Statin use and fatal prostate cancer: a matched case-control study

BACKGROUND:

Statins are some of the most commonly prescribed medications in medical practice, and prostate cancer is the most common malignancy among men. Although there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study to date has specifically examined statin use and prostate cancer mortality. The authors conducted this population‐based case‐control investigation to examine this association.

METHODS:

This was a matched case‐control study. Cases were residents of New Jersey ages 55 to 79 years who died from prostate cancer between 1997 and 2000. The cases were matched individually to population‐based controls by 5‐year age group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. Conditional logistic regression was used to adjust for confounders.

RESULTS:

In total, 718 cases were identified, and cooperation was obtained from 77% of their spouses (N = 553). After a review of medical records, 387 men were eligible, and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% confidence interval, 0.34‐0.70) and decreased to 0.37 (P < .0001) after adjusting for education, waist size, body mass index, comorbidities, and antihypertensive medication. There was little difference between lipophilic and hydrophilic statins, but more risk reduction was noted for high‐potency statins (73%; P < .0001) compared with low‐potency statins (31%; P = .32).

CONCLUSIONS:

Statin use was associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer. Cancer 2012. © 2011 American Cancer Society.     

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

One in five cancers in women is diagnosed prior to and during a woman's fertile years. Our study evaluates mortality risks in offspring of mothers with history of cancer. From the Swedish Multi‐generation Register and the Cancer Register, we identified all 174,893 children whose mother had been diagnosed with cancer between 1958 and 2001. We categorized offspring into those born before (>1 year before), around (within 1 year before and after diagnosis) and after (>1 year after) their mother's cancer diagnosis and compared their risks of death (standardized mortality ratios, SMRs) and causes of death to the background population. Overall, offspring of mothers diagnosed with cancer had no increased mortality risk (SMR, 1.00; 95% confidence interval [CI], 0.97–1.03). Increased mortality risks were found in offspring of mothers with tobacco‐related cancers (head and neck, thoracic and cervical) (SMR, 1.23; 95% CI, 1.13–1.33), in children born around their mother's diagnosis (SMR, 1.66; 95% CI, 1.25–2.13) and in children born after their mother's hematopoietic cancer diagnosis (SMR, 2.07; 95% CI, 1.10–3.35). Compared to the background population, children born around their mother's diagnosis were more likely to die of congenital and perinatal conditions. Overall, offspring of women diagnosed with cancer were not at increased risk of death, except for certain subgroups. Timing of pregnancy in relation to diagnosis and cancer site modifies mortality risks in the offspring.     

Examining stage IIB survival in a population‐based cohort of patients with colorectal cancer

BACKGROUND:

In Nova Scotia, Canada, a previous study of colorectal cancer (CRC) cases diagnosed between January 1, 2001, and December 31, 2005, found that patients with stage IIB CRC had similar 5‐year overall survival (OS) to those with stage IIIC cancer. This study sought to examine factors contributing to the observed stage IIB outcome, specifically nodal harvest, receipt of chemotherapy, and use of a new coding system to derive stage.

METHODS:

The provincial cancer registry identified all CRC cases diagnosed during the study period and staged this cohort using the Collaborative Stage (CS) Data Collection System. All patients with stage II and III cancer in the cohort were examined. Kaplan‐Meier (KM) survival curves compared 5‐year OS for patients with stage IIB cancer based on the factors of interest, and compared patients with stage IIB cancer to those with stage IIA and III cancer.

RESULTS:

OS for patients with stage IIB cancer (n = 187) was 44.7%, and differed depending on adequacy of nodal harvest (P = .005) and whether pathological or clinical/mixed evidence was used to derive stage (P = .013). Pathologically‐staged patients with stage IIB cancer who had adequate nodal harvest had marginally improved OS compared to pathologically‐staged patients who had inadequate nodal harvest (P = .07), and improved survival compared to patients with clinical/mixed stage (P = .004). Pathologically‐staged patients with stage IIB cancer with adequate nodal harvest demonstrated similar 5‐year OS to those with stage IIA and III cancer (P = .52 and P = .25, respectively). Cox proportional hazards models supported these findings.

CONCLUSIONS:

The inclusion of clinical/mixed evidence into staging classification and, perhaps to a lesser extent, the adequacy of nodal harvest appear to contribute to the observed worse survival for patients with stage IIB versus stage III cancer. Cancer 2012. © 2012 American Cancer Society.     

Late mortality among 5‐year survivors of early onset cancer: A population‐based register study

To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation‐wide population‐based registry study provides information concerning cause‐specific long‐term mortality among 16,769 5‐year survivors of early onset cancer (aged 0–34 years at diagnosis), with follow‐up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6‐fold, (95% CI 4.4–4.8). Highest SMRs were found for malignancies (12.8, 95% CI 12.3–13.3), infectious (4.8, 95%CI 2.9–6.7) and cardiovascular diseases (1.9, 95% CI 1.7–2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non‐malignancy‐related mortality was due to cardiovascular disease with a steady rise throughout the follow‐up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancy‐related mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non‐malignancy‐related mortality stress the need to set up long‐term individual follow‐up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those.     

