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- Hollestelle, Antoinette, et al.
(author)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Journal article (peer-reviewed)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 2. |
- Hagmar, Lars, et al.
(author)
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Epidemiological evaluation of cytogenetic biomarkers as potential surrogate end-points for cancer.
- 2004
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In: Mechanisms of Carcinogenesis (IARC Sci. Publ. ; 157). - 9283221575 - 9789283221579 ; :157, s. 207-215
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Book chapter (other academic/artistic)abstract
- Various occupational exposures have been monitored by chromosomal aberrations, sister chromatid exchanges and micronuclei in peripheral blood lymphocytes. During the last decade, epidemiological studies have evaluated whether any of these markers foreshadows cancer risk. Results from Nordic, Italian and Czech cohorts support an approximately twofold cancer risk among subjects with high frequencies of chromosomal aberrations, but no such association was seen for any of the other biomarkers. The estimated attributable proportion of high frequencies of chromosomal aberrations for overall cancer risk is 0.25, which gives a quantitative estimate of the chromosomal aberration assay as a surrogate endpoint of cancer. The results from the different cohort studies are contradictory in terms of whether or not the predictive value of the chromosomal aberration assay for cancer is differential with respect to occupational exposure to clastogens. Genetic susceptibility factors are known to affect the frequency of chromosomal aberrations in peripheral blood lymphocytes. It is quite possible that such factors might also affect the frequency of chromosomal aberrations directly or might modify the impact of exposures to clastogen. There is no other biomarker for general cancer risk that is applicable to healthy subjects from the general population with such a high attributable proportion. However, at present only a simplified and tentative model can be proposed for the role of the chromosomal aberration marker in the pathogenesis of cancer.
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| 4. |
- Wang, Ailing, et al.
(author)
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Mildly relativistic motion in the radio-quiet quasar PG 1351+640
- 2023
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In: Monthly Notices of the Royal Astronomical Society: Letters. - 1745-3925 .- 1745-3933. ; 523:1, s. L30-L34
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Journal article (peer-reviewed)abstract
- Measuring the proper motion of the emission component in radio-quiet quasars (RQQs) could help to distinguish between the origins of the radio emission and to understand whether the jet production mechanism is the same in radio-loud quasars and RQQs. PG 1351+640 is one of the few RQQs suitable for proper motion studies: it has two compact components on milli-arcsec scales, a flat-spectrum core and a steep-spectrum jet; both components are ≳2 mJy at 5 GHz and are well suited for Very Long Baseline Array (VLBA) observations. We compare recent VLBA observations with that made seventeen years ago and find no significant change in the core-jet separation between 2005 and 2015 (a proper motion of 0.003 mas yr-1). However, the core-jet separation increased significantly between 2015 and 2022, inferring a jet proper motion velocity of 0.063 mas yr-1, which corresponds to an apparent transverse velocity of. The result suggests that the jet of the RQQ PG 1351+640 is mildly relativistic and oriented at a relatively small viewing angle.
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