Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland.
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AuthorsAdalsteinsson, Jonas A
Silverberg, Jonathan I
Olafsdottir, Gudridur H
Kristjansson, Arni Kjalar
Jonasson, Jon Gunnlaugur
MetadataShow full item record
CitationAdalsteinsson JA, Muzumdar S, Waldman R, Wu R, Ratner D, Feng H, Ungar J, Silverberg JI, Olafsdottir GH, Kristjansson AK, Tryggvadottir L, Jonasson JG. Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland. J Am Acad Dermatol. 2021 Jul;85(1):56-61. doi: 10.1016/j.jaad.2021.02.042.
AbstractBackground: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. Objectives: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. Methods: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. Results: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). Limitations: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. Conclusion: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies. Keywords: basal cell carcinoma; keratinocyte carcinoma; metformin; squamous cell carcinoma; squamous cell carcinoma in situ.
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RightsCopyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
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Nuclear DNA analysis and prognosis in carcinoma of the thyroid gland. A nationwide study in Iceland on carcinomas diagnosed 1955-1990Jonasson, J G; Hrafnkelsson, J; Department of Pathology, University of Iceland, Reykjavík. (Springer, 1994-01)The purpose of this study was to ascertain whether DNA ploidy status and S-phase fraction affected the prognosis of patients with carcinoma of the thyroid gland. We reviewed all malignant thyroid tumours diagnosed in Iceland from 1955 to 1990. In all, 494 thyroid carcinomas were diagnosed during that period. By analysing tumour material from paraffin blocks by flow cytometry we were able to evaluate the ploidy status in 424 tumours and the S-phase value in 417 tumours. We detected aneuploid cell populations in 9.7% of papillary carcinomas, 24.3% of follicular carcinomas, 42.9% of medullary carcinomas and 78.6% of anaplastic carcinomas. Some 57% of tumours, mainly papillary carcinomas, had an S-phase value of less then 3%, whereas most of the other histological types of carcinoma, including all the anaplastic tumours, had an S-phase value of > or = 3%. Univariate analysis indicated that both ploidy status and S-phase fraction were significant variables. When taking into account known prognostic variables of thyroid carcinoma in a multivariate analysis, however, neither ploidy status nor S-phase value proved significant. We conclude that DNA ploidy status and S-phase values are not independent prognostic factors in thyroid carcinoma.
Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study.Adalsteinsson, Jonas A; Muzumdar, Sonal; Waldman, Reid; Hu, Chaoran; Wu, Rong; Ratner, Désirée; Ungar, Jonathan; Silverberg, Jonathan I; Olafsdottir, Gudridur H; Kristjansson, Arni Kjalar; et al. (Elsevier, 2020-08-11)Background: Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking. Objectives: To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC). Methods: This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use. Results: A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29). Limitations: Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. Conclusions: High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ. Keywords: basal cell carcinoma; epidemiology; hydrochlorothiazide; keratinocyte carcinoma; squamous cell carcinoma.
Carcinoma ani á Íslandi 1987-2003 : lýðgrunduð rannsóknHalla Viðarsdóttir; Páll Helgi Möller; Jakob Jóhannsson; Jón Gunnlaugur Jónasson (Læknafélag Íslands, Læknafélag Reykjavíkur, 2006-05-01)OBJECTIVE: Anal cancer is a rare disease. The aim of this study was to describe anal cancer in Iceland in 1987-2003 with respect to incidence, histologic type, treatment, recurrence rate and survival. MATERIAL AND METHODS: This is a retrospective study in which all malignant anal tumours diagnosed in Iceland in the period 1987-2003 were reviewed with respect to patient outcome. Information was obtained from hospitals registers. All histological material was reviewed by a consultant histopathologist (JGJ). This is a nationwide, population-based study of malignant tumours of the anal region. RESULTS: From 1987-2003 thirty-eight patients were diagnosed with anal cancer, 28 females and 10 males. The average age at diagnosis was 63.4 years. Age standardized incidence rates for anal cancer in Iceland were 0.3 (+/-0.2) of 100.000 males and 0.9 (+/-0.4) of 100.000 females. Most patients had squamous cell carcinoma (n=30). The remaining histologic types were malignant melanoma (n=3), adenosquamous carcinoma (n=1), adenocarcinoma (n=1), GIST (n=1) and undifferentiated carcinoma (n=2). The most common symptoms were rectal bleeding (n=27), mass lesion (n=28), pain (n=19) and pruritus (n=4). Most patients had more than one symptom. The duration of symptoms before diagnosis ranged from 2 weeks to 96 months (mean value 3.5 months). Treatment modalities used were chemotherapy (n=12), radiotherapy (n=25) and local excision (n=18) and/or APR (n=5). One patient received no treatment. Many patients were treated with more than one treatment modality (n=18). Twelve patients had recurrent cancer. The mean value of the time from diagnosis of the primary to the recurrent cancer was 15.6 months (range, 5.9-117). Sixteen patients remain with disease and ten have died of anal cancer. The five year survival rate for patients diagnosed in the years 1987 to 1998 is 75% but cancer-specific survival is 82%. CONCLUSION: Age-standardized incidence for anal cancer in Iceland is similar to other regions. Average age at diagnosis, male-female ratio and prognosis is similar to reports in other studies. The proportion of adenocarcinoma of the anus is lower in Iceland than elsewhere.