Statin use and breast cancer risk in a large population-based setting.

BACKGROUND: Mechanistic studies suggest that 3-hydroxy-3-methylglutaryl CoA inhibitors (statins) reduce the risk of breast cancer. Observational studies offer mixed results. METHODS: To evaluate the relation between statin use and breast cancer risk, we conducted a cohort study among women ages 45 to 89 years within an integrated health care delivery system. Information on statin use and covariates were obtained from automated databases. We identified breast cancer cases through the Surveillance, Epidemiology, and End Results registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for invasive breast cancer among statin users compared with nonusers. RESULTS: Among 92,788 women studied from 1990 to 2004, median follow-up time was 6.4 years, and 2,707 breast cancer cases were identified. During the study period, 7.4% of women used statins for at least 1 year, and the median duration of use was 3.1 years. We found no difference in breast cancer risk among statin users (HR, 1.07; 95% CI, 0.88-1.29) compared with nonusers. Risk of breast cancer did not differ by duration of use (1-2.9, 3-4.9, or >or=5 years) or hydrophobic statin use. We found a suggestive increased risk of breast cancer among statin users of >or=5 years (HR, 1.27; 95% CI, 0.89-1.81 for any statins and HR, 1.47; 95% CI, 0.89-2.44 for hydrophobic statins) and of estrogen receptor-negative tumors with increasing duration of statin use (1-2.9 years: HR, 1.33; 95% CI, 0.64-2.77; 3-4.9 years: HR, 1.68; 95% CI, 0.72-3.92; >or=5 years: HR, 1.81; 95% CI, 0.75-4.36). CONCLUSION: This study does not support an association between statin use and breast cancer risk.     

Prostate cancer risk among users of finasteride and alpha-blockers - a population based case-control study

Finasteride has been reported to reduce prostate cancer risk in asymptomatic men. However, in clinical practice finasteride and alpha-blockers are used to treat benign prostatic hyperplasia (BPH). We evaluated prostate cancer risk among users of BPH pharmacotherapy at the population level. Comprehensive Finnish national registries provided information on 24723 prostate cancer cases and controls. Overall, prostate cancer risk was elevated among users of both drug categories compared to non-users (odds ratio, OR=1.41; 95% confidence interval, CI 1.31-1.51 for finasteride and OR=1.79; 95% CI 1.67-1.91 for alpha-blockers). However, the risk was lower among finasteride users when compared with alpha-blocker users (OR=0.80; 95% CI 0.64-1.00). Regular finasteride users had the lowest risk. The increased risk is probably due to enhanced diagnostics of prostate cancer in men with BPH. Finasteride use does not decrease prostate cancer incidence compared with non-users. Nevertheless, the risk is lower when compared with alpha-blocker users.     

Statin use and female reproductive organ cancer risk in a large population-based setting

Objective  Statins are an effective and commonly used cholesterol-lowering medication class, but their hypothesized effects on cancer risk remain uncertain. We evaluated the association between statin use and endometrial as well as ovarian cancer risks. Methods  We conducted a retrospective study with two cohorts of women aged 45–89 years during 1990–2004 within an integrated healthcare delivery system. Information on statin use and covariates were obtained from automated databases. We identified cancer cases through the Surveillance, Epidemiology, and End Results registry. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident invasive endometrial and ovarian cancers among statin users compared to nonusers. Results  Women were followed for a median of about six years. Among 73,336 women studied, 568 endometrial cancer cases were identified. During the study period, 6% of women used statins for at least one year and the median duration of use was 3.1 years. Although not statistically significant, we found a reduction in endometrial cancer risk among statin users (HR = 0.67; 95% CI: 0.39–1.17) compared to nonusers. We identified 326 ovarian cancer cases in a cohort of 93,619 women. There was also a nonsignificant decrease in ovarian cancer risk among statin users (HR = 0.69; 95% CI: 0.32–1.49). Conclusion  Our study does not support an association between statin use and endometrial as well as ovarian cancers, but a reduced risk cannot be ruled out.     

