Statins and the risk of pancreatic cancer in Type 2 diabetic patients—A population‐based cohort study

The aim of this study was to determine whether statin use exerts a protective effect against pancreatic cancer in Type 2 diabetic patients. A retrospective population‐based cohort study was designed to analyze the National Health Insurance Research database (NHIRD) from 1997–2010 in Taiwan. A total of 1,140,617 patients with a first‐time diagnosis of Type 2 diabetes were enrolled. The event was defined as newly diagnosed pancreatic cancer. A Cox proportional hazards regression model with time‐dependent covariates was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of pancreatic cancer associated with statin use in the diabetic cohort. A total of 2,341 patients with newly diagnosed pancreatic cancer were identified in the diabetic cohort during the follow‐up period of 6,968,217.1 person‐years. In this cohort, 450,282 patients were defined as statin users (statin use ≥28 cumulative defined daily dose [cDDD] in 1 year) and 0.14% had pancreatic cancer; 690,335 patients were statin nonusers (statin use <28 cDDD in 1 year) and 0.25% had pancreatic cancer. Statin use significantly decreased the risk of pancreatic cancer (adjusted HRs: 0.78 in 28–83 cDDD per year; 0.48 in 84–180 cDDD per year; and 0.33 in >180 cDDD per year) after adjusting for multiple confounders. There was a significant dose‐effect of statin use for the risk of pancreatic cancer (p for trend: <0.001). Statin use may be associated with a reduced risk of pancreatic cancer in Type 2 diabetic patients. More research is needed to clarify this association.     

Prospective analysis of association between statins and pancreatic cancer risk in the Women’s Health Initiative

Purpose

To determine whether HMG-CoA reductase inhibitors (statins) are associated with a lower risk of pancreatic cancer.

Methods

The population included 160,578 postmenopausal women enrolled in the Women’s Health Initiative (WHI) in which 385 incident cases of pancreatic cancer were identified over an average of 8.69 (SD ±4.59) years. All diagnoses were confirmed by medical record and pathology review. Information on statin use and other risk factors was collected at baseline and during follow-up. Multivariable-adjusted hazards ratios (HRs) and 95 % confidence intervals (CIs) evaluating the relationship between prior statin use (at baseline only as well as in a time-dependent manner) and risk of pancreatic cancer were computed from Cox proportional hazards regression analyses after adjusting for appropriate confounders. We also evaluated the effect of statin type, potency, lipophilic status, and duration of use. All statistical tests were two-sided.

Results

Statins were used at baseline by 12,243 (7.5 %) women. The annualized rate of pancreatic cancer in statin users and nonusers, respectively, was 0.0298 versus 0.0271 %. The multivariable-adjusted HR for statin users versus nonusers at baseline was 0.92 and 95 % CI 0.57–1.48. In a time-dependent model, the HR for low-potency statins was 0.46, 95 % CI 0.20–1.04. There was no significant effect seen by statin lipophilicity or duration of use.

Conclusions

There was no significant relationship between statins and pancreatic cancer risk in the WHI; however, there was a marginal inverse association noted for low-potency statins. Analyses of larger numbers of cases are needed to further explore this relationship.

     

Statin use and risk of liver cancer: Evidence from two population-based studies

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case–control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self-reported statin use and cancer-registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case–control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43–0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24–0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45–2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.     

Prospective analysis of association between use of statins and melanoma risk in the Women's Health Initiative

BACKGROUND:

Melanoma is the most lethal form of skin cancer, with an estimated 68,130 new cases and 8700 deaths in the United States in 2010. The increasing incidence and high death rate associated with metastatic disease support the need to focus on prevention. The authors used data from the Women's Health Initiative (WHI) to assess whether 3‐hydroxy‐3 methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of melanoma.

METHODS:

The study population consisted of 119,726 postmenopausal white women, in which 1099 cases of malignant melanoma were identified over an average (±standard deviation) of 11.6 ± 3.2 years. All diagnoses were confirmed by medical record review and pathology reports. Information on statin use was collected at baseline and during follow‐up. Self‐administered and interview‐administered questionnaires were used to collect information on other risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses investigated the association of any statin use, type, potency, lipophilic status, and duration of use with melanoma.

