Lower Risk Of Cancer Mortality Research Articles

Cancer Specific Mortality in Insulin-Treated Type 2 Diabetes Patients

AimsTo test the hypothesis that cumulative exposure to insulin and long-acting insulin analogs might be associated with cancer mortality in diabetes patients.MethodsAll consecutive diabetes patients aged over 40 years, residing in a major urban area were screened at their first diabetes outpatient visit between 01/01/2001-12/31/2008 (n = 79869). Exclusion criteria were insulin treatment at screening, no insulin treatment until 12/31/2008, less than 6 months of glucose-lowering treatment alone before insulin initiation, insulin prescription before glargine became available, age <40/≥80 years at first insulin prescription, and <6 months of insulin exposure. A total 4990 subjects were followed-up for death based on death certificate, until 12/31/2011. Adjusted time-dependent competing risk regression analysis, with daily updates of treatment modalities was performed. Results are expressed for every 10,000 IU of cumulative dose or one year of cumulative time exposure to insulin.ResultsMean baseline age was 62±9 years, and follow-up 4.7±1.9 years. Glargine cumulative dose was associated with lower cancer mortality risk (subhazard ratio, SHR: 0.94 (95%CI 0.89–0.99, p = 0.033)). Cumulative exposure limited to that attained one year prior to death revealed lower SHRs for cumulative time (0.94 (95%CI 0.89–0.99, p = 0.018)) and cumulative dose of glargine (0.92 (95%CI 0.86–0.98, p = 0.014)). Glargine cumulative time and cumulative dose were significant predictors for lower pancreatic and breast cancer mortality, but not for deaths from lung, colorectal, female genital, liver, and urinary tract cancer. No increased hazards were found for any other subtypes of insulins.ConclusionsThe cumulative dose exposure to insulin glargine was associated with a lower risk of cancer mortality in general, and of breast and pancreatic cancer in particular. This effect remained even after additional “fixed” cohort or propensity score analyses.

Age-period-cohort analysis on the cancer mortality in rural China: 1990–2010

BackgroundCancer has become a global health problem. China still suffers continuous increasing cancer mortality. To study the trend of cancer mortality in rural China, this paper established an Age-Period-Cohort model to discuss the age effect, period effect and cohort effect on cancer mortality in rural China.MethodsThe data were collected from the “China Health Statistical Yearbook” from 1990 to 2010. Collected data were analyzed by Age-Period-Cohort model and Intrinsic Estimation method.ResultsThe age effect on the total cancer mortality represented a V trend. Compared with Group 0–4, Group 5–9 showed 71.87% lower cancer mortality risk. Compared with Group 5–9, Group 75–79 showed 38 times higher cancer mortality risk. The period effect on the total cancer mortality risk weakened firstly but then increased. It increased by 35.70% from 1990 to 2010, showing an annual average growth of 1.79%. The cohort effect on the total cancer mortality risk weakened by totally 84.94% from 1906–1910 to 2005–2010. Three “deterioration periods” and three “improvement periods” were witnessed during this period. The malignant cancer mortality varied similarly with the total cancer mortality, while benign cancer mortality and other cancer mortality represented different variation laws.ConclusionsAlthough the total cancer mortality risk is increasing at an accelerated rate, cancer mortality risk in recent born year is decreasing, indicating very important impact of social change on the cancer mortality in rural China.