Association between tubal ligation and endometrial cancer risk: A Swedish population‐based cohort study

Tubal ligation results in less advanced stages and lower risk of metastatic spread at diagnosis of endometrial cancer (EC) but the primary preventive effect of the procedure is unclear. In a Swedish nationwide population‐based cohort study, we crosslinked registry data for tubal ligation, EC, and death for Swedish women between 1973 and 2010. All women were followed until EC, emigration, hysterectomy for non‐cancerous reasons, death, or end of follow‐up. Primary outcome was incidence of EC and secondary outcome overall survival. We calculated adjusted incidence rates (IR) per 100,000 person‐years and hazard ratios (HR) using Cox regression models. A total of 35,711 cases of EC were identified among 5,385,186 women. The IR of EC among exposed was 17.7 (95% CI 15.7–19.9) versus 29.0 (95% CI 28.7–29.3) among unexposed (per 100,000 women years). Exposed individuals had significantly reduced risk of EC (HR 0.73, 95% CI 0.65–0.83). The mortality rate among women with EC was 72% lower in exposed compared to unexposed (IR 1,441; 95% CI 1,089–1,907 and IR 5,136; 95% CI 5,065–5,209, respectively) which following adjustment corresponded to a HR of 0.71 (95% CI 0.49–1.03). Tubal ligation was associated with lower risk of EC as well as mortality rates in women with EC. Elective tubal ligation may be adopted in future cancer preventive strategies but must be balanced against the irreversibility of the procedure, which preclude further unassisted reproduction.     

Prognosis of cancer in persons with infrequent consultations in general practice: A population‐based cohort study

Cancer survival rates are lower in Denmark than in comparable European countries. This may partly be attributable to subgroups of cancer patients who seek medical attention at late disease stages. It is unknown if differences in usual (i.e. customary) consultation frequency in general practice are associated with cancer prognosis. We aimed to estimate the cancer prognosis of cancer patients stratified by their usual consultation frequency in general practice. We performed a population‐based cohort study including 123,943 incident cancer patients aged 50 to 89 years diagnosed in Denmark in 2009 to 2013. We estimated associations between the patient's usual general practitioner (GP) consultation frequency 19 to 36 months before the cancer diagnosis and all‐cause mortality by using hazard ratios (HR), estimated by Cox proportional hazards regression. We also estimated the associations between the patient's usual GP consultation frequency and tumour stage, by using logistic regression estimates of odds ratios (ORs). Patients who usually did not see their GP (non‐consulters) had higher all‐cause mortality [HR = 1.39 (95% CI: 1.33–1.44)] compared to patients who usually saw their GP three to five times during an 18 months period (average consulters). Non‐consulters had higher odds of having distant tumour stage [OR = 1.46 (95% CI: 1.38–1.57)] than average consulters. Similar, yet less strong, patterns were seen among patients with low usual GP consultation frequency, yet not statistically significant for all cancer types. In conclusion, the association between usual GP non‐consultation and cancer prognosis is a combination of at least two things: a mechanism through more advanced tumour stage and other independent factors.     

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.     

Causes of death in patients diagnosed with gastric adenocarcinoma in Sweden, 1970‐2014: A population‐based study

The causes of death in patients with gastric adenocarcinoma have not been well characterized. This nationwide population‐based cohort study included 56 240 patients diagnosed with gastric adenocarcinoma in 1970‐2014 in Sweden. We used competing‐risks regression to compare cause‐specific risks of death in patients with different characteristics and a multiple‐cause approach to assess proportions of deaths attributable to each cause. Among 53 049 deaths, gastric cancer was the main (77.7% of all deaths) underlying cause. Other major underlying causes were nongastric malignancies (8.0%), ischemic heart disease or cerebrovascular disease (6.5%), and respiratory diseases (1.4%). Risk of death from gastric cancer steadily decreased in patients with cardia adenocarcinoma over the study period, but remained relatively stable in patients with noncardia adenocarcinoma since the 1980s. Risk of death from other malignancies increased during later calendar periods (subhazard ratio [SHR] = 2.16, 95% confidence interval [CI] 1.97‐2.38, comparing 2001‐2014 with 1970‐1980). Compared with men, the risk of death in women with cardia adenocarcinoma was higher from gastric cancer (SHR = 1.18, 95% CI 1.10‐1.27), but lower from other malignancies (SHR = 0.80, 95% CI 0.71‐0.91). In multiple‐cause models, 60.4%‐71.2% of all deaths were attributable to gastric cancer and 9.5%‐12.1% to other malignancies. The temporal trends of cause‐specific risks from multiple‐cause models were similar to those of underlying causes. Our findings suggest that although most deaths in patients with gastric adenocarcinoma are due to gastric cancer, other causes of death are common. Patients with cardia adenocarcinoma face considerable increasing risk of death from other causes over time, particularly from other malignancies.     

