| 1. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 3. |
- Chen, Daru, et al.
(author)
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Actively mode-locked fiber laser based on hybrid Raman and erbium-doped fiber gains
- 2007
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In: Microwave and optical technology letters (Print). - : Wiley. - 0895-2477 .- 1098-2760. ; 49:10, s. 2339-2341
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Journal article (peer-reviewed)abstract
- An actively mode-locked fiber laser (AMLFL) based on the hybrid gain of a dispersion-shifted fiber (as the Raman gain medium) and an Erbium-doped fiber (EDF) is introduced. The fiber Raman gain mechanism can effectively suppress the gain competition of an EDF, which usually results into the supermode noise in an actively mode-locked EDF laser. We experimentally demonstrated a stable AMLFL with the repetition of about 5 GHz, in which the supermode noise is believed to be suppressed by employing the hybrid gain medium.
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| 6. |
- Chen, Daru R., et al.
(author)
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Wavelength-spacing continuously tunable multi-wavelength SOA-fiber ring laser based on Mach-Zehnder interferometer
- 2008
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In: Optics and Laser Technology. - : Elsevier BV. - 0030-3992. ; 40:2, s. 278-281
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Journal article (peer-reviewed)abstract
- A Mach-Zehnder interferometer (MZI) which is used as a wavelength-spacing tunable comb filter in a fiber ring laser is built by employing an optical variable delay line (OVDL). Stable multi-wavelength semiconductor optical amplifier (SOA)-fiber ring laser based on an SOA and the MZI comb filter is achieved. Wavelength spacing can be continuously tuned by adjusting the OVDL and, as an example, multi-wavelength lasing with the wavelength spacing of 0.4, 0.8, or 1.6 nm is demonstrated. The output of the proposed multi-wavelength SOA-fiber ring laser is quite stable at room temperature and the output spectrum can be adjusted by controlling the bias current of the SOA.
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| 7. |
- Chen, Daru, et al.
(author)
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Single-longitudinal-mode erbium-doped fiber laser based on a fiber Bragg grating Fabry-Perot filter
- 2007
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In: Laser physics. - 1054-660X .- 1555-6611. ; 17:10, s. 1246-1248
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Journal article (peer-reviewed)abstract
- A novel single-longitudinal-mode (SLM) erbium-doped fiber laser with a simple linear cavity based on a fiber Bragg grating Fabry-Perot filter (FBG-FPF) and a narrowband (similar to 0.06 nm) FBG is proposed and demonstrated experimentally. Two uniform FBGs form the FBG-FPF, which has two ultranarrow transmission bands with a bandwidth of 0.12 pm and a wavelength spacing of 0.095 nm. By slightly tuning the central wavelength of the narrowband FBG, SLM lasing at 1549.658 or 1549.563 nm (corresponding to the two transmission peaks of the FBG-FPF) is achieved with a laser output power of similar to 4 mW, when the pump power is similar to 75 mW.
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| 8. |
- Chen, Daru, et al.
(author)
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Some switchable dual-wavelength fibre lasers based on fibre Bragg grating feedback
- 2006
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In: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 6351, s. U864-U872
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Journal article (peer-reviewed)abstract
- Two methods to achieve dual-wavelength switching in a fibre laser are proposed and two corresponding switchable dual-wavelength fibre lasers based on fibre Bragg grating (FBG) feedback are demonstrated in this paper. In one proposed fibre laser, both Raman and Erbium-doped fibre (EDF) pumps are employed and the dual-wavelength switching is achieved by controlling the power of the Raman pump. In the other proposed fibre laser, an injection technique is used and the dual-wavelength switching is realized by controlling the power of the injection laser. The detailed behavior of the dual-wavelength switching in the two fibre lasers is experimentally studied and the principle is explained physically.
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| 9. |
- Chen, Daru
(author)
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Stable multi-wavelength erbium-doped fiber laser based on a photonic crystal fiber Sagnac loop filter
- 2007
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In: LASER PHYSICS LETTERS. - : IOP Publishing. - 1612-2011 .- 1612-202X. ; 4:6, s. 437-439
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Journal article (peer-reviewed)abstract
- A multi-wavelength erbium-doped fiber laser based on a Sagnac loop fiber which is formed by a birefringent and highly nonlinear photonic crystal fiber (PCF), a 3-dB optical coupler and two polarization controllers is proposed. The PCF Sagnac loop filter is used as comb filter and power-stabilizing and equilibrizing component in the multi-wavelength erbium-doped fiber laser. Stable multi-wavelength lasing at room temperature is achieved, owing to the contributions of both the birefringent property and the four-wave mixing effect of the PCF.
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| 10. |
- Chen, Daru, et al.
(author)
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Switchable and tunable Erbium-doped fiber ring laser incorporating a birefringent and highly nonlinear photonic crystal fiber
- 2007
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In: LASER PHYSICS LETTERS. - : IOP Publishing. - 1612-2011 .- 1612-202X. ; 4:5, s. 368-370
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Journal article (peer-reviewed)abstract
- A birefringent and highly nonlinear photonic crystal fiber is employed in an Erbium doped fiber ring laser, which can operate with dual-wavelength lasing or single-wavelength lasing. Both stable dual-wavelength lasing and tunable single-wavelength lasing are achieved by adjusting a polarization controller in the ring cavity. The experimental results show that the output of the proposed fiber ring laser is rather stable at two different operation modes.
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