Housework Reduces All-Cause and Cancer Mortality in Chinese Men

BackgroundLeisure time physical activity has been extensively studied. However, the health benefits of non-leisure time physical activity, particular those undertaken at home on all-cause and cancer mortality are limited, particularly among the elderly.MethodsWe studied physical activity in relation to all-cause and cancer mortality in a cohort of 4,000 community-dwelling elderly aged 65 and older. Leisure time physical activity (sport/recreational activity and lawn work/yard care/gardening) and non-leisure time physical activity (housework, home repairs and caring for another person) were self-reported on the Physical Activity Scale for the Elderly. Subjects with heart diseases, stroke, cancer or diabetes at baseline were excluded (n = 1,133).ResultsAmong the 2,867 subjects with a mean age of 72 years at baseline, 452 died from all-cause and 185 died from cancer during the follow-up period (2001–2012). With the adjustment for age, education level and lifestyle factors, we found an inverse association between risk of all-cause mortality and heavy housework among men, with the adjusted hazard ratio (HR) of 0.72 (95%CI = 0.57–0.92). Further adjustment for BMI, frailty index, living arrangement, and leisure time activity did not change the result (HR = 0.71, 95%CI = 0.56–0.91). Among women, however, heavy housework was not associated with all-cause mortality. The risk of cancer mortality was significantly lower among men who participated in heavy housework (HR = 0.52, 95%CI = 0.35–0.78), whereas among women the risk was not significant. Men participated in light housework also were at lower risk of cancer mortality than were their counterparts, however, the association was not significant. Leisure time physical activity was not related to all-cause or cancer mortality in either men or women.ConclusionHeavy housework is associated with reduced mortality and cancer deaths over a 9-year period. The underlying mechanism needs further study.

Cancer Risk in Diabetic Patients Treated with Metformin: A Systematic Review and Meta-analysis

BackgroundA growing body of evidence has suggested that metformin potentially reduces the risk of cancer. Our objective was to enhance the precision of estimates of the effect of metformin on the risk of any-site and site-specific cancers in patients with diabetes.Methods/Principal FindingsWe performed a search of MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for pertinent articles published as of October 12, 2011, and included them in a systematic review and meta-analysis. We calculated pooled risk ratios (RRs) for overall cancer mortality and cancer incidence. Of the 21,195 diabetic patients reported in 6 studies (4 cohort studies, 2 RCTs), 991 (4.5%) cases of death from cancer were reported. A total of 11,117 (5.3%) cases of incident cancer at any site were reported among 210,892 patients in 10 studies (2 RCTs, 6 cohort studies, 2 case-control studies). The risks of cancer among metformin users were significantly lower than those among non-metformin users: the pooled RRs (95% confidence interval) were 0.66 (0.49–0.88) for cancer mortality, 0.67 (0.53–0.85) for all-cancer incidence, 0.68 (0.53–0.88) for colorectal cancer (n = 6), 0.20 (0.07–0.59) for hepatocellular cancer (n = 4), 0.67 (0.45–0.99) for lung cancer (n = 3).Conclusion/SignificanceThe use of metformin in diabetic patients was associated with significantly lower risks of cancer mortality and incidence. However, this analysis is mainly based on observational studies and our findings underscore the more need for long-term RCTs to confirm this potential benefit for individuals with diabetes.

Cardiorespiratory Fitness, Different Measures of Adiposity, and Total Cancer Mortality in Women

The objective was to examine associations among cardiorespiratory fitness (CRF), adiposity, and cancer mortality in women. Healthy women (N = 14,256) without cancer history completed a baseline health examination 1970-2005. Measures included BMI, percent body fat (%Fat), and CRF quantified as duration of a maximal treadmill test. CRF was classified as low (quintile 1), moderate (Q2-3), and high fit (Q4-5) by age. Standard BMI cutpoints were used, while participants were classified by %Fat quintiles. Cancer mortality rates were calculated following age, exam year, and smoking adjustment. During a mean follow-up period of 15.2 ± 9.4 years, 250 cancer deaths occurred. Adjusted mortality rates across BMI groups were 4.6, 5.7, and 8.8 (P trend 0.08); %Fat 3.0, 4.9, 2.9, 3.8, and 6.9 (P trend 0.17); and CRF 7.9, 5.5, and 2.9 (P trend 0.003). When grouped into categories of fit and unfit (upper 80% and lower 20% of CRF distribution), and using BMI as the adiposity exposure, cancer mortality rates of unfit-obese women were significantly higher than fit-normal weight women (9.8 vs. 4.1 deaths/10,000 woman-years; P = 0.02), while fit-overweight and fit-obese women had no greater risk of mortality than fit-normal weight women. Using %Fat as the adiposity exposure, unfit-obese women tended to have higher cancer mortality than fit-normal weight women (7.0 vs. 3.3 deaths/10,000 woman-years, P = 0.10). Higher levels of CRF are associated with lower cancer mortality risk in women and attenuate the risk of cancer mortality in overweight women. Using adiposity measures to estimate cancer mortality risk in women can be potentially misleading unless CRF is considered.