A population‐based prospective study of energy‐providing nutrients in relation to all‐cause cancer mortality and cancers of digestive organs mortality

The effect of dietary composition on mortality in low‐income countries is largely unknown. We evaluated whether percentages of dietary energy derived from protein, fat and carbohydrates were associated with all‐cause and cancer mortalities in a Bangladeshi population. Data from a prospective population‐based cohort study of 17,244 men and women were used. Percentages of dietary energy derived from protein, fat and carbohydrates, assessed using a validated food‐frequency questionnaire at baseline, were analyzed in relation to mortality over an average of 9 years (155,126 person‐years) of follow‐up. Cox proportional hazards regression models were used to estimate hazard ratios for all cause, all cancer and cancers of the digestive organs mortalities. Percentage of dietary energy from protein appeared to be significantly associated with cancer mortality. Fully adjusted hazard ratios for cancer mortality in increasing tertiles of percentage of dietary energy from protein were 1.0 (reference), 1.21 (0.73, 2.00) and 1.84 (1.08, 3.15) (p for trend = 0.023). These associations were much stronger for deaths from cancers of the digestive organs with fully adjusted hazard ratios in increasing tertiles of percentage of dietary energy from protein being 1.0 (reference), 2.25 (0.91, 5.59) and 4.85 (1.88, 12.51) (p for trend = 0.001). No significant associations in relation to cancer‐related mortality were observed for percentage of dietary energy from fat. Novel findings from this prospective study show protein is an important risk factor or proxy to an important risk factor for cancer mortality especially from digestive organ cancers in Bangladesh. © 2013 UICC     

Public health insurance and cancer‐specific mortality risk among patients with breast cancer: A prospective cohort study in China

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer‐specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer‐specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer‐specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow‐up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer‐specific mortality (95% CI 0%‐65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer‐specific mortality (95% CI 11%‐82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%‐12%) reduction in cancer‐specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%‐39%). Our findings suggest that underinsured patients face a higher risk of breast cancer‐specific mortality in developing countries.     

Dietary fiber intake and ovarian cancer risk: a prospective cohort study

There is some evidence from case–control studies that dietary fiber intake might be inversely associated with ovarian cancer risk, but there are limited prospective data. Therefore, we examined ovarian cancer risk in association with intake of dietary fiber in a prospective cohort of 49,613 Canadian women enrolled in the National Breast Screening Study (NBSS), who completed a self-administered food frequency questionnaire between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. Data from the food frequency questionnaire were used to estimate intake of total dietary fiber, of fiber fractions, and of fiber from various sources. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between energy-adjusted quartile levels of fiber intake and ovarian cancer risk. During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases. Total dietary fiber and fiber fractions were not associated with ovarian cancer risk in this study population.     

Cause‐specific long‐term mortality in survivors of childhood cancer in Switzerland: A population‐based study

Survivors of childhood cancer have a higher mortality than the general population. We describe cause‐specific long‐term mortality in a population‐based cohort of childhood cancer survivors. We included all children diagnosed with cancer in Switzerland (1976–2007) at age 0–14 years, who survived ≥5 years after diagnosis and followed survivors until December 31, 2012. We obtained causes of death (COD) from the Swiss mortality statistics and used data from the Swiss general population to calculate age‐, calendar year‐, and sex‐standardized mortality ratios (SMR), and absolute excess risks (AER) for different COD, by Poisson regression. We included 3,965 survivors and 49,704 person years at risk. Of these, 246 (6.2%) died, which was 11 times higher than expected (SMR 11.0). Mortality was particularly high for diseases of the respiratory (SMR 14.8) and circulatory system (SMR 12.7), and for second cancers (SMR 11.6). The pattern of cause‐specific mortality differed by primary cancer diagnosis, and changed with time since diagnosis. In the first 10 years after 5‐year survival, 78.9% of excess deaths were caused by recurrence of the original cancer (AER 46.1). Twenty‐five years after diagnosis, only 36.5% (AER 9.1) were caused by recurrence, 21.3% by second cancers (AER 5.3) and 33.3% by circulatory diseases (AER 8.3). Our study confirms an elevated mortality in survivors of childhood cancer for at least 30 years after diagnosis with an increased proportion of deaths caused by late toxicities of the treatment. The results underline the importance of clinical follow‐up continuing years after the end of treatment for childhood cancer.     

Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan

Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor‐tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population‐based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non‐statins and 41 statins users who had undergone EGFR‐TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan‐Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non‐statins group (4‐y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%‐81.4% vs. 85.5%; 95% CI, 78.5%‐98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29‐0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41‐0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR‐TKIs and played a synergistic anticancer role.