RESULTS:

Statins were used by 8824 women (7.4%) at baseline. The annualized rate of melanoma was 0.09% among statin users and 0.09% among nonusers The multivariable adjusted HR for statin users compared with nonusers was 1.14 (95% CI, 0.91‐1.43). There were no significant differences in risk based on statin type, potency, category, duration, or in time‐dependent models.

CONCLUSIONS:

There was no significant association between statin use and melanoma risk among postmenopausal women in the WHI. Cancer 2012. © 2012 American Cancer Society.     

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.     

Incidence of interstitial pneumonitis among breast cancer patients: a 10-year Danish population-based cohort study

Chemotherapy and radiation therapy may increase risk for interstitial pneumonitis (IP) in breast cancer patients, but there are little current population-based data on IP incidence in these patients. We assessed population-based incidence rates (IRs) of IP among Danish breast cancer patients and compared these with IRs for the Danish general population. Through the Danish Cancer Registry, we identified all Danish breast cancer patients (n=35 823) diagnosed between 1994 and 2004. Treatment data were obtained from the Danish Breast Cancer Cooperation Group database, and data on IP, from the Danish National Registry of Patients. We computed IRs of IP among breast cancer patients and age-standardised incidence rate ratios (SIRs) comparing breast cancer patients with the general population. During follow-up, 28 breast cancer patients were registered with an IP diagnosis (IR=17.3 per 100,000 person-years (p-y) (95% confidence intervals (95% CI): 11.7-24.6)). When follow-up was restricted to 1 year after the first breast cancer diagnosis, eight patients with IP were identified (IR=23.4 per 100,000 p-y (95% CI: 11.0-44.1)). The SIR comparing breast cancer patients with the general population was 8.4 (95% CI: 5.7-11.9). Thus, although IP is a rare adverse event among breast cancer patients, its risk is substantially higher than that in the general population.     

Estrogen replacement therapy and breast cancer survival in a large screening study

BACKGROUND: Hormone replacement therapy has been associated in some studies with reductions in breast cancer mortality among women who develop this disease. It is unclear whether this association reflects the biologic activity of the hormones or the earlier detection of tumors among hormone users. We examined breast cancer mortality among women who were diagnosed with axillary lymph node-negative and node-positive breast cancer according to the currency of estrogen use at diagnosis. METHODS: Vital status through June 1995 was determined for 2614 patients with postmenopausal breast cancer diagnosed during the period from 1973 to January 1981. We estimated adjusted hazard-rate ratios (adjusting for tumor size, age, race, Quetelet [body mass] index, and number of positive lymph nodes in women with node-positive disease) and unadjusted cumulative probabilities of breast cancer death over time since diagnosis. RESULTS: Among patients with node-negative disease, rate ratios for breast cancer mortality associated with current use compared with nonuse at diagnosis were 0.5 (95% confidence interval [CI] = 0.3-0.8) until 144 months after diagnosis and 2.2 (95% CI = 0.9-5.2) thereafter. Mortality was not statistically significantly lower in past users. The cumulative probabilities of breast cancer mortality at the end of follow-up were 0.14, 0.14, and 0.09 in nonusers, past users, and current users, respectively. Among women with node-positive disease, the rate ratios associated with current and past use were both 0.5 until 48 months after diagnosis (95% CI = 0.3-0.8 for current users; 95% CI = 0.3-0.9 for past users) and were 1.1 (95% CI = 0.7-1.7) and 1.8 (95% CI = 1.2-2.7), respectively, thereafter. The cumulative probabilities of breast cancer mortality were 0.32, 0.39, and 0.27 in nonusers, past users, and current users, respectively. CONCLUSIONS: Patients with breast cancer who were using replacement estrogens at the time of diagnosis experienced reductions in breast cancer mortality, which waned with the time since diagnosis.     

