Use of oral glucocorticoids and risk of skin cancer and non-Hodgkin's lymphoma: a population-based case–control study

Jensen, Annette Østergaard; Thomsen, Henrik F.; Engebjerg, Malene Cramer; Olesen, Anne Braae; Friis, Søren; Karagas, Margaret R.; Sørensen, Henrik Toft

doi:10.1038/sj.bjc.6604796

Cited by 84 publications

(76 citation statements)

References 21 publications

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“…A late consequence of such aberrant mitosis, in the event that death in mitosis is avoided, is survival of aneuploid cells with accumulation of DNA damage (37). We identified a complex cell cycle phenotype resulting from loss of GR expression.…”

Section: Discussionmentioning

confidence: 89%

“…The role of GR in cancer has received some attention, but, to date, no clear phenotype has emerged. Gc use, and therefore activation of GR, has been linked with an increased risk of developing skin and bladder cancer (37,39). However, none of the small number of patients with GR genetic defects and familial Gc resistance has developed cancer.…”

Section: Discussionmentioning

confidence: 99%

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Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy

Matthews

Berry

Morgan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily, which controls programs regulating cell proliferation, differentiation, and apoptosis. We have identified an unexpected role for GR in mitosis. We discovered that specifically modified GR species accumulate at the mitotic spindle during mitosis in a distribution that overlaps with Aurora kinases. We found that Aurora A was required to mediate mitosis-driven GR phosphorylation, but not recruitment of GR to the spindle. GR was necessary for mitotic progression, with increased time to complete mitosis, frequency of mitotic aberrations, and death in mitosis observed following GR knockdown. Complementation studies revealed an essential role for the GR ligand-binding domain, but no clear requirement for ligand binding in regulating chromosome segregation. The GR N-terminal domain, and specifically phosphosites S203 and S211, were not required. Reduced GR expression results in a cell cycle phenotype, with isolated cells from mouse and human subjects showing changes in chromosome content over prolonged passage. Furthermore, GR haploinsufficient mice have an increased incidence of tumor formation, and, strikingly, these tumors are further depleted for GR, implying additional GR loss as a consequence of cell transformation. We identified reduced GR expression in a panel of human liver, lung, prostate, colon, and breast cancers. We therefore reveal an unexpected role for the GR in promoting accurate chromosome segregation during mitosis, which is causally linked to tumorigenesis, making GR an authentic tumor suppressor gene.glucocorticoid receptor | mitosis | aneuploidy | DNA damage | cancer G lucocorticoids (Gcs) act through the glucocorticoid receptor (GR), a member of the nuclear hormone receptor superfamily, and a ligand-activated transcription factor (1-4). The GR is ubiquitously expressed and regulates energy metabolism, immunity, and cell fate decisions. The quiescent GR resides in the cytoplasm in a complex with heat shock proteins and immunophilins, attached to the microtubule architecture of the cell in a heat shock protein 90-dependent manner (5). Ligand binding drives GR transformation, involving N-terminal phosphorylation on S203 and S211 and rapid translocation to the nucleus requiring attachment to dynein by heat shock protein 90, immunophilins, and dynamitin (6). Once in the nucleus, GR binds directly to DNA to regulate transcription, or tethers to other DNA-bound transcription factors, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP1), to regulate their function (7-10).In mitosis, GR is phosphorylated on both S203 and S211, but in a ligand-independent manner (11), and more comprehensive phosphoproteomic analyses identify the presence of multiple N-terminal GR phosphoforms in purified mitotic spindle fractions (12). Although altered GR function in mitosis has been shown (11, 13, 14), the kinases responsible and cellular consequences have not been defined. The role of G...

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy

Matthews

Berry

Morgan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…28,29,36 This incompleteness hypothetically may bias our results in 2 ways. On 1 hand, if NSAID users have higher comorbidity than nonusers, then some clinicians may deem the detection of a keratinocyte carcinoma relatively trivial and not as important to register as other comorbidities, thereby producing a false inverse association between NSAIDs and SCC or BCC risk.…”