Statin medication use and the risk of biochemical recurrence after radical prostatectomy

BACKGROUND:

Although controversial, evidence suggests statins may reduce the risk of advanced prostate cancer (PC), and recently statin use was associated with prostate‐specific antigen (PSA) reductions among men without PC. The authors sought to examine the association between statin use and PSA recurrence after radical prostatectomy (RP).

METHODS:

The authors examined 1319 men treated with RP from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Time to PSA recurrence was compared between users and nonusers of statin at surgery using Cox proportional hazards models adjusted for multiple clinical and pathological features.

RESULTS:

In total, 236 (18%) men were taking statins at RP. Median follow‐up was 24 months for statin users and 38 for nonusers. Statin users were older (P < .001) and underwent RP more recently (P < .001). Statin users were diagnosed at lower clinical stages (P = .009) and with lower PSA levels (P = .04). However, statin users tended to have higher biopsy Gleason scores (P = .002). After adjusting for multiple clinical and pathological factors, statin use was associated with a 30% lower risk of PSA recurrence (hazard ratio “HR”, 0.70; 95% confidence interval “CI”, 0.50‐0.97; P = .03), which was dose dependent (relative to no statin use; dose equivalent<simvastatin 20 mg: HR, 1.08; 95% CI, 0.66‐1.73; P = .78; dose equivalent = simvastatin 20 mg: HR, 0.57; 95% CI, 0.32‐1.00; P = .05; dose equivalent>simvastatin 20 mg: HR, 0.50; 95% CI, 0.27‐0.93; P = .03).

CONCLUSIONS:

In this cohort of men undergoing RP, statin use was associated with a dose‐dependent reduction in the risk of biochemical recurrence. If confirmed in other studies, these findings suggest statins may slow PC progression after RP. Cancer 2010. © 2010 American Cancer Society.     

Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort

HMG-coA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use. However, little is known about the association between long-term statin use and incidence of most types of cancers. We examined the association between long-term use of cholesterol-lowering drugs, predominantly statins, and the incidence of ten common cancers, as well as overall cancer incidence, among 133,255 participants (60,059 men and 73,196 women) in the Cancer Prevention Study II Nutrition Cohort during the period from 1997 to 2007. Multivariate Cox proportional hazards regression was used to estimate relative risks (RR). Current use status and duration of use were updated during follow-up using information from biennial follow-up questionnaires. Current use of cholesterol-lowering drugs for five or more years was not associated with overall cancer incidence (RR = 0.97, 95% CI = 0.92-1.03), or incidence of prostate, breast, colorectal, lung, bladder, renal cell, or pancreatic cancer but was associated with lower risk of melanoma (RR = 0.79, 95% CI = 0.66-0.96), endometrial cancer (RR = 0.65, 95% CI = 0.45-0.94), and non-Hodgkin lymphoma (NHL; RR = 0.74, 95% CI = 0.62-0.89). These results suggest that long-term use of statins is unlikely to substantially increase or decrease overall cancer risk. However, associations between long-term statin use and risk of endometrial cancer, melanoma, and NHL deserve further investigation.     

Statin use and the risk of prostate cancer: A metaanalysis of 6 randomized clinical trials and 13 observational studies

Statins have been suggested to prevent prostate cancer. Our aim was to examine statin use in relation to both total prostate cancer and the more clinically important advanced prostate cancer, through a detailed metaanalysis of the epidemiologic studies published on the subject in peer-reviewed literature. A comprehensive search for articles published up to November 2007 was performed, reviews of each study were conducted and data were abstracted. Prior to metaanalysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup and sensitivity analyses were also performed. Nineteen studies [6 randomized clinical trials (RCTs), 6 cohort and 7 case-control studies] contributed to the analysis. There was no evidence of an association between statin use and total prostate cancer among either RCTs (RR = 1.06, 95% CI: 0.93-1.20) or the observational studies (RR = 0.89, 95% CI: 0.65-1.24). However, high heterogeneity was detected among the observational studies. Moreover, long-term statin use did not significantly affect the risk of total prostate cancer (RR = 0.93, 95% CI: 0.77-1.13). In contrast, synthesis of the available reports that had specifically examined statin use in relation to advanced prostate cancer indicated a protective association (RR = 0.77, 95% CI: 0.64-0.93). Our results do not support the hypothesis that statins reduce the risk of total prostate cancer. However, further research is required to investigate whether the particular association of statin use with lower risk of advanced prostate cancer is indeed causal.     

