Abstract
Purpose
Accumulating evidence suggests an etiologic role in renal cell carcinoma (RCC) for physical activity. However, it is unknown if prolonged sitting, which is thought to be distinct from too little moderate-vigorous physical activity, is an independent risk factor for RCC. The authors prospectively examined the relationship of prolonged sitting and risk of RCC among 289,512 women and men in the National Institutes of Health—AARP Diet and Health Study.
Methods
From 1996 through 2006, 1206 invasive RCC cancer cases were identified. Cox proportional hazards regression was used to estimate multivariate hazard ratios (HR) and 95% confidence intervals (CI).
Results
After controlling for known risk factors for RCC, we did not find evidence of associations between RCC risk and time spent per day sitting while watching television or videos (HR7+hrs:<1 hr: 0.96 (0.66, 1.38), ptrend=0.707) or total sitting time (HR9+hrs: <3hrs: 1.11 (0.87, 1.41), ptrend=0.765).
Conclusion
Prolonged sitting time was not associated with RCC risk among men and women in this large cohort.
MESH keywords: sedentary lifestyle, kidney neoplasms, cohort studies
Introduction
Kidney and renal pelvis cancers together rank 8th in cancer incidence in the US, with over 58,000 new cases estimated for 2010 (1). Over 90% of cancers originating in the kidney are adenocarcinomas, or renal cell carcinomas (RCC), for which incidence has continued to rise (2). Accumulating evidence has suggested a role for physical activity in RCC etiology (2), as well as a relationship between sedentary behavior (e.g., prolonged sitting)—thought to be distinct from physical activity—and RCC risk factors such as obesity and cardio-metabolic health biomarkers (2). Yet no published studies have examined whether prolonged sitting is itself an RCC risk factor. Prolonged sitting may affect cancer risk by displacing light-intensity activities of daily living, which can lower physical activity energy expenditure and increase risk for weight gain and poor metabolic health (3-4). We hypothesized that time spent sitting while watching television or videos and total time spent sitting are positively associated with RCC risk, independent of physical activity and other relevant confounding factors.
Methods
Study population
The NIH-AARP Diet and Health Study has been described in detail elsewhere (5). In 1995-1996, participants completed a self-administered baseline questionnaire on demographic and anthropometric characteristics, dietary intake, and health-related behaviors. In 1996-1997, a second questionnaire was sent to collect more detailed information about cancer risk factors, including sedentary behavior (time spent watching television or videos and total time spent sitting in a typical 24 hour period), recreational moderate-vigorous physical activity (MVPA), and weight history (6-7). We did not have direct evidence of validity or reliability of the sedentary behavior or physical activity questions we asked; however, our questions were similar to questions from measures with reasonable validity and reliability that included assessment on television watching (8), sitting (9-10), and recreational moderate/vigorous activity (11-14).
334,889 respondents completed both questionnaires and prospective follow-up data. We excluded those who were proxies for the intended respondents (n=10,383), had prevalent cancer (n=18,862) or a cancer cause of death record only (n=983), had missing data on sedentary behavior (n=2,496) or MVPA (n=12,601), or had extreme or missing values for energy intake (n=2,349) or body mass index (BMI) (n=6375). After exclusions, our analytic cohort consisted of 119,237 women and 170,275 men, who were on average 63 years of age.
Cancer ascertainment
First primary invasive RCC cases through December 31, 2006 were identified through linkage with eleven state cancer registry databases. RCC was defined using the International Classification for Oncology code C649 and histology codes 8140-8570, 8940, and 8959.
Statistical analysis
Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated with Cox proportional hazards models (SAS Institute, v. 9.1.3). Person-years were calculated from the date the second questionnaire was received until cancer diagnosis, death, move-out of the registry areas, or the end of follow-up (December 31, 2006), whichever occurred first. The test for linear trend across categories of sedentary behavior was performed by assigning participants the median value of their categories and entering it as a continuous term in a regression model.
