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- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 2. |
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| 3. |
- Djavan, Bob, et al.
(författare)
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Testosterone in prostate cancer: the Bethesda consensus.
- 2012
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Ingår i: BJU International. - 1464-4096. ; 110:3, s. 344-352
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Tidskriftsartikel (refereegranskat)abstract
- What's known on the subject? and What does the study add? Androgen stimulation of prostate cancer (PCa) cells has been the basis for extensive studies evaluating the role of androgen in PCa but the diagnostic measurement of androgen as well as androgen values that potentially influence prognosis are unclear in patients with PCa. The 50 ng/dL threshold has been questioned as a result of reports indicating worse outcomes for levels between 20 and 50 ng/dL. Instead, a 20 ng/dL threshold for serum testosterone after androgren deprivation therapy in patients with advanced PCa was recommended. OBJECTIVE: • Androgen stimulation of prostate cancer (PCa) cells has been extensively studied. The increasing trend of using serum testosterone as an absolute surrogate for castration state means that the diagnostic measurement of testosterone and the values potentially influencing prognosis must be better understood. This is especially important when PCa progresses from an endocrine to an intracrine status. PATIENTS AND METHODS: • We performed a literature review using the MEDLINE database for publications on: (i) hormonal changes with androgen deprivation therapy (ADT); (ii) monitoring hormonal therapy with testosterone measurement; (iii) the efficacy of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation; (iv) the underlying mechanisms of castration-resistance; and (v) novel treatments for castration-resistant PCa (CRPCa). RESULTS: • The optimum serum castration levels to be achieved with ADT are still debated. Recently, the 50 ng/dL threshold has been questioned because of reports indicating worse outcomes when levels between 20 and 50 ng/dL were studied. Instead, a 20 ng/dL threshold for serum testosterone after ADT in patients with advanced prostate cancer was recommended. CONCLUSION: • Understanding the mechanisms of androgen biosynthesis relating to PCa as well as prognostic implications might achieve a consensus regarding the role of ADT for both the androgen-sensitive and -insensitive disease state.
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