Survival advantage associated with metformin usage in patients with colorectal cancer (CRC) and type II noninsulin-dependent diabetes (NIDDM).

3618 Background: Patients with NIDDM have an increased risk of colorectal adenomas and CRC possibly mediated through the insulin growth factor receptor pathway. Metformin is associated with anticancer efficacy in preclinical models and a lower risk of cancer mortality in patients with NIDDM. We undertook to evaluate the difference in outcome in NIDDM patients with CRC based upon their medications taken for glycemic control. Methods: We conducted an IRB-approved (DR09-0719) retrospective analysis of 4,758 patients seen at a single institution (MD Anderson) with CRC between the years of 2005-2008, to determine the prevalence of NIDDM in this patient population, in addition to determining whether patient survival differs based upon their diabetic therapy. Results: 424 out of 4,758 CRC patients (8.9%) identified as having NIDDM. Gender, male:female 282:142 (67%, 33%), age, mean 62 years (range 31-91), stage I/II/III/IV 37:55:175:158 (8.7%, 12.9%, 41.2%, 37.2%). Overall survival (OS) for the 397 patients with follow-up data available, by univariable Kaplan Meier analysis, was 63.7 months (95% CI, 52.3-75.5). Patients with NIDDM and CRC treated with metformin as one of their diabetic medications had a survival of 76.9 months (95% CI, 61.4-102.4) as compared to 56.9 months in those patients not treated with metformin (95% CI, 44.8-68.8), p = 0.048. By using a Cox regression model adjusted for age, sex, race, body mass index, and initial stage of disease we demonstrated that NIDDM patients treated with metformin had a 30% improvement in OS when compared to NIDDM patients treated with other diabetic agents. There was a non-statistically significant trend toward higher complete and minor pathologic response rate (≤ 10% residual tumor) in NIDDM patients with rectal cancer receiving chemoradiation who were treated with metformin when compared to those who were not (14/19, 74% vs. 9/19, 47%, p=0.09). Conclusions: In this analysis the use of metformin in NIDDM patients with CRC was associated with an improved overall survival. While these results are consistent with the findings in other solid tumors they will need to be validated in other colorectal cancer data sets.

Retrospective evaluation of patients with colorectal cancer (CRC) and type II non-insulin-dependent diabetes (NIDDM).

507 Background: Patients with NIDDM have an increased risk of colorectal adenomas and CRC possibly mediated through the insulin growth factor receptor pathway. Metformin is associated with anticancer efficacy in preclinical models and a lower risk of cancer mortality in patients with NIDDM. We undertook to evaluate the difference in outcome in NIDDM patients with CRC based upon their medications taken for glycemic control. Methods: We conducted an IRB-approved (DR09-0719) retrospective analysis of 4,758 patients seen at a single institution (University of Texas M. D. Anderson) with CRC between the years of 2005-2008, to determine the prevalence of NIDDM in this patient population, in addition to determining whether patient survival differs based upon their diabetic therapy. Results: 425 out of 4,758 CRC patients (8.9%) were identified as having NIDDM. Gender, male:female 283:142 (67%, 33%), age, mean 62 years (range 31-91), stage I/II/III/IV 37:55:175:158 (8.7%, 12.9%, 41.2%, 37.2%). Overall survival (OS) for the 397 patients with follow-up data available, by univariable Kaplan Meier analysis, was 63.7 months (95% confidence interval (CI), 52.3-75.5). Patients with NIDDM and CRC treated with metformin as one of their diabetic medications had a survival of 76.9 months (95% CI, 61.4-102.4) as compared to 56.9 months in those patients not treated with metformin (95% CI, 44.8- 68.8), p = 0.048. By using a Cox regression model adjusted for age, sex, race, body mass index, and initial stage of disease we demonstrated that NIDDM patients treated with metformin had a 30% improvement in OS when compared to NIDDM patients treated with other diabetic agents. There was a non-statistically significant trend toward higher complete and minor pathologic response rate (≤ 10% residual tumor) in NIDDM patients with rectal cancer receiving chemoradiation who were treated with metformin when compared to those who were not (14/19, 74% vs. 9/19, 47%, p = 0.09). Conclusions: In this analysis the use of metformin in NIDDM patients with CRC was associated with an improved overall survival. While these results are consistent with the findings in other solid tumors they will need to be validated in other colorectal cancer data sets. No significant financial relationships to disclose.