We adjusted for previously established RCC risk factors (see Table 1), except for education, family history of cancer, red meat intake, and menopausal hormone therapy use, which did not remain statistically significant (p<0.05) in our final multivariate model. We chose not to adjust for BMI and hypertension, because of their likelihood in the exposure-disease pathway; however, we report in the text on the further influence on risk estimates that adding these variables would make. We also explored whether associations differed by race, obesity, hypertension, or MVPA.
Table 1. Risk of RCC according to levels of sedentary behavior among 289,512 men and women in the NIH-AARP Diet and Health Study.
| Among Men and Women | |||||
|---|---|---|---|---|---|
| Hazard ratios (95% confidence intervals) | |||||
| Sitting while watching television/videos (hrs/d) | Cases | Person-years | Multivariate model without MVPA1 | Full model2 | |
| < 1 | 64 | 175,165 | 1.00 | 1.00 | |
| 1 to 2 | 322 | 732,110 | 1.06 (0.81, 1.39) | 1.06 (0.81, 1.39) | |
| 3 to 4 | 564 | 1,101,007 | 1.15 (0.88, 1.49) | 1.15 (0.88, 1.49) | |
| 5 to 6 | 203 | 376,608 | 1.15 (0.86, 1.53) | 1.15 (0.86, 1.53) | |
| 7+ | 53 | 120,262 | 0.96 (0.66, 1.39) | 0.96 (0.66, 1.38) | |
| ptrend | 0.692 | 0.707 | |||
| Total sitting (hrs/d) | |||||
| < 3 | 220 | 501,433 | 1.00 | 1.00 | |
| 3 to 4 | 402 | 731,624 | 1.20 (1.02, 1.42) | 1.20 (1.02, 1.42) | |
| 5 to 6 | 320 | 695,341 | 1.02 (0.86, 1.21) | 1.02 (0.86, 1.21) | |
| 7 to 8 | 166 | 367,315 | 1.05 (0.85, 1.28) | 1.04 (0.85, 1.27) | |
| 9+ | 98 | 209,439 | 1.12 (0.88, 1.42) | 1.11 (0.87, 1.41) | |
| ptrend | 0.832 | 0.765 | |||
| Among Men | |||||
| Hazard ratios (95% confidence intervals) | |||||
| Sitting while watching television/videos (hrs/d) | Cases | Person-years | Multivariate model without MVPA3 | Full model4 | |
| < 1 | 43 | 94,065 | 1.00 | 1.00 | |
| 1 to 2 | 251 | 437,352 | 1.16 (0.84, 1.60) | 1.16 (0.84, 1.60) | |
| 3 to 4 | 430 | 648,062 | 1.23 (0.90, 1.69) | 1.23 (0.90, 1.69) | |
| 5 to 6 | 151 | 206,100 | 1.26 (0.89, 1.77) | 1.25 (0.89, 1.77) | |
| 7+ | 34 | 58,193 | 0.98 (0.62, 1.54) | 0.97 (0.61, 1.53) | |
| ptrend | 0.702 | 0.743 | |||
| Total sitting (hrs/d) | |||||
| < 3 | 163 | 267,720 | 1.00 | 1.00 | |
| 3 to 4 | 302 | 422,922 | 1.17 (0.96, 1.41) | 1.16 (0.96, 1.41) | |
| 5 to 6 | 247 | 410,106 | 1.01 (0.83, 1.23) | 1.00 (0.82, 1.22) | |
| 7 to 8 | 121 | 216,994 | 0.97 (0.77, 1.23) | 0.96 (0.76, 1.22) | |
| 9+ | 76 | 126,030 | 1.10 (0.83, 1.44) | 1.08 (0.82, 1.42) | |
| ptrend | 0.602 | 0.524 | |||
| Among Women | |||||
| Hazard ratios (95% confidence intervals) | |||||
| Sitting while watching television/videos (hrs/d) | Cases | Person-years | Multivariate model without MVPA3 | Full model4 | |
| < 1 | 21 | 81,100 | 1.00 | 1.00 | |
| 1 to 2 | 71 | 294,758 | 0.87 (0.53, 1.42) | 0.87 (0.53, 1.42) | |
| 3 to 4 | 134 | 452,945 | 1.00 (0.63, 1.59) | 1.00 (0.63, 1.59) | |
| 5 to 6 | 52 | 170,508 | 0.96 (0.57, 1.61) | 0.96 (0.57, 1.62) | |
| 7+ | 19 | 62,069 | 0.95 (0.50, 1.79) | 0.96 (0.51, 1.82) | |
| ptrend | 0.758 | 0.700 | |||
| Total sitting (hrs/d) | |||||
| < 3 | 57 | 233,713 | 1.00 | 1.00 | |
| 3 to 4 | 100 | 308,702 | 1.32 (0.96, 1.84) | 1.32 (0.95, 1.84) | |
| 5 to 6 | 73 | 285,235 | 1.06 (0.75, 1.51) | 1.06 (0.75, 1.51) | |
| 7 to 8 | 45 | 150,321 | 1.30 (0.87, 1.93) | 1.31 (0.88, 1.95) | |
| 9+ | 22 | 83,409 | 1.17 (0.71, 1.93) | 1.20 (0.72, 1.99) | |
| ptrend | 0.631 | 0.572 | |||