Prospective study of Type 2 diabetes mellitus,anti‐diabetic drugs and risk of prostate cancer

Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti‐diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82–0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77–1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55–0.98), compared to men with T2DM not on anti‐diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95–1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.     

Long-term aspirin use and the risk of total, high-grade, regionally advanced and lethal prostate cancer in a prospective cohort of health professionals, 1988-2006

Experimental studies suggest a role for aspirin in the chemoprevention of prostate cancer and epidemiological evidence supports a modest inverse association between regular aspirin use and prostate cancer risk, especially for advanced disease. In a prospective cohort study of 51,529 health professionals aged 40-75 years at baseline, we evaluated long-term aspirin use and the incidence of total, high-grade (Gleason 8-10, n = 488), regionally advanced (T3b-T4 or N1, n = 228) and lethal prostate cancer (M1, bony metastases or prostate cancer death, n = 580) from 1988-2006. We used Cox proportional hazards regression to evaluate risk associated with frequency (days/week), quantity (tablets/week), recency and duration of aspirin use after multivariable adjustment for confounders and other predictors of prostate cancer risk. A total of 4,858 men were diagnosed with prostate cancer during the 18-year study period. Men taking ≥ 2 adult-strength aspirin tablets a week had a 10% lower risk of prostate cancer (p-for-trend = 0.02). For regionally advanced cancer, we observed no significant associations with aspirin use. For high-grade and lethal disease, men taking ≥ 6 adult-strength tablets/week experienced similar reductions in risk hazard ratio [HR = 0.72 (95% confidence intervals [CI]: 0.54, 0.96) and HR = 0.71 (95% CI: 0.50, 1.00)]. Analytical approaches to address bias from more frequent prostate-specific antigen screening among aspirin users did not yield different conclusions. We observed reductions in the risk of high-grade and lethal prostate cancer associated with higher doses of aspirin, but not with greater frequency or duration, in a large, prospective cohort of health professionals. Our data support earlier observations of modest inverse associations with advanced prostate cancer.     

Recreational Physical Activity and Prostate Cancer Risk (United States)

Objective To examine recreational physical activity (PA) and prostate cancer risk in a large cohort of men living in Washington State, focusing on frequency and type of physical activity at various times throughout life. Methods In a prospective cohort study, we assessed physical activity in 34,757 men (50–76 years at baseline) using a questionnaire. Men were recruited into the study between 2000 and 2002. Five hundred and eighty-three men developed prostate cancer. Results Using Cox proportional hazards regression, PA either in the 10 years before baseline or earlier in life was not associated with prostate cancer risk. However, compared to no activity, ≥10.5 MET-h per week (the median level) of PA was associated with a reduced prostate cancer risk among men who were normal weight (HR = 0.69, 95% CI 0.46–1.0), ≥65 years at diagnosis (HR = 0.75, 95% CI 0.55–1.0) and who had not had a recent PSA (HR = 0.47, 95% CI 0.28–0.81). Greater PA was associated with an increased risk among men who were obese (HR = 1.5, 95% CI 0.95–2.4), and no association among men <65 years or with a recent history of PSA screening (all p for interactions ≤0.02). Conclusions PA was not associated with prostate cancer risk, except in subgroups defined by age, obesity, and screening history.     

Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors

PURPOSE: We examined the association between post-diagnosis statin use (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] inhibitors) and risk of breast cancer recurrence. MATERIALS AND METHODS: The study included 1945 early stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study. Women who were diagnosed from 1997 to 2000 and identified from the Kaiser Permanente Northern California (KPNC) Cancer Registry entered the cohort on average 2 years post-diagnosis. Information on statin use was obtained from the KPNC pharmacy database. A total of 210 breast cancer recurrences were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). RESULTS: The mean duration of statin use in the cohort among those who initiated use post-diagnosis was 1.96 years, and lipophilic statins were mainly used (97.8%). Starting statins after diagnosis was suggestive of a decreased risk of breast cancer recurrence (RR = 0.67; 95% CI: 0.39-1.13). Risk of recurrence decreased with increasing duration of statin use after diagnosis (p linear trend = 0.02). CONCLUSION: Our findings provide initial support for an inverse association between post-diagnosis, lipophilic statin use and risk of breast cancer recurrence.     

Use of statins and risk of glioma: a nationwide case–control study in Denmark

Background:

Laboratory studies and a single case–control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting.

Methods:

We conducted a nationwide case–control study in Denmark based on population-based medical registries. We identified all patients aged 20 to 85 years with a first diagnosis of histologically verified glioma during 2000–2009. These cases were matched on birth year and sex with population controls. Prior use of statins since 1995 was classified into short-term use (<5 years) and long-term use (5+ years). We used conditional logistic regression to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with statin use, adjusted for potential confounders.

Results:

A total of 2656 cases and 18 480 controls were included in the study. The risk of glioma was reduced among long-term statin users (OR=0.76; 95% CI: 0.59–0.98) compared with never users of statins, and was inversely related to the intensity of statin treatment among users (OR=0.71; 95% CI: 0.44–1.15 for highest intensity). The inverse association between long-term statin treatment and glioma risk was more pronounced among men aged ⩽60 years (OR=0.40; 95% CI: 0.17–0.91) compared with men aged 60+ years (OR=0.71; 95% CI: 0.49–1.03). An inverse association was also observed among women aged ⩽60 years (OR=0.28; 95% CI: 0.06–1.25), but not among women over age 60 years (OR=1.23; 95% CI: 0.82–1.85).

Conclusion:

Long-term statin use may reduce the risk of glioma.     

Use of multivitamins and prostate cancer mortality in a large cohort of US men

Objective: To assess the association between the use of multivitamins and prostate cancer mortality.Methods: A total of 5585 deaths from prostate cancer were identified during 18 years of follow-up of 475,726 men who were cancer-free and provided complete information on multivitamin use at enrollment in the Cancer Prevention Study II (CPS-II) cohort in 1982. Cox proportional hazards modeling was used to measure the association between multivitamin use at baseline and death from prostate cancer and to adjust for potential confounders.Results: The death rate from prostate cancer was marginally higher among men who took multivitamins regularly (≥15 times/month) compared to non-users (multivariate rate ratio=1.07, 95% CI: 0.99–1.15); this risk was statistically significant only for those multivitamin users who used no additional (vitamin A, C, or E) supplements (multivariate rate ratio=1.15, 95% CI: 1.05–1.26). In addition, risk was greatest during the initial four years of follow-up (1982–1986, multivariate rate ratio=1.12, 95 CI: 0.87–1.46).Conclusions: Regular multivitamin use was associated with a small increase in prostate cancer death rates in our study, and this association was limited to a subgroup of users.     

Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. cohort.

BACKGROUND: 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Long-duration statin use was associated with substantially reduced risk of advanced prostate cancer in a recent large prospective study. METHODS: We examined the association between use of cholesterol-lowering drugs and prostate cancer incidence by disease stage and grade among 55,454 men in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate RRs. RESULTS: During follow-up from 1997 to 2003, we identified 3,413 cases of incident prostate cancer, including 317 cases of advanced prostate cancer. After adjustment for age, history of prostate-specific antigen testing, and other potential prostate cancer risk factors, current use of cholesterol-lowering drugs for 5 or more years was not associated with overall prostate cancer incidence (multivariate adjusted rate ratio, 1.06; 95% confidence interval, 0.93-1.20), but was associated with a marginally statistically significant reduction in risk of advanced prostate cancer (rate ratio, 0.60; 95% confidence interval, 0.36-1.00). CONCLUSION: These results provide some support for the hypothesis that long-term statin use is associated with reduced risk of advanced prostate cancer.