Section: Discussionmentioning

confidence: 99%

Nonsteroidal anti‐inflammatory drugs and the risk of skin cancer

Johannesdottir

Chang

Mehnert

et al. 2012

Cancer

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BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, which are involved in carcinogenesis. Therefore, the authors of this report examined the association between NSAID use and the risk of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: From 1991 through 2009, all incident cases of SCC (n ¼ 1974), BCC (n ¼ 13,316), and MM (n ¼ 3242) in northern Denmark were identified. Approximately 10 population controls (n ¼ 178,655) were matched to each case by age, gender, and county of residence. The use of aspirin, other nonselective NSAIDs, or selective COX-2 inhibitors was ascertained through a prescription database. Conditional logistic regression analyses adjusted for potential confounders were used to compute odds ratios as estimates of incidence rate ratios (IRRs). RESULTS: For NSAIDs overall, ever use (>2 prescriptions) compared with nonuse ( 2 prescriptions) was associated with a decreased risk of SCC (IRR, 0.85; 95% confidence interval [CI], 0.76-0.94) and MM (IRR, 0.87; 95% CI, 0.80-0.95), especially for long-term use (!7 years) and high-intensity use (>25% prescription coverage during the total duration of use). NSAID use was not associated with a reduced risk of BCC overall (IRR, 0.97; 95% CI, 0.93-1.01), but the risk of BCC at sites other than the head and neck was reduced in association with long-term use (IRR, 0.85; 95% CI,) and high-intensity use (IRR, 0.79; 95% CI, 0.69-0.91). All estimates of reduced risk were driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors (diclofenac, etodolac, and meloxicam). CONCLUSIONS: The current results indicated that NSAID use may decrease the risk of SCC and MM.

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“…A positive correlation was noted compared with 57 cases of basal cellular cancer per 40 expected (RR = 1.41) and squamous cell carcinoma of 7 cases per 3 expected (RR = 2.48) [17]. The research on allergic rhinitis and other allergies with a complex clinical picture is equally inconclusive.…”

Section: Discussionmentioning

confidence: 95%

The link between neoplastic and atopic diseases

Kozłowska

Bożek

Jarząb

2017

Ann. Acad. Med. Siles.

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WstępOchronny lub stymulujący wpływ atopii na ryzyko rozwoju nowotworu pozostaje otwartym pytaniem. Dotychczasowe prace naukowe analizujące temat przynoszą różne odpowiedzi. W pracy badano występowanie chorób nowotworowych u pacjentów z potwierdzonymi chorobami atopowymi w stosunku do grupy kontrolnej bez cech atopii.Materiał i metodyU 1451 pacjentów z chorobą atopową oraz 1389 osób stanowiących grupę kontrolną w wieku powyżej 35 r.ż. wykonano badanie, alergiczne testy skórne, oznaczono stężenie alergenowo swoistych przeciwciał IgE przeciwko najczęstszym alergenom wziewnym. Przeprowadzono analizę dokumentacji medycznej oraz wypełniono oryginalny kwestionariusz zawierający między innymi pytania o ewentualne występowanie chorób nowotworowych i alergii u pacjenta oraz w jego rodzinie. Dodatkowo wykonano oznaczenia następujących markerów nowotworowych w surowicy krwi AFP, CEA, SCC, PSA, Ca 15.3, Ca 19-9, Ca 125, HCG, CYFRA 21-1.WynikiWyniki potwierdziły brak istotnej różnicy w częstości występowania większości analizowanych nowotworów pomiędzy badanymi grupami. Odnotowano znacznie mniejszą zachorowalność na przewlekłą białaczkę szpikową oraz przewlekłą białaczkę limfatyczną w grupie badanej. Zaobserwowano ujemną korelację pomiędzy wartością stężenia całkowitej IgE w surowicy krwi a prawdopodobieństwem rozpoznania choroby nowotworowej w grupie badanej. Wśród pacjentów z chorobą atopową obserwowano wyższe stężenie markeru CYFRA 21-1 w surowicy krwi, lecz bez manifestacji klinicznej.WnioskiWystępowanie choroby nowotworowej jest nieznacznie niższe u pacjentów z chorobami atopowymi niż w grupie kontrolnej bez alergii. Nie odnotowano istotnych różnic w analizowanych markerach nowotworowych surowicy krwi pomiędzy grupami.

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Use of oral glucocorticoids and risk of skin cancer and non-Hodgkin's lymphoma: a population-based case–control study

Cited by 84 publications

References 21 publications

Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy

Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy

Nonsteroidal anti‐inflammatory drugs and the risk of skin cancer

The link between neoplastic and atopic diseases

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