Adjusted for age, sex, race, history of diabetes, smoking, alcohol intake, diet quality and energy intake
Adjusted for age, sex, race, history of diabetes, smoking, alcohol intake, diet quality, energy intake, and recreational moderate-vigorous physical activity
Adjusted for age, race, history of diabetes, smoking, alcohol intake, diet quality, energy intake, age at first live birth/parity (women only)
Adjusted for age, race, history of diabetes, smoking, alcohol intake, diet quality, energy intake, age at first live birth/parity (women only) , and recreational moderate-vigorous physical activity
Results
The HR of RCC for those who reported watching television or videos for 7 or more hours versus less than 1 hour per day was 0.96 (95% CI: 0.66, 1.38, ptrend=0.707) (Table 1). The HR for those whose total sitting time was 9 or more hours versus less than 3 hours per day was 1.11 (95% CI: 0.87, 1.41, ptrend=0.765). The associations were comparable for men and women separately. Additional adjustment for BMI and hypertension yielded parallel conclusions, and results were similar when we limited the analysis to clear cell tumors, the largest subtype (data not shown). We did not find evidence of effect modification by any of the investigated factors.
Discussion
In this study of nearly 300,000 men and women, we did not observe an association between prolonged sitting time and RCC. Our study is the first to examine this etiologic relationship and featured refined definitions of RCC using histology codes, measurement of important RCC risk factors, long-term follow-up, and a large sample size, affording us ample statistical power to detect an association.
We previously noted an inverse association between physical activity and RCC (15). While our data suggest that reducing sedentary time may not independently protect against RCC, we cannot rule out a weak association between sedentary behavior and RCC, which may have been masked by measurement error. However, sedentary behavior has been positively related to other obesity-related cancers (endometrial, colon) in our cohort (16-18).
Among older adults, “too much sitting” is prevalent health behavior and is thought to be distinct from “too little MVPA” given its own contextual determinants and possibly health effects (3). Additional research and improvements in sedentary behavior assessment may help improve our understanding of the health benefits associated with not only reducing but also breaking up prolonged sitting.
Acknowledgments
This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDC) under contract with the Florida Department of Health (FDOH). The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services.
We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation.
List of Abbreviations and Acronyms
- RCC
renal cell carcinoma
- MVPA
moderate-vigorous physical activity
- BMI
body mass index
- HR
hazard ratio
- CI
confidence interval
Footnotes
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Contributor Information
Stephanie M. George, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
Steven C. Moore, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
Wong-Ho Chow, Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
Arthur Schatzkin, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
Albert R. Hollenbeck, AARP.
Charles E. Matthews, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
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