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- Jochems, Sylvia H.J., et al.
(författare)
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Prediagnostic markers of insulin resistance and prostate cancer risk and death : A pooled study
- 2023
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:12, s. 13732-13744
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundInsulin resistance has been shown to be related to a higher risk of several cancers, but the association with prostate cancer (PCa) has been inconsistent.MethodsWe investigated prediagnostic markers of insulin resistance in men in four cohorts in Sweden, in relation to PCa risk (total, non-aggressive and aggressive) and PCa death using multivariable-adjusted Cox regression. The number of men, PCa cases and PCa deaths was up to 66,668, 3940 and 473 for plasma glucose and the triglyceride-glucose (TyG) index, and up to 3898, 586 and 102 for plasma insulin, glycated haemoglobin (HbA1c) and leptin.ResultsHigher HbA1c was related to a lower risk of non-aggressive PCa but no significant associations were found for insulin resistance markers with the risk of aggressive or total PCa. In PCa cases, higher glucose and TyG index were related to a higher risk of PCa death (hazard ratio [HR] per higher standard deviation, 1.22, 95% CI 1.00–1.49 and 1.24, 95% CI 1.00–1.55), which further increased when restricting the analyses to glucose and TyG index measures taken <10 years before the PCa diagnosis (HR, 1.70, 95% CI 1.09–2.70 and 1.66, 95% CI 1.12–2.51). No associations were observed for other markers in relation to PCa death.ConclusionsThe results of this study showed no associations of insulin resistance markers with the risk of clinically relevant PCa, but higher glucose and TyG index were associated with poorer survival from PCa. The lack of association for other insulin resistance markers may be due to their smaller sample size.
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| 2. |
- Teleka, Stanley, et al.
(författare)
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Association between blood pressure and BMI with bladder cancer risk and mortality in 340,000 men in three Swedish cohorts
- 2021
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 10:4, s. 1431-1438
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relation between obesity, blood pressure (BP) and bladder cancer (BC) risk and mortality remains unclear, partially due to potential confounding by smoking, the strongest risk factor for BC, and not accounting for tumor stage and grade in such studies. We investigated body mass index (BMI) and BP in relation to BC risk by stage and grade, and BC-specific mortality, including separately among never-smokers aimed at minimizing confounding by smoking. Methods: We analyzed 338,910 men from three Swedish cohorts, with 4895 incident BC's (940 among never-smokers) during follow-up. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals adjusted for smoking status. HRs for BMI and BP were corrected for their regression dilution ratios, calculated from 280,456 individuals with 758,641 observations. Results: Body mass index was positively associated with non-muscle invasive BC (NMIBC, HR per 5 kg/m2, 1.10 [1.02–1.19]) and NMIBC grade 3 (HR 1.17 [1.01–1.34]) in the full cohort, with similar effect sizes, albeit non-significant, among never-smokers. Systolic BP was positively associated with muscle-invasive BC (MIBC, HR per 10 mmHg, 1.25 [1.00–1.55]) and BC-specific mortality (HR 1.10 [1.01–1.20]) among never-smokers, with weaker and non-significant associations in the full cohort. Conclusions: In an analyses of BMI, BP and BC risk by stage and grade among men, we found modest positive associations between BMI and NMIBC and NMIBC grade 3. SBP was positively associated with MIBC and BC-specific mortality in an analysis of never-smokers, which may reflect the association, un-confounded by smoking, also in a broader population.
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| 3. |
- Teleka, Stanley, et al.
(författare)
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The interaction between smoking and bladder cancer genetic variants on urothelial cancer risk by disease aggressiveness
- 2022
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 11:15, s. 2896-2905
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSmoking has shown interactions with bladder cancer (BC) genetic variants, especially N-acetyltransferase-2 (NAT2), a tobacco smoke metabolism gene, on BC risk. The interactions by disease aggressiveness are unknown.MethodsWe investigated the interaction between smoking and 18 single nucleotide polymorphisms (SNPs) for BC, individually and in a genetic risk score (GRS), on urothelial cancer (UC) risk including BC. We analysed data from 25,453 individuals with 520 incident UCs during follow-up, 339 non-aggressive (non-fatal, non-muscle invasive) and 163 aggressive (all other) UCs. Hazard ratios (HRs), absolute risks and additive and multiplicative interactions for two-by-two combinations of never/ever smoking with low/high genetic risk were calculated.ResultsSmoking and NAT2 rs1495741 interacted strongly, positively on aggressive UC on both the multiplicative (p = 0.004) and additive (p = 0.0002) scale, which was not observed for non-aggressive UC (pinteractions ≥ 0.6). This manifested in a higher HR of aggressive UC by ever smoking for the slow acetylation NAT2 genotype (HR, 5.00 [95% confidence interval, 2.67–9.38]) than for intermediate/fast acetylation NAT2 (HR, 1.50 [0.83–2.71]), and in differences in absolute risks by smoking and NAT2 genotype. Smoking also interacted additively and positively with the GRS on any UC (p = 0.01) and non-aggressive UC (p = 0.02), but not on aggressive UC (p = 0.1). Gene-smoking interactions of lesser magnitude than for NAT2 were found for SNPs in APOBEC3A, SLC14A1 and MYNN.ConclusionsThis study suggests that smoking increases UC risk more than expected when combined with certain genetic risks. Individuals with the slow acetylation NAT2 variant might particularly benefit from smoking intervention to prevent lethal UC; however, replication in larger studies is needed.
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