Combined Effects Of Cardiorespiratory Fitness, Not Smoking, And Normal Waist Girth On Morbidity And Mortality

Physical inactivity, cigarette smoking, and obesity are key modifiable risk factors for coronary heart disease (CHD). Little is known about the relations between these combined risk factors and incident CHD and mortality. PURPOSE: We investigated the combined effects of cardiorespiratory fitness, not smoking, and normal waist girth on incident CHD and mortalities from cardiovascular disease (CVD), cancer, and all causes in men. METHODS: We followed 40,397 men, ages 20-79 yr, who completed a medical evaluation including a maximal treadmill exercise test and self-reported health habits at baseline examination. We defined a low-risk profile as not smoking, moderate- or high-fitness, and normal waist girth (<94 cm), respectively. The combined low-risk group was defined as satisfying all three above factors. There were 1,147 incident CHD (fatal and nonfatal CHD events) and 2,682 deaths (862 CVD, 985 cancers, and 835 others) during an average of 17.8 yr of follow-up (717,404 man-yr). RESULTS: After adjustment for age, examination year, alcohol intake, and family history of CHD, men who were at low-risk for these 3 factors had 70% lower risk of incident CHD (95% CI: 57%, 79%), 84% lower risk of CVD mortality (95% CI: 77%, 89%), 72% lower risk of cancer mortality (95% CI: 58%, 81%), and 75% lower risk of all-cause mortality (95% CI: 69%, 80%), respectively, as compared with men who had none of these low-risk factors (all p for trend <0.001). Associations persisted after additional adjustment for hypertension, diabetes, and high cholesterol (all p for trend <0.001). The CHD events in this population might have been reduced by 20% (95% CI: 11%, 29%) if they had been physically fit, not smoking, and had normal waist girth. Men with all three exposures had 2.2 times the risk of CHD (95% CI: 1.52, 3.09 p<0.001) compared with men with none of theses risk factors. This was equivalent to being 10.4 years older in chronological age. CONCLUSIONS: Moderate and high levels of cardiorespiratory fitness, not smoking, and normal waist girth are associated with a reduced risk of incident CHD and much lower mortality from CVD, cancer, and all causes in men.

Muscular Strength and Adiposity as Predictors of Adulthood Cancer Mortality in Men

We examined the associations between muscular strength, markers of overall and central adiposity, and cancer mortality in men. A prospective cohort study including 8,677 men ages 20 to 82 years followed from 1980 to 2003. Participants were enrolled in The Aerobics Centre Longitudinal Study, the Cooper Institute in Dallas, Texas. Muscular strength was quantified by combining 1-repetition maximal measures for leg and bench presses. Adiposity was assessed by body mass index (BMI), percent body fat, and waist circumference. Cancer death rates per 10,000 person-years adjusted for age and examination year were 17.5, 11.0, and 10.3 across incremental thirds of muscular strength (P = 0.001); 10.9, 13.4, and 20.1 across BMI groups of 18.5-24.9, 25.0-29.9, and > or =30 kg/m(2), respectively (P = 0.008); 11.6 and 17.5 for normal (<25%) and high percent body fat (> or =25%), respectively (P = 0.006); and 12.2 and 16.7 for normal (< or =102 cm) and high waist circumference (>102 cm), respectively (P = 0.06). After adjusting for additional potential confounders, hazard ratios (95% confidence intervals) were 1.00 (reference), 0.65 (0.47-0.90), and 0.61 (0.44-0.85) across incremental thirds of muscular strength, respectively (P = 0.003 for linear trend). Further adjustment for BMI, percent body fat, waist circumference, or cardiorespiratory fitness had little effect on the association. The associations of BMI, percent body fat, or waist circumference with cancer mortality did not persist after further adjusting for muscular strength (all P > or = 0.1). Higher levels of muscular strength are associated with lower cancer mortality risk in men, independent of clinically established measures of overall and central adiposity, and other potential confounders.

