Christina C. Newton

Waist Circumference and All-Cause Mortality in a Large US Cohort

BACKGROUND Waist circumference (WC), a measure of abdominal obesity, is associated with higher mortality independent of body mass index (BMI). Less is known about the association between WC and mortality within categories of BMI or for the very high levels of WC that are now common. METHODS We examined the association between WC and mortality among 48,500 men and 56,343 women, 50 years or older, in the Cancer Prevention Study II Nutrition Cohort. A total of 9315 men and 5332 women died between 1997 and the end of follow-up in 2006. RESULTS After adjustment for BMI and other risk factors, very high levels of WC were associated with an approximately 2-fold higher risk of mortality in men and women (among men, relative risk [RR]=2.02; 95% confidence interval [CI], 1.71-2.39 for WC>or=120 cm compared with <90 cm; among women, RR=2.36; 95% CI, 1.98-2.82 for WC>or=110 cm compared with <75 cm). The WC was positively associated with mortality within all categories of BMI. In men, a 10-cm increase in WC was associated with RRs of 1.16 (95% CI, 1.09-1.23), 1.18 (95% CI, 1.12-1.24), and 1.21 (95% CI, 1.13-1.30) within normal (18.5 to <25), overweight (25 to <30), and obese (>or=30) BMI categories, respectively. In women, corresponding RRs were 1.25 (95% CI, 1.18-1.32), 1.15 (95% CI, 1.08-1.22), and 1.13 (95% CI, 1.06-1.20). CONCLUSION These results emphasize the importance of WC as a risk factor for mortality in older adults, regardless of BMI.

Diabetes and Cause-Specific Mortality in a Prospective Cohort of One Million U.S. Adults

OBJECTIVE Diabetes is a major predictor of death from heart disease and stroke; its impact on nonvascular mortality, including specific cancers, is less understood. We examined the association of diabetes with cause-specific mortality, including deaths from specific cancers. RESEARCH DESIGN AND METHODS A prospective cohort of 1,053,831 U.S. adults, without cancer at baseline, enrolled in the Cancer Prevention Study-II in 1982 and was followed for mortality until December 2008. At baseline, participants completed a self-administered questionnaire that included information on diabetes, smoking, physical activity, height, and weight. Multivariable-adjusted relative risks (RRs) (95% CI) were estimated using Cox proportional hazards regression. RESULTS During 26 years of follow-up, 243,051 men and 222,109 women died. In multivariable models that controlled for age, BMI, and other variables, diabetes was associated with higher risk of all-cause mortality (women RR 1.90 [95% CI 1.87–1.93]; men 1.73 [1.70–1.75]). Among women, diabetes was associated with higher risk of death from cancers of the liver (1.40 [1.05–1.86]), pancreas (1.31 [1.14–1.51]), endometrium (1.33 [1.08–1.65]), colon (1.18 [1.04–1.33]), and breast (1.16 [1.03–1.29]). Among men, diabetes was associated with risk of death from cancers of the breast (4.20 [2.20–8.04]), liver (2.26 [1.89–2.70]), oral cavity and pharynx (1.44 [1.07–1.94]), pancreas (1.40 [1.23–1.59]), bladder (1.22 [1.01–1.47]), colon (1.15 [1.03–1.29]), and (inversely) prostate (0.88 [0.79–0.97]). Diabetes was also associated with higher risks of death involving the circulatory system, respiratory system, digestive system, genitourinary system, and external causes/accidental deaths. CONCLUSIONS Diabetes is associated with higher risk of death for many diseases, including several specific forms of cancer.

