| 1. |
- Low, Yen Ling, et al.
(författare)
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Multi-Variant Pathway Association Analysis Reveals the Importance of Genetic Determinants of Estrogen Metabolism in Breast and Endometrial Cancer Susceptibility
- 2010
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 6:7, s. e1001012-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML)-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (rho(global) = 0.034) and endometrial (rho(global) = 0.052) cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (rho(global) = 0.008) and endometrial cancer (rho(global) = 0.014). The sub-pathway association was validated in the Finnish sample of breast cancer (rho(global) = 0.015). Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (rho(global) = 0.0003). Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite genetic determinants related to the androgen-estrogen conversion are important for the induction of two hormone-associated cancers, particularly for the hormone-driven breast tumour subtypes.
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| 2. |
- Ji, Guomin, et al.
(författare)
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Enhanced rectifying performance by asymmetrical gate voltage for BDC20 molecular devices
- 2014
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 4:32, s. 16537-16544
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Tidskriftsartikel (refereegranskat)abstract
- By applying the asymmetrical gate voltage on the 1,4-bis (fullero[c]pyrrolidin-1-yl) benzene BDC20 molecule, we investigate theoretically its electronic transport properties using the density functional theory and nonequilibrium Greens function formalism for a unimolecule device with metal electrodes. Interestingly, the rectifying characteristic with very high rectification ratio, 91.7 and 24.0, can be obtained when the gate voltage is asymmetrically applied on the BDC20 molecular device. The rectification direction can be tuned by the different gate voltage applying regions. The rectification behavior is understood in terms of the evolution of the transmission spectrum and projected density of states spectrum with applied bias combined with molecular projected self-consistent Hamiltonian states analyses. Our finding implies that to realize and greatly promote rectifying performance of the BDC20 molecule the variable gate voltage applying position might be a key
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| 3. |
- Ji, Guomin, et al.
(författare)
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Rectifying behaviors of an Au/(C-20)(2)/Au molecular device induced by the different positions of gate voltage
- 2012
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Ingår i: RSC ADVANCES. - : RSC Publishing. - 2046-2069. ; 2:30, s. 11349-11353
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Tidskriftsartikel (refereegranskat)abstract
- The electronic transport properties of a gated Au/(C-20)(2)/Au molecular device are studied using nonequilibrium Greens function in combination with density functional theory. The results show that different applied positions of the external transverse gate voltage can effectively tune the current-voltage (I-V) characteristic of molecular devices. Rectifying behaviors of the device can be realized when the gate voltage is applied asymmetrically on the left C-20 molecule, and the rectification directions can also be modulated by the positive or negative value of the gate voltage. These results provide an important theoretical support to experiments and the design of a molecular rectifier.
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