Cardiorespiratory Fitness as a Predictor of Cancer Mortality Among Men With Pre-Diabetes and Diabetes

The purpose of this article was to examine the risk of cancer mortality across levels of fitness and to examine the fitness-mortality relation for site-specific cancers in men with pre-diabetes and diabetes. We examined the fitness-mortality relation for all-cause and site-specific cancer mortality among 18,858 men with pre-diabetes and 2,805 men with diabetes (aged 46.3 +/- 9.7 years [mean +/- SD]) from the Aerobics Center Longitudinal Study. We identified 719 cancer deaths during 354,558 person-years of risk. The duration of follow-up was 16.4 +/- 7.8 years (range <1-30.0 years). In men with pre-diabetes, moderate (hazard ratio 0.71 [95% CI 0.57-0.88]) and high fitness (0.76 [0.60-0.96]) were associated with lower risks of cancer mortality compared with the low-fit group in a model adjusted for age, examination year, smoking, alcohol use, fasting glucose concentration, previous cancer, and BMI. Similarly, for individuals with diabetes, moderate (0.53 [0.35-0.82]) and high fitness (0.44 [0.26-0.73]) were associated with lower risks of cancer mortality compared with the low-fit group. Among all men, being fit was associated with a lower risk of mortality from gastrointestinal (0.55 [0.39-0.77]), colorectal (0.53 [0.30-0.96]), liver (0.22 [0.07-0.71]), and lung cancer (0.43 [0.30-0.60]). In men with pre-diabetes and diabetes, higher levels of cardiorespiratory fitness were associated with lower risk of cancer mortality, particularly as a result of cancers of the gastrointestinal tract, compared with those who had low levels of fitness.

Cardiorespiratory Fitness, Different Measures of Adiposity, and Cancer Mortality in Men

The purpose was to examine the prospective relationship among cardiorespiratory fitness level (CRF), different measures of adiposity, and cancer mortality in men. Participants were 38,410 apparently healthy men who completed a comprehensive baseline health examination between 1970 and 2001. Clinical measures included BMI, waist circumference (WC), percent body fat, and CRF quantified as duration of a maximal treadmill exercise test. Participants were divided into fifths of CRF, BMI, WC, and percent body fat. Hazard ratios were computed with Cox regression analysis. During a mean follow-up period of 17.2 +/- 7.9 years, 1037 cancer deaths occurred. Adjusted hazard ratios across incremental BMI quintiles were 1.0, 1.23, 1.15, 1.39, and 1.72; those of WC were 1.0, 1.05, 1.03, 1.31, and 1.64; those of percent body fat were 1.0, 1.24, 1.17, 1.23, and 1.50; and those of CRF were 1.0, 0.70, 0.67, 0.70, and 0.49 (trend p < 0.01 for each). Further adjustment for CRF eliminated the significant trend in mortality risk across percent body fat groups and attenuated the trend in risk across BMI and WC groups. Adjustment of CRF for adiposity measures had little effect on mortality risk. When grouped into categories of fit and unfit (upper 80% and lower 20% of CRF distribution, respectively), mortality rates (per 10,000 man-years) were significantly lower in fit compared with unfit men within each stratum of BMI, WC, and percent body fat. Higher levels of CRF are associated with lower cancer mortality risk in men, independently of several adiposity measures.