High Receipt of Statins Reduces the Risk of Lung Cancer in Current Smokers With Hypercholesterolemia: The National Health Insurance Service–Health Screening Cohort

BackgroundThe incidence and mortality of lung cancer have risen steadily with the increasing popularity of tobacco smoking. Observational studies suggest that statins, which are widely used to lower cholesterol, may prevent lung cancer; however, other studies have produced conflicting results. We investigated the effect of statin receipt on lung cancer risk in Korean men according to smoking status.Patients and MethodsWe collected data from the 2002-2015 National Health Insurance Service–National Health Screening Cohort (NHIS-HEALS). We included a total of 16,588 men in the final analysis. We classified the participants as having high or low statin receipt or as not receiving statins. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer risk by statin receipt after adjusting for potential confounders.ResultsWe identified 363 patients with a new diagnosis of lung cancer from 2005 to 2015. Compared to participants who did not receive statins, high statin receipt resulted in a reduced lung cancer risk (HR = 0.64; 95% CI, 0.47, 0.85) after adjustment for confounders. Among current smokers, the fully adjusted HR for high statin receipt compared to those who did not receive statin therapy was 0.50 (95% CI, 0.32, 0.79).ConclusionHigh statin receipt was associated with lower risk of lung cancer in Korean men with hypercholesterolemia, especially current smokers.     

Chronic therapy with selective serotonin reuptake inhibitors and survival in newly diagnosed cancer patients

Depression might be associated with shorter disease specific survival. Selective serotonin reuptake inhibitors (SSRIs) were previously reported to increase the risk of certain malignancies. We aimed to evaluate the impact of SSRIs on cancer mortality. Five retrospective cohort studies were conducted in a UK population‐representative database that included all individuals with an incident diagnosis of melanoma, breast, prostate lung and colorectal cancer. The primary exposure of interest was continuous use of SSRIs with past use as the comparison reference. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). The study included 5,591 newly diagnosed cancer patients. Continuous SSRI use was associated with lower survival compared to past users for melanoma, breast, prostate, lung and colorectal cancers with HRs for the risk of death of 2.02 (95% CI 1.24–3.28), 1.91 (95% CI 1.53–2.38), 1.79 (95% CI 1.38–2.33), 1.44 (95% CI 1.19–1.75) and 1.51 (95% CI 1.21–1.72) respectively. The incidence of death during the first 2 years following cancer diagnosis associated with continuous SSRI use were elevated for breast (1.72, 95% CI 1.30–2.27), prostate (1.64, 95% CI 1.20–2.24) and lung cancers (1.45, 95% CI 1.26–1.66). In conclusion, continuous use of SSRIs might be associated with lower survival in cancer patients.     

Breast cancer recurrence,bone metastases,and visceral metastases in women with stage II and III breast cancer in Denmark

Purpose

We developed and validated algorithms to identify metastases and breast cancer recurrence in Danish medical registries. We computed the incidence rate (IR) and hazard ratios (HRs) to evaluate predictors of these outcomes in stage II/III breast cancer patients.

Methods

We included all women in Denmark diagnosed during 1999–2011 with regional or stage II/III breast cancer. Demographic, tumor, and treatment data were ascertained from population-based health registries. To facilitate diagnostic work-up of the primary cancer, follow-up began 180 days after diagnosis and continued until recurrence/metastases, death, or 31 December 2012, whichever occurred first. We computed the positive predictive values (PPVs) of recurrence, bone metastases, and visceral metastases using medical records as a gold standard. We calculated the cumulative incidence, IR per 10,000 person years, and used Cox regression to compute the HRs and associated 95% confidence intervals (95% CI) for each outcome.

Results

Among 23,478 patients, 7073 had regional stage and 16,405 had stage II/III breast cancer. The PPV for recurrence was 72.6% (95% CI 59.3, 83.3%). The PPVs for bone and visceral metastases were 92.3% (95% CI 69.3–99.2%) and 70.8% (95% CI 51.1, 85.9%), but had low sensitivity. Five-year cumulative incidence of recurrence, bone metastases, and visceral metastases were 18.4, 2.2, and 5.2%, with corresponding 5-year IRs of 540 (95% CI 524, 557), 60 (95% CI 55, 65), and 144 (95% CI 136, 152), respectively. Predictors of recurrence and metastases included age, stage, hormone receptor status, and cancer treatment.

