Peter T. Campbell

Leisure Time Spent Sitting in Relation to Total Mortality in a Prospective Cohort of US Adults

The obesity epidemic is attributed in part to reduced physical activity. Evidence supports that reducing time spent sitting, regardless of activity, may improve the metabolic consequences of obesity. Analyses were conducted in a large prospective study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality. Time spent sitting and physical activity were queried by questionnaire on 53,440 men and 69,776 women who were disease free at enrollment. The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up. After adjustment for smoking, body mass index, and other factors, time spent sitting (> or = 6 vs. <3 hours/day) was associated with mortality in both women (relative risk = 1.34, 95% confidence interval (CI): 1.25, 1.44) and men (relative risk = 1.17, 95% CI: 1.11, 1.24). Relative risks for sitting (> or = 6 hours/day) and physical activity (<24.5 metabolic equivalent (MET)-hours/week) combined were 1.94 (95% CI: 1.70, 2.20) for women and 1.48 (95% CI: 1.33, 1.65) for men, compared with those with the least time sitting and most activity. Associations were strongest for cardiovascular disease mortality. The time spent sitting was independently associated with total mortality, regardless of physical activity level. Public health messages should include both being physically active and reducing time spent sitting.

Leisure Time Physical Activity and Mortality: A Detailed Pooled Analysis of the Dose-Response Relationship

IMPORTANCE The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic-equivalent hours per week) of aerobic activity for substantial health benefit and suggested additional benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear. OBJECTIVE To quantify the dose-response association between leisure time physical activity and mortality and define the upper limit of benefit or harm associated with increased levels of physical activity. DESIGN, SETTING, AND PARTICIPANTS We pooled data from 6 studies in the National Cancer Institute Cohort Consortium (baseline 1992-2003). Population-based prospective cohorts in the United States and Europe with self-reported physical activity were analyzed in 2014. A total of 661,137 men and women (median age, 62 years; range, 21-98 years) and 116,686 deaths were included. We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. EXPOSURES Leisure time moderate- to vigorous-intensity physical activity. MAIN OUTCOMES AND MEASURES The upper limit of mortality benefit from high levels of leisure time physical activity. RESULTS Compared with individuals reporting no leisure time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR, 0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI, 0.59-0.62]); however, compared with the recommended minimum, the additional benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose-response relationship was observed for mortality due to cardiovascular disease and to cancer. CONCLUSIONS AND RELEVANCE Meeting the 2008 Physical Activity Guidelines for Americans minimum by either moderate- or vigorous-intensity activities was associated with nearly the maximum longevity benefit. We observed a benefit threshold at approximately 3 to 5 times the recommended leisure time physical activity minimum and no excess risk at 10 or more times the minimum. In regard to mortality, health care professionals should encourage inactive adults to perform leisure time physical activity and do not need to discourage adults who already participate in high-activity levels.

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.

Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults

IMPORTANCE Leisure-time physical activity has been associated with lower risk of heart-disease and all-cause mortality, but its association with risk of cancer is not well understood. OBJECTIVE To determine the association of leisure-time physical activity with incidence of common types of cancer and whether associations vary by body size and/or smoking. DESIGN, SETTING, AND PARTICIPANTS We pooled data from 12 prospective US and European cohorts with self-reported physical activity (baseline, 1987-2004). We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of leisure-time physical activity with incidence of 26 types of cancer. Leisure-time physical activity levels were modeled as cohort-specific percentiles on a continuous basis and cohort-specific results were synthesized by random-effects meta-analysis. Hazard ratios for high vs low levels of activity are based on a comparison of risk at the 90th vs 10th percentiles of activity. The data analysis was performed from January 1, 2014, to June 1, 2015. EXPOSURES Leisure-time physical activity of a moderate to vigorous intensity. MAIN OUTCOMES AND MEASURES Incident cancer during follow-up. RESULTS A total of 1.44 million participants (median [range] age, 59 [19-98] years; 57% female) and 186 932 cancers were included. High vs low levels of leisure-time physical activity were associated with lower risks of 13 cancers: esophageal adenocarcinoma (HR, 0.58; 95% CI, 0.37-0.89), liver (HR, 0.73; 95% CI, 0.55-0.98), lung (HR, 0.74; 95% CI, 0.71-0.77), kidney (HR, 0.77; 95% CI, 0.70-0.85), gastric cardia (HR, 0.78; 95% CI, 0.64-0.95), endometrial (HR, 0.79; 95% CI, 0.68-0.92), myeloid leukemia (HR, 0.80; 95% CI, 0.70-0.92), myeloma (HR, 0.83; 95% CI, 0.72-0.95), colon (HR, 0.84; 95% CI, 0.77-0.91), head and neck (HR, 0.85; 95% CI, 0.78-0.93), rectal (HR, 0.87; 95% CI, 0.80-0.95), bladder (HR, 0.87; 95% CI, 0.82-0.92), and breast (HR, 0.90; 95% CI, 0.87-0.93). Body mass index adjustment modestly attenuated associations for several cancers, but 10 of 13 inverse associations remained statistically significant after this adjustment. Leisure-time physical activity was associated with higher risks of malignant melanoma (HR, 1.27; 95% CI, 1.16-1.40) and prostate cancer (HR, 1.05; 95% CI, 1.03-1.08). Associations were generally similar between overweight/obese and normal-weight individuals. Smoking status modified the association for lung cancer but not other smoking-related cancers. CONCLUSIONS AND RELEVANCE Leisure-time physical activity was associated with lower risks of many cancer types. Health care professionals counseling inactive adults should emphasize that most of these associations were evident regardless of body size or smoking history, supporting broad generalizability of findings.

Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis

BACKGROUND & AIMS Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. METHODS We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. RESULTS Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 × 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10(-7)). CONCLUSIONS In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.

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.

Case–Control Study of Overweight, Obesity, and Colorectal Cancer Risk, Overall and by Tumor Microsatellite Instability Status

BACKGROUND Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status. METHODS The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (> or =30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. RESULTS Recent BMI, modeled in 5 kg/m(2) increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P = .22). Recent BMI, per 5 kg/m(2), was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31). CONCLUSION The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.

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.

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.

A yearlong exercise intervention decreases CRP among obese postmenopausal women.

PURPOSE To investigate the effect of a yearlong moderate-intensity aerobic exercise intervention on C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) among overweight or obese postmenopausal women. METHODS In a randomized controlled trial, 115 postmenopausal, overweight or obese, sedentary women, aged 50-75 yr were randomized to an aerobic exercise intervention of moderate-intensity (60%-75% observed maximal HR), for > or = 45 min x d(-1), 5 d x wk (n = 53), or to a 1-d x wk(-1) stretching control (n = 62), on an intent-to-treat basis. CRP, SAA, and IL-6 were measured at baseline, at 3 months, and at 12 months. RESULTS From baseline to 12 months, CRP decreased 10% in exercisers and increased 12% in controls (P = 0.01); no effects were observed for SAA and IL-6. Among participants at baseline who were obese (body mass index (BMI) > or = 30 kg x m(-2)) or had abdominal obesity (waist circumference (WC) > or = 88 cm), exercise resulted in a more pronounced reduction in CRP (BMI > or = 30 kg x m(-2), P = 0.002; WC > or = 88 cm, P < 0.0001), borderline for SAA (BMI > or = 30 kg x m(-2), P = 0.08; WC > or = 88 cm, P = 0.04); no intervention effects were observed among women who did not have these characteristics. Overall, weight loss was minimal in the exercise intervention ( approximately 1.8 kg). Linear trends were observed between CRP and 12-month changes in aerobic fitness (Ptrend = 0.006), exercise adherence (Ptrend = 0.004), percentage body fat (Ptrend = 0.002), body weight (Ptrend = 0.002), WC (Ptrend = 0.02), and intra-abdominal fat (Ptrend = 0.03). CONCLUSIONS A moderate-intensity exercise intervention reduced CRP for 12 months among women who were obese at baseline. These findings support the role of exercise in modulating inflammatory processes that are related to increased risk of chronic disease among obese women.