The Relation of Cardiorespiratory Fitness and Adiposity With Cancer Mortality in Men

Low cardiorespiratory fitness (CRF) and overweight are associated with increased cancer mortality. PURPOSE: To explore the relation between baseline CRF, various measures of adiposity and cancer mortality in men. METHODS: 38,410 men (mean age 43.8 + 9.9 years) who were without known cancer, underwent a comprehensive preventive health examination at the Cooper Clinic between 1970–2001. Clinical measures included Body Mass Index (BMI), waist circumference (WC), percent body fat (%fat), and CRF from a maximal treadmill exercise test. Participants were divided into quartiles of CRF, BMI, WC, and % fat. Mortality surveillance was completed through December 31, 2003. Hazard ratios were computed with Cox regression analysis. RESULTS: During a mean follow-up period of 17.2 years, 1,037 cancer deaths occurred. Following adjustment for age, examination year, baseline health status and smoking status, hazard ratios across incremental BMI quartiles were 1.0, 1.07, 1.13, and 1.46; those of WC were 1.0, 0.98, 1.03, and 1.56; those of %fat were 1.0, 1.12, 1.09, and 1.31; and those of CRF were 1.0, 0.83,0.75, and 0.61 (trend p < 0.01 for each). Further adjustment for CRF eliminated the cancer mortality risk associated with %fat, and attenuated the risk associated with BMI and WC. Adjustment of CRF for adiposity measures had little effect on mortality risk. Restricting analyses to only men with greater than 3 years of follow-up did not materially change the results reported above. CONCLUSION: Higher levels of CRF are associated with lower cancer mortality risk in men, independent of several adiposity measures. These findings underscore the importance of CRF in addition to adiposity, as a determinant of cancer mortality in men. Supported by NIH grants AG06945 and HL 62508

CARDIORESPIRATORY FITNESS AND CANCER MORTALITY IN MEN WITH DIABETES

Diabetes has been associated with an increase in risk for many cancers, including pancreatic, biliary, and colorectal cancers. Moderate to high cardiorespiratory fitness (CRF) protects against cancer and overall mortalit y in healthy men. However, the effect of CRF on cancer mortality in men with diabetes is unknown. PURPOSE To determine the effect of CRF on cancer mortality in men with diabetes. METHODS Participants were 1992 men with diabetes mellitus, average age 48.7 years (SD 9.3 years), who received a medical examination and a maximal exercise test during 1970 to 1995, with mortality follow-up to December 31, 1996. Four fitness quartiles were created based on treadmill time. Relative risks of mortality were evaluated using proportional hazards models adjusted for age, exam year, history of cancer, and smoking. Linear trends between fitness and mortality were evaluated by including treadmill time as a continuous variable. RESULTS From this cohort, 71 cancer deaths were identified in 29,843 man-years of observation: 6 prostate, 13 respiratory tract, 24 gastrointestinal (6 colon, 9 pancreatic), 11 lymphomas, and 17 other cancers. Risk of cancer mortality was inversely associated with CRF (p for trend < 0.0001). The hazard ratios (HR) for mortality when compared with the highest fitness quartile were: Quartile 1 (HR 6.6; 95% CI 2.3–19.3), Quartile 2 (HR 4.1; 95% CI 1.4–12.0), Quartile 3 (HR 2.2; 95% CI 1.3–3.7). CONCLUSION High levels of CRF were associated with lower risk of cancer mortality in men with diabetes. Supported in part by NIH research grant AG06945.

Mortality in the era of deinstitutionalization.

The authors examined the 3 1/2-year mortality rate of 1,033 psychiatric patients who had received inpatient treatment during a 1-year period, using standardized mortality ratios to identify heightened risk. Deaths due to accidents or suicides and pneumonia occurred more frequently than expected. Deaths due to cancer occurred primarily among alcoholics; nonalcoholic patients had a significantly lower cancer mortality risk. The risk associated with age was greatest for young patients in general, but male schizophrenic patients and female alcoholics died at particularly young ages. The highest mortality risk associated with diagnosis was for male patients with affective disorders. The authors discuss the implications of these findings.