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- Hálfdánarson, Óskar Ö., et al.
(author)
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Proton pump inhibitor use and risk of breast cancer, prostate cancer, and malignant melanoma : An Icelandic population-based case-control study
- 2019
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In: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 28:4, s. 471-478
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Journal article (peer-reviewed)abstract
- Purpose: Increased expression of Vacuolar-type H+ ATPases (V-ATPases), in the plasma membrane of cancer cells has been suggested to contribute to the development of aggressive cancer phenotypes by promoting acidic tumor microenvironments. Accumulating data suggest that proton pump inhibitors (PPIs) may elicit a chemopreventive effect via V-ATPase inhibition in some cancers, but evidence is still limited. Therefore, we aimed to explore a potential preventive role of PPIs in this study.Methods: In this population-based case-control study, we identified incident cases of breast cancer (n=1739), prostate cancer (n=1897), and malignant melanoma (n=385) in Iceland between 2005 and 2014 from the Icelandic Cancer Registry. We assessed varying levels of PPI use through record linkages to the Icelandic Medicines Registry. For each case, we selected up to 10 age-matched, sex-matched, and calendar-matched population controls using risk-set sampling. Using conditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) controlling for NSAID use.Results: Adjusted ORs associated with ever use of PPIs were 1.03 (95% CI: 0.92-1.16) for breast cancer, 1.12 (95% CI: 1.00-1.25) for prostate cancer, and 0.84 (95% CI: 0.69-1.12) for malignant melanoma. Analyses of high use of PPIs (>= 1000 DDDs) yielded ORs of 0.97 (95% CI: 0.78-1.19), 1.20 (0.99-1.47), and 0.59 (0.40-1.13) for breast cancer, prostate cancer, and malignant melanoma, respectively. Analyses of cumulative exposure to PPIs did not support a dose-response relationship for any of the three cancer types.Conclusions: Our findings do not support a chemopreventive effect of PPI use on breast cancer, prostate cancer, or malignant melanoma.
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- Holl, Katsiaryna, et al.
(author)
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Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case-referent study
- 2009
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:12, s. 2923-2928
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Journal article (peer-reviewed)abstract
- According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs Were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG,). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers With high androstenedione levels had ail increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay or maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. (C) 2009 UICC
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- Holl, Katsiaryna, et al.
(author)
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Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study
- 2008
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In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - Oxford : Wiley. - 1600-0463 .- 0903-4641. ; 116:9, s. 816-822
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Journal article (peer-reviewed)abstract
- During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73: 95% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age(OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.
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- Leosdottir, M., et al.
(author)
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Improving smoking cessation after myocardial infarction by systematically implementing evidence-based treatment methods : a prospective observational cohort study
- 2021
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:Suppl. 1, s. 1409-1409
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Journal article (other academic/artistic)abstract
- Background: For smokers who suffer a myocardial infarction (MI), smoking cessation is the most effective measure to reduce recurrent event risk. Still, evidence-based treatment methods for aiding smoking cessation post-MI are underused.Purpose: To compare the odds of smoking cessation at two-months post-MI before and after implementing a set of pre-specified routines for optimization of evidence-based treatment methods for smoking cessation, with start during admission.Methods: Structured routines for early smoking cessation counselling and treatment optimization were implemented at six cardiac rehabilitation (CR) centres in Sweden. The routines included CR nurses providing current smokers hospitalized for acute MI with short consultation, written material, and optimal dosage of nicotine replacement therapy during admission, increasing early prescription of varenicline for eligible patients, and contacting the patients by telephone 3–5 days after discharge, after which usual care CR follow-up commenced. Centres were also encouraged to strive for continuity in nurse-patient care. Patient data was retrieved from the SWEDEHEART registry and medical records. Using logistic regression, we compared the odds for smoking cessation at two-months post-MI for currently smoking patients admitted with MI (a) before (n=188, median age 60 years, 23% females) and (b) after (n=195, median age 60 years, 29% females) routine implementation. Secondary outcomes included adherence to implemented routines and the association of each routine with smoking cessation odds at two-months.Results: In total, 159 (85%) and 179 (92%) of enrolled patients attended the two-month CR follow-up, before and after implementation of the new routines. After implementation, a significantly larger proportion of patients (65% vs 54%) were abstinent from smoking at two-months (crude OR 1.60 [1.04–2.48], p=0.034) (Figure 1). Including only those counselled during admission (n=89), 74% (vs 54%) were abstinent at two-months (crude OR 2.50 [1.42–4.41], p=0.002). After the new routine implementation patients were counselled more frequently during admission (50% vs 6%, p<0.001), prescribed varenicline at discharge or during follow-up (23% vs 7%, p<0.001), and contacted by telephone during the first week post-discharge (18% vs 2%, p<0.001), compared to before implementation. Crude and adjusted associations between each routine and smoking cessation at two-months are shown in Table 1. Entering all routines into the regression model simultaneously, being prescribed varenicline before discharge or during follow-up had the strongest independent association with smoking abstinence at two-months (adjusted OR 4.09 [1.68–10.00], p=0.002).Conclusion: Our results support that readily available methods for aiding smoking cessation can be implemented effectively in routine practice, with possible beneficial effects on smoking cessation for the high-risk group of smoking MI patients.