Conclusion

Our algorithms show moderate to high PPVs for recurrence and metastases. The IRs of metastases were lower compared with other registry-based cohort studies, so may be underestimated in Danish registries.

     

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.     

Impact of comorbidity on mortality: a cohort study of 62,591 Danish women diagnosed with early breast cancer, 1990-2008

The incidence of breast cancer, as well as other chronic disease, increases with age, older breast cancer patients being more likely than younger to suffer from other diseases at time of diagnosis. Our objective was to assess the effect of comorbidity on mortality after early breast cancer. 62,591 women diagnosed with early breast cancer 1990–2008 were identified using the Danish Breast Cancer Cooperative Group Registry. Data were linked to the Danish National Patient Register and the Danish Register of Causes of Death. Main outcome measures were mortality from all causes, breast cancer, and non-breast cancer causes in relation to Charlson comorbidity index (CCI). Compared with patients without comorbidity (CCI 0), the presence of comorbidity increased the risk of dying from breast cancer as well as other causes with adjusted hazard ratios (HRs) for all-cause mortality of 1.45 (CI 95% 1.40–1.51) for CCI 1, 1.52 (95% CI 1.45–1.60) for CCI 2, and 2.21 (95% CI 2.08–2.35) for CCI 3+. Equivalent HRs for breast cancer-specific mortality were 1.30 (95% CI, 1.24–1.36) for CCI 1, 1.31 (95% CI 1.23–1.39) for CCI 2, and 1.79 (95% CI, 1.66–1.93) for CCI 3+ (all P values < 0.0001). For patients with CCI 0, 5-year overall survival increased over time from 72.5% (95% CI, 71.7–73.3%) in 1990–1994 to 81.6% (95% CI, 80.9–82.2) in 2000–2004, whereas the 5-year overall survival remained stable around 43% among the patients with CCI 3+. This population-based cohort study shows that compared with patients without comorbidity, the risk of dying from breast cancer as well as other causes increased significantly with increasing CCI score. While survival improved over time for patients without comorbidity, no improvement was seen among patients with severe comorbidity (CCI 3+).     

Use of acetochlor and cancer incidence in the Agricultural Health Study

Since its registration in 1994 acetochlor has become a commonly used herbicide in the US, yet no epidemiologic study has evaluated its carcinogenicity in humans. We evaluated the use of acetochlor and cancer incidence among licensed pesticide applicators in the Agricultural Health Study. In telephone interviews administered during 1999–2005, participants provided information on acetochlor use, use of other pesticides and additional potential confounders. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (95% CI) for cancers that occurred from the time of interview through 2011 in Iowa and 2010 in North Carolina. Among 33,484 men, there were 4,026 applicators who used acetochlor and 3,234 incident cancers, with 304 acetochlor‐exposed cases. Increased risk of lung cancer was observed among acetochlor users (RR = 1.74; 95% CI: 1.07–2.84) compared to nonusers, and among individuals who reported using acetochlor/atrazine product mixtures (RR = 2.33; 95% CI: 1.30–4.17), compared to nonusers of acetochlor. Colorectal cancer risk was significantly elevated among the highest category of acetochlor users (RR = 1.75; 95% CI: 1.08–2.83) compared to never users. Additionally, borderline significantly increased risk of melanoma (RR = 1.61; 95% CI: 0.98–2.66) and pancreatic cancer (RR = 2.36; 95% CI: 0.98–5.65) were observed among acetochlor users. The associations between acetochlor use and lung cancer, colorectal cancer, melanoma and pancreatic cancer are suggestive, however the lack of exposure‐response trends, small number of exposed cases and relatively short time between acetochlor use and cancer development prohibit definitive conclusions.