Antihypertensive (anti-HT) drugs targeting renin-angiotensin-aldosterone (RAA)- system have been associated with improved prostate cancer (PCa)-specific survival. Challenge is that often multiple drugs are used simultaneously. We evaluated the association between use of anti-HT drugs and PCa survival among 14,422 surgically treated Finnish PCa patients. Information on drug purchases was obtained from a national prescription database. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of PCa death and initiation of androgen deprivation therapy (ADT) with adjustment for age, tumor extent, use of statins and for Charlson Comorbidity Index. Angiotensin-converting enzyme (ACE)- inhibitors, angiotensin- receptor (ATR)-blockers, diuretics, calcium-channel blockers, beta-blockers and other anti-HT drugs were analyzed as separate time-dependent variables to model simultaneous use. Overall anti-HT drugs were associated with an increased risk of PCa death. Conversely use of ATR-blockers was associated with decreased risk of PCa death (HR: 0.43, 95% CI: 0.26-0.72 and HR: 0.60, 95% CI 0.37-0.97 for pre- and post-diagnostic use). Similar risk decrease was not observed in other drug groups. Anti-HT drugs were also associated with an increased risk of starting ADT, with the exception of ATR-blockers (HR: 0.81 CI:0.71-0.92). ATR- blockers differ from other anti-HT drugs as the survival is better in users of this drug group. The result partly supports the role of RAA system in PCa progression. Nevertheless, the risk decrease was not observed in ACE-inhibitor users. Further research is needed to elucidate the molecular mechanism for the potential anticancer effect of ATR- blockers.

Introduction: Breast cancer (BCa) has been associated with hypertension which might adversely affect disease prognosis. It is however unclear whether use of anti-HT drugs would improve BCa prognosis. Materials and Methods: A cohort of 73,170 women diagnosed BCa during 1995-2013 identified from the Finnish Cancer Registry and information on anti-HT drug use based on national prescription database during the same time period was combined. Anti-HT drug use was analysed separately by drug use before and after BCa diagnosis. Analyses were performed using timedependent variables for use of each six anti-HT drug group, statins, antidiabetic drugs and anticoagulative drugs to model for simultaneous use of multiple drugs. Association between cumulative dose, duration and intensity of anti-HT drug use and risk of BCa death was evaluated. Results: In pre-diagnostic use only ATR-blockers associated with decreased risk of BCa death compared to non-users (HR: 0.76 95% CI: 0.69-0.82) and risk decreased in inverse association with cumulative dose and duration of use. Diuretics and furosemide associated with statistically significant increase in BCa death risk.In post-diagnostic analyses ATR-blockers and also ACE-inhibitors, beta-blockers and calciumchannel blockers were associated with better BCa survival compared to non users. The results were dose-dependent in all mentioned drug groups. The risk decrease was however highest among users of ATR-blockers (HR: 0.69 95% CI: 0.63-0.75).Conclusions: ATR-blockers were the only antihypertensive drug group associated with improved BCa survival in both pre-and post-diagnostic use. The association was dose-dependent and supported by biological rationale which suggests a direct, causal explanation. However, for postdiagnostic use similar lowering was found also for other anti-HT groups which also supports prognostic role of hypertension control. Risk estimates for post-diagnostic ATR-blocker use were however lower compared to others drug groups. Inhibiting angiotensin receptor could be a promising novel way to affect risk of breast cancer progression. Table S1. DrugATC-code Enalapril C09AA02 ,

Ovarian cancer (OC) has a poor prognosis. Hypertension may be a prognostic factor for OC, but it is unclear whether antihypertensive (anti-HT) drug use of modifies OC prognosis. We performed a population-based analysis assessing the effect of anti-HT drug use on OC mortality. A cohort of 12,122 women identified from the Finnish Cancer Registry with OC in 1995–2013 was combined with information on their anti-HT drug use during the same time period. Use of each anti-HT drug was analysed as a time-dependent variable. Analyses were run for five, ten and full follow-up (19-year) mortality with cardiovascular morbidity risk evaluated in competing risk analysis. No anti-HT drug group was associated with OC survival within five years after OC diagnosis. At ten years, a dose-dependent association was observed between pre-diagnostic ACE-inhibitor use and improved OC survival. With full follow-up, post-diagnostic high-intensity use associated with reduced OC death risk for multiple anti-HT drug groups. In competing risk analysis, only the post-diagnostic use of ACE-inhibitors associated with increased OC survival. Anti-HT drugs were not associated with survival benefits within five years after OC diagnosis. ACE-inhibitors may confer survival benefits in women with OC, but further confirmatory studies are needed.

Introduction:To analyse the association between antihypertensive (anti-HT) drug use and risk of urothelial cancer (UC) death. UC occur as bladder cancer (BCa) and upper tract urothelial carcinomas (UTUCs). Hypertension is a suggested risk factor for BCa and may impair disease prognosis. However it`s unclear if use of anti-HT drugs could improve prognosis of UC. Materials and Methods:We evaluated the association between use of anti-HT drugs and UC survival among 14,065 participants diagnosed with BCa and 1080 with UTUC during 1995-2012 in Finland. We analyzed data using multivariable adjusted conditional Cox regression model.Results: Angiotensin-receptor (ATR) blocker use before BCa diagnosis was associated with slightly decreased risk of BCa death (HR: 0.81 CI: 0.71-0.93). The association was dose-dependent and it decreased in association with elevated intensity of ATR-blocker use.Post-diagnostic use of ATR-blockers was similarly associated with better survival compared to nonusers (HR: 0.81 CI: 0.71-0.92. Interestingly use of calcium-channel blockers associated also with better survival and the risk of BCa death decreased with increasing intensity of use (HR: 0.67 CI: 0.52-0.86 for highest intensity). Conclusions:Our large population-based cohort suggests decreased risk of BCa death among ATRblocker and calcium-channel blocker users. The risk association among ATR-blockers and calciumchannel blockers was dose-dependent suggesting a causal explanation. Similar risk associations are not observed for other anti-HT drug users which may suggest a direct effect of ATR blocker or calcium-channel blocker use. Further studies are needed to elucidate the potential anticancer mechanism.

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