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- Luostarinen, T., et al.
(author)
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Human papillomavirus, other sexually transmitted infections and risk of cervical cancer : A Nordic Joint Study
- 2011
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In: IEA World Congress of Epidemiology, 7–11 August 2011, Edinburgh International Conference Centre, Edinburgh, Scotland. - : BMJ. ; 65, s. A266-A266
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Conference paper (peer-reviewed)abstract
- Introduction: Human papillomavirus (HPV) is considered necessary cause of invasive cervical cancer (ICC), but relations between different HPV types and other sexually transmitted infections in cervical carcinogenesis are unresolved. The CCRPB-EU Network conducted a large study, aiming to assess how major high- and low-risk HPV types, 16, 18 and 6, and possible cofactors, Chlamydia trachomatis and herpes simplex virus type 2 (HSV-2), interact in the aetiology of cervical cancer. Methods: A case-control study was nested in four Nordic serum banks containing serum samples from approximately 1 000 000 women. Linkage to cancer registries resulted to 604 ICC cases diagnosed after serum sampling. Five controls were matched to bank, age at sampling and storage time. IgG antibodies specific for HPV types, C trachomatis and HSV-2 were determined, and tobacco smoke exposure measured by serum cotinine, and HPV DNA in cancer tissue PCR-tested. ORs were estimated by conditional logistic regression, and adjusted for cotinine and for HPV16, HPV18 and C trachomatis, when applicable. Results: Seropositivity for HPV16 did not confer any increased risk for HPV18 DNA positive cancer and HPV18 seropositivity had no association with HPV16 DNA positive cancer. HPV6 had no effect on its own but an antagonistic joint effect with HPV16. HSV-2 had little or no association. C trachomatis had a strongly increased risk for cervical cancer, which remained also among HPV18 seropositives. Conclusions: Type-specific HPV DNA persistence is important in cervical carcinogenesis. HSV-2 is possibly not a cofactor, but C trachomatis is probably a strong cofactor for ICC.
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- Pogenberg, Vivian, et al.
(author)
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Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF
- 2012
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In: Genes & Development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 26:23, s. 2647-2658
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Journal article (peer-reviewed)abstract
- Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and an important oncogene in melanoma. MITF heterodimeric assembly with related basic helix-loop-helix leucine zipper transcription factors is highly restricted, and its binding profile to cognate DNA sequences is distinct. Here, we determined the crystal structure of MITF in its apo conformation and in the presence of two related DNA response elements, the E-box and M-box. In addition, we investigated mouse and human Mitf mutations to dissect the functional significance of structural features. Owing to an unusual three-residue shift in the leucine zipper register, the MITF homodimer shows a marked kink in one of the two zipper helices to allow an out-of-register assembly. Removal of this insertion relieves restricted heterodimerization by MITF and permits assembly with the transcription factor MAX. Binding of MITF to the M-box motif is mediated by an unusual nonpolar interaction by Ile212, a residue that is mutated in mice and humans with Waardenburg syndrome. As several related transcription factors have low affinity for the M-box sequence, our analysis unravels how these proteins discriminate between similar target sequences. Our data provide a rational basis for targeting MITF in the treatment of important hereditary diseases and cancer.
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