Associations of Recreational Physical Activity and Leisure Time Spent Sitting With Colorectal Cancer Survival

PURPOSE Little is known about the association of recreational physical activity or leisure time spent sitting with survival after colorectal cancer diagnosis. This study examined the associations of prediagnosis and postdiagnosis recreational physical activity and leisure time spent sitting with mortality among patients with colorectal cancer. PATIENTS AND METHODS From a cohort of adults without colorectal cancer at baseline in 1992-1993, we identified 2,293 participants who were diagnosed with invasive, nonmetastatic colorectal cancer up to mid-2007. At baseline, before their cancer diagnosis, and again after their cancer diagnosis, participants completed detailed questionnaires that included information concerning recreational physical activity and leisure time spent sitting. RESULTS During a maximum follow-up of 16.1 years after colorectal cancer diagnosis, 846 patients with colorectal cancer died, 379 of them from colorectal cancer. Engaging in 8.75 or more metabolic equivalent (MET) hours per week of recreational physical activity (equivalent to approximately 150 minutes per week of walking) compared with fewer than 3.5 MET hours per week was associated with lower all-cause mortality (prediagnosis physical activity: relative risk [RR], 0.72; 95% CI, 0.58 to 0.89; postdiagnosis physical activity: RR, 0.58; 95% CI, 0.47 to 0.71). Spending 6 or more hours per day of leisure time sitting compared with fewer than 3 hours per day was associated with higher all-cause mortality (prediagnosis sitting time: RR, 1.36; 95% CI, 1.10 to 1.68; postdiagnosis sitting time: RR, 1.27; 95% CI, 0.99 to 1.64). CONCLUSION More recreational physical activity before and after colorectal cancer diagnosis was associated with lower mortality, whereas longer leisure time spent sitting was associated with higher risk of death.

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.

Impact of Body Mass Index on Survival After Colorectal Cancer Diagnosis: The Cancer Prevention Study-II Nutrition Cohort

PURPOSE The impact of body mass index (BMI) on survival after colorectal cancer diagnosis is poorly understood. This study assessed the association of pre- and postdiagnosis BMI with all-cause and cause-specific survival among men and women diagnosed with colorectal cancer in a prospective cohort. PATIENTS AND METHODS Participants in the Cancer Prevention Study-II Nutrition Cohort reported weight and other risk factor information via a self-administered questionnaire at baseline in 1992 to 1993. Updated information on current weight and incident cancer was reported via periodic follow-up questionnaires. This analysis includes 2,303 cohort participants who were diagnosed with nonmetastatic colorectal cancer between baseline and mid 2007 and were observed for mortality from diagnosis through December 2008. RESULTS A total of 851 participants with colorectal cancer died during the 16-year follow-up period, including 380 as a result of colorectal cancer and 153 as a result of cardiovascular disease (CVD). In analyses of prediagnosis BMI (weight reported at baseline in 1992 to 1993; mean, 7 years before colorectal cancer diagnosis), obese BMI (≥ 30 kg/m(2)) relative to normal BMI (18.5 to 24.9 kg/m(2)) was associated with higher risk of mortality resulting from all causes (relative risk [RR], 1.30; 95% CI, 1.06 to 1.58), colorectal cancer (RR, 1.35; 95% CI, 1.01 to 1.80), and CVD (RR, 1.68; 95% CI, 1.07 to 2.65). Postdiagnosis BMI (based on weight reported; mean, 1.5 years after diagnosis) was not associated with all-cause or cause-specific mortality. CONCLUSION This study suggests that prediagnosis BMI, but not postdiagnosis BMI, is an important predictor of survival among patients with nonmetastatic colorectal cancer.

Prospective Study Reveals Associations Between Colorectal Cancer and Type 2 Diabetes Mellitus or Insulin Use in Men

BACKGROUND & AIMS Type 2 diabetes mellitus (DM) is associated with an increased risk of colorectal cancer (CRC); it is not clear if this association varies by sex or other factors. Insulin use might also be associated with CRC risk. We investigated associations of type 2 DM and insulin use with CRC risk. METHODS The Cancer Prevention Study II Nutrition Cohort is a prospective study of cancer incidence. In 1992 or 1993, adult participants (n = 184,194) completed a detailed, self-administered questionnaire. Follow-up questionnaires were sent in 1997 and every 2 years thereafter. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for covariates. RESULTS After exclusions, 73,312 men and 81,663 women remained in the final analytic cohort; 1567 men (227 with type 2 DM) and 1242 women (108 with type 2 DM) were diagnosed with colon or rectal cancer by 2007. Among men, type 2 DM was associated with increased risk of incident CRC compared to not having type 2 DM (RR: 1.24; 95% CI: 1.08-1.44); risk was higher for participants with type 2 DM using insulin (RR: 1.36; 95% CI: 1.05-1.78), and participants with type 2 DM not using insulin (RR: 1.22, 95% CI: 1.04-1.45). Among women, type 2 DM and insulin use were not associated with risk of incident CRC (RR: 1.01; 95% CI: 0.82-1.23 and RR: 0.95; 95% CI: 0.64-1.41, respectively). CONCLUSIONS There is a modest association between type 2 DM and CRC among men, but not women. Insulin use is not associated with a substantially increased risk of CRC.

Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).

A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case‐control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case‐control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate‐adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19–2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52–1.31), breast cancer (OR = 1.21, 95% CI = 0.97–1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.

Impact of Diabetes Mellitus and Insulin Use on Survival After Colorectal Cancer Diagnosis: The Cancer Prevention Study-II Nutrition Cohort

PURPOSE To examine the association between type 2 diabetes mellitus (T2DM) and survival among patients with colorectal cancer (CRC) and to evaluate whether this association varies by sex, insulin treatment, and durations of T2DM and insulin use. PATIENTS AND METHODS This study was conducted among 2,278 men and women diagnosed with nonmetastatic colon or rectal cancer between 1992 and 2007 in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of cancer incidence. In 1992 to 1993, participants completed a detailed, self-administrated questionnaire. Vital status and cause of death were ascertained through the end of 2008. Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression. RESULTS Among the 2,278 men and women with nonmetastatic CRC, there were 842 deaths by the end of follow-up (including 377 deaths from CRC and 152 deaths from cardiovascular disease [CVD]). Among men and women combined, compared with patients without T2DM, patients with CRC and T2DM were at higher risk of all-cause mortality (RR, 1.53; 95% CI, 1.28 to 1.83), CRC-specific mortality (RR, 1.29; 95% CI, 0.98 to 1.70), and CVD-specific mortality (RR, 2.16; 95% CI, 1.44 to 3.24), with no apparent differences by sex or durations of T2DM or insulin use. Insulin use, compared with no T2DM, was associated with increased risk of death from all causes (RR, 1.68; 95% CI, 1.22 to 2.31) and CVD (RR, 3.87; 95% CI, 2.12 to 7.08) but not from CRC (RR, 0.58; 95% CI, 0.28 to 1.19). CONCLUSION Patients with CRC and T2DM have a higher risk of mortality than patients with CRC who do not have T2DM, especially a higher risk of death from CVD.

Daily Aspirin Use and Cancer Mortality in a Large US Cohort

BACKGROUND A recent pooled analysis of randomized trials of daily aspirin for prevention of vascular events found a substantial reduction (relative risk [RR] = 0.63, 95% confidence interval [CI] = 0.49 to 0.82) in overall cancer mortality during follow-up occurring after 5 years on aspirin. However, the magnitude of the effect of daily aspirin use, particularly long-term use, on cancer mortality is uncertain. METHODS We examined the association between daily aspirin use and overall cancer mortality among 100 139 men and women with no history of cancer in the Cancer Prevention Study II Nutrition Cohort. Cox proportional hazards regression models were used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS Between 1997 and 2008, 5138 participants died from cancer. Compared with no use, daily aspirin use at baseline was associated with slightly lower cancer mortality, regardless of duration of daily use (for <5 years of use, RR = 0.92, 95% CI = 0.85 to 1.01; for ≥5 years of use, RR = 0.92, 95% CI = 0.83 to 1.02). Associations were slightly stronger in analyses that used updated aspirin information from periodic follow-up questionnaires and included 3373 cancer deaths (for <5 years of use, RR = 0.84, 95% CI = 0.76 to 0.94; for ≥5 years of use, RR = 0.84, 95% CI = 0.75 to 0.95). CONCLUSION These results are consistent with an association between recent daily aspirin use and modestly lower cancer mortality but suggest that any reduction in cancer mortality may be smaller than that observed with long-term aspirin use in the pooled trial analysis.

Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case‐control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case‐control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate‐adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19–2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52–1.31), breast cancer (OR = 1.21, 95% CI = 0.97–1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.