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- Bouras, Emmanouil, et al.
(författare)
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Genome-wide interaction analysis of folate for colorectal cancer risk
- 2023
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 118:5, s. 881-891
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate.Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.
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| 4. |
- Walther, Andreas, et al.
(författare)
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Analysis of the potential for non-invasive imaging of oxygenation at heart depth, using ultrasound optical tomography (UOT) or photo-acoustic tomography (PAT)
- 2017
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Ingår i: Biomedical Optics Express. - 2156-7085. ; 8:10, s. 4523-4536
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Tidskriftsartikel (refereegranskat)abstract
- Despite the important medical implications, it is currently an open task to find optical non-invasive techniques that can image deep organs in humans. Addressing this, photo-acoustic tomography (PAT) has received a great deal of attention in the past decade, owing to favorable properties like high contrast and high spatial resolution. However, even with optimal components PAT cannot penetrate beyond a few centimeters, which still presents an important limitation of the technique. Here, we calculate the absorption contrast levels for PAT and for ultrasound optical tomography (UOT) and compare them to their relevant noise sources as a function of imaging depth. The results indicate that a new development in optical filters, based on rare-earth-ion crystals, can push the UOT technique significantly ahead of PAT. Such filters allow the contrastto- noise ratio for UOT to be up to three orders of magnitude better than for PAT at depths of a few cm into the tissue. It also translates into a significant increase of the image depth of UOT compared to PAT, enabling deep organs to be imaged in humans in real time. Furthermore, such spectral holeburning filters are not sensitive to speckle decorrelation from the tissue and can operate at nearly any angle of incident light, allowing good light collection. We theoretically demonstrate the improved performance in the medically important case of non-invasive optical imaging of the oxygenation level of the frontal part of the human myocardial tissue. Our results indicate that further studies on UOT are of interest and that the technique may have large impact on future directions of biomedical optics.
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| 5. |
- Xia, Zhiyu, et al.
(författare)
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Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.
- 2020
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:10, s. 3563-3573
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2.RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ).CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.
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| 6. |
- Zhang, Huiliang, et al.
(författare)
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Slow light for deep tissue imaging with ultrasound modulation
- 2012
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 100:13
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Tidskriftsartikel (refereegranskat)abstract
- Slow light has been extensively studied for applications ranging from optical delay lines to single photon quantum storage. Here, we show that the time delay of slow-light significantly improves the performance of the narrowband spectral filters needed to optically detect ultrasound from deep inside highly scattering tissue. We demonstrate this capability with a 9 cm thick tissue phantom, having 10 cm(-1) reduced scattering coefficient, and achieve an unprecedented background-free signal. Based on the data, we project real time imaging at video rates in even thicker phantoms and possibly deep enough into real tissue for clinical applications like early cancer detection. VC 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3696307]
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