachytherapy for penile cancer: Efficacy and impact on sexual function

AbstractPurposePenis brachytherapy (PB) remains an alternative in the cancer treatment. The objective of this study was to assess the oncologic outcomes, sexual function, and the sexual behavior of men treated by PB for a cancer of the penis.Methods and MaterialsBetween 1992 and 2009, 47 patients with a cancer of the penis were treated by PB (192Ir), in the Toulouse, Montpellier, and Barcelona cancer centers. The investigation into their sexuality was obtained by means of questionnaire. A total of 21 French patients were approached, of whom 19 (mean age=73.2 years) agreed to answer the questionnaire (participation rate=90.5%).ResultsOncologic data: The specific survival and the disease-free survival at 5 years was 87.6% (95% confidence interval, 72.4–94.7%) and 84% (95% confidence interval, 57.6–94.7%), respectively. The rate of preservation of the penis was 66% (n=31). Sexual data: Among the 17 patients sexually active before brachytherapy, 10 patients remained sexually active after treatment (58.8%). Of the 18 patients who had erections before PB, 17 still had them after treatment (94.4%). Age was the main predictive factor.ConclusionThe PB seems to have a moderated impact on the sexual functions and the sexual behavior of the patients

Patient selection for laparoscopic excision of adrenal metastases: a multicenter cohort study

International audienceIntroduction The use of laparoscopy for the excision of adrenal metastasis remains controversial. We aimed to report oncological and perioperative outcomes of laparoscopic excision of adrenal metastases and to seek for predictive factors of unfavourable oncological outcomes. Methods A retrospective chart review was conducted and all consecutive patients who underwent laparoscopic adrenalectomy (LA) in the setting of metastatic cancer in two academic urology departments from November 2006 through January 2014 were included. Primary tumors were categorized as pulmonary, renal or “other primary” tumors to allow statistical comparison. Unfavourable surgical outcomes were defined as the occurrence of either postoperative complications and/or positive surgical margins. Results Forty-three patients who underwent a total of 45 LA were included for analysis. There were 8 complications (17.8%). Positive surgical margins were found in 12 specimens (26.7%). After a median follow-up of 37 months, estimated overall survival rates were 89.5% and 51.5% at 1 year and 5 years, respectively. In multivariable analysis the only predictor of unfavourable surgical outcomes was a tumor size > 5 cm (OR= 20.5; p=0.001). In multivariate analysis the pulmonary (OR=0.3; p=0.008) or “other” (OR= 0.1; p=0.0006) origin of the primary tumor was the only prognostic factor of shorter cancer specific survival. Conclusion Laparoscopic resection of adrenal metastasis can be safely performed in most patients but is associated with an increased risk of positive surgical margins and postoperative complications in larger tumors (>5 cm). Adrenalectomy provides better oncological outcomes in metastases from renal cell carcinoma compared to other primary tumors

A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Geneenvironment interactions (G x E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G x E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G x E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G x E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant GxBMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures