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Higher physical activity levels have been associated with a lower risk of developing various cancers and all-cancer mortality, but the impact of pre-diagnosis physical activity on cancer-specific death has not been fully characterized. In the prospective National Institutes of Health-AARP Diet and Health Study with 293,511 men and women, we studied prediagnosis moderate to vigorous intensity leisure time physical activity (MVPA) in the past 10 years and cancer-specific mortality. Over a median 12.1 years, we observed 15,001 cancer deaths. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for MVPA with cancer mortality overall and by 20 specific cancer sites, adjusting for relevant risk factors. Compared to participants reporting never/rare MVPA, those reporting >7 hr/week MVPA had a lower risk of total cancer mortality (HR = 0.89, 95% CI 0.84–0.94; p-trend <0.001). When analyzed by cancer site-specific deaths, comparing those reporting >7 hr/week of MVPA to those reporting never/rare MVPA, we observed a lower risk of death from colon (HR = 0.70; 95% CI 0.57–0.85; p-trend <0.001), liver (0.71; 0.52–0.98; p-trend = 0.012) and lung cancer (0.84; 0.77–0.92; p-trend <0.001) and a significant p-trend for non-Hodgkins lymphoma (0.80; 0.62–1.04; p-trend = 0.017). An unexpected increased mortality p-trend with increasing MVPA was observed for death from kidney cancer (1.42; 0.98–2.03; p-trend = 0.016). Our findings suggest that higher prediagnosis leisure time physical activity is associated with lower risk of overall cancer mortality and mortality from multiple cancer sites. Future studies should confirm observed associations and further explore timing of physical activity and underlying biological mechanisms.
A recent annual report to the nation reported that more than one-third of U.S. men and women were considered to be physically inactive and that over half did not meet physical activity recommendations of 150 minutes of moderate to vigorous intensity activity each week. Physical activity has been related to lower cancer incidence for the breast, colon and endometrium and has also been associated with disease severity, recurrence and survival, particularly for breast and colorectal cancer.[3, 4] Existing studies on physical activity and mortality have shown an association between physical activity and lower risk of all cause[5, 6] and overall cancer mortality,[7-9] but the effect of leisure time physical activity on mortality from individual cancer sites has not been fully characterized.
We hypothesized that moderate to vigorous intensity leisure time physical activity (MVPA) would be inversely related to overall cancer death and that examination of physical activity in relation to specific cancer sites would generate hypotheses for future research. While physical activity and overall mortality have previously been examined in the National Institutes of Health (NIH)-AARP Diet and Health Study,[10, 11] the large, prospective nature and extended follow-up time in this cohort of men and women allowed for additional exploration of individual cancer sites. We thus analyzed pre-diagnosis physical activity and cancer-specific deaths in the NIH-AARP cohort to augment the paucity of evidence on physical activity and cancer mortality.
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Our analytic cohort included 293,511 participants (171,666 men and 121,845 women). The median time from MVPA assessment to cancer diagnosis was 5.2 years (range 0–13.2). Over a median 12.1 years, we observed 15,001 cancer deaths. Population characteristics are presented in Table 1. Compared to those reporting never/rare physical activity, those who reported higher levels of physical activity had a lower BMI and a healthier diet as scored by the HEI-2010. Active individuals were also more likely to be married or living as married, report regular multivitamin use and were less likely to report diabetes and smoking at baseline. Active women were less likely to report menarche at age <12 years.
We found a reduction in risk for overall cancer mortality with increasing MVPA (p-trend = <0.001), which reached statistical significance for those reporting greater than 1 hr per week of MVPA. Compared to those reporting never/rare MVPA, we observed a 7% lower risk for those reporting 1–3 MVPA hr/wk (HR = 0.93; 95% CI 0.88–0.98), a 10% lower risk for those reporting 4–7 hr/wk (0.90; 0.85–0.95) and a 11% lower risk for those reporting >7 hr/wk of MVPA (0.89; 0.84–0.94) (Table 2). Estimates for MVPA and cancer-specific mortality are presented in Table 2 by strongest inverse to strongest positive point estimates in the highest category of MVPA. We observed statistically significant inverse trends with higher MVPA for deaths due to cancers of the colon (HR = 0.70; 95% CI 0.57–0.85, p-trend = <0.001), liver (0.71; 0.52–0.98, p-trend = 0.012), lung (0.84; 0.77–0.92, p-trend = <0.001) and non-Hodgkins lymphoma (0.80; 0.62–1.04, p-trend = 0.017). In sensitivity analysis, excluding those diagnosed within two years of the MVPA questionnaire, the trend became nonsignificant for non-Hodgkins lymphoma (0.86; 0.62–1.19, p-trend = 0.176) (Supporting Information Table 1). No statistically significant trends were observed for lymphocytic leukemia, oral cavity and pharynx, esophagus, myeloma, myeloid/monocytic leukemia, stomach, ovarian, prostate, bladder, breast, brain, pancreas or rectum cancer deaths. We observed an unexpected statistically significant positive trend between MVPA and mortality from kidney cancer (1.42; 0.98–2.03, p-trend = 0.016), which remained significant in the analyses excluding individuals diagnosed within two years of MVPA assessment (1.67; 1.04–2.70, p-trend = 0.013) (Supporting Information Table 1).
Table 2. Associations between moderate to vigorous intensity physical activity (MVPA) and cancer mortality in the NIH-AARP study population (N = 293,511)a
| ||Never/rare|| ||<1|| ||1–3|| ||4–7|| ||>7|| |
|MVPA (hr/wk) Cancer death||No. of deaths||HR (ref.)||No. of deaths||HR (95% CI)||No. of deaths||HR (95% CI)||No. of deaths||HR (95% CI)||No. of deaths||HR (95% CI)||P trend|
|All cancers||2524||1.00||1659||0.95 (0.89–1.01)||3756||0.93 (0.88–0.98)||3636||0.90 (0.85–0.95)||3426||0.89 (0.84–0.94)||<0.001|
|Individual cancer sites by inverse magnitude of point estimate comparing MVPA >7 hr/wk to never/rare MVPA|
|Lymphocytic leukemia||20||1.00||14||0.96 (0.48–1.89)||46||1.30 (0.76–2.21)||24||0.65 (0.35–1.19)||24||0.68 (0.37–1.25)||0.058|
|Colonb||198||1.00||109||0.80 (0.63–1.01)||268||0.85 (0.70–1.02)||250||0.79 (0.65–0.96)||211||0.70 (0.57–0.85)||<0.001|
|Liver||82||1.00||43||0.79 (0.54–1.14)||112||0.90 (0.68–1.21)||78||0.64 (0.47–0.88)||82||0.71 (0.52–0.98)||0.012|
|Oral cavity and pharynx||38||1.00||20||0.83 (0.48–1.44)||41||0.79 (0.51–1.24)||38||0.76 (0.48–1.21)||36||0.75 (0.47–1.20)||0.217|
|Non-Hodgkins lymphoma||104||1.00||90||1.19 (0.90–1.58)||137||0.76 (0.58–0.98)||154||0.83 (0.64–1.06)||143||0.80 (0.62–1.04)||0.017|
|Esophagus||88||1.00||55||0.92 (0.65–1.29)||123||0. 91 (0.69–1.20)||127||0.96 (0.73–1.27)||98||0.80 (0.60–1.08)||0.251|
|Myeloma||61||1.00||34||0.75 (0.49–1.14)||63||0.56 (0.40–0.81)||90||0.77 (0.55–1.07)||93||0.82 (0.59–1.15)||0.579|
|Lung||923||1.00||522||0.85 (0.76–0.95)||1258||0.92 (0.84–1.00)||1095||0.82 (0.75–0.90)||1073||0.84 (0.77–0.92)||<0.001|
|Myeloid/monocytic leukemia||54||1.00||50||1.27 (0.86–1.86)||81||0.85 (0.60–1.21)||109||1.10 (0.79–1.54)||82||0.86 (0.60–1.22)||0.346|
|Stomach||49||1.00||34||1.00 (0.65–1.56)||77||0.99 (0.69–1.42)||76||0.97 (0.67–1.40)||68||0.90 (0.61–1.31)||0.541|
|Ovarianc||61||1.00||41||0.92 (0.62–1.36)||90||0.83 (0.59–1.15)||98||0.87 (0.63–1.21)||97||0.91 (0.65–1.26)||0.623|
|Prostate||80||1.00||55||0.97 (0.69–1.37)||107||0.79 (0.59–1.06)||145||1.03 (0.78–1.37)||126||0.93 (0.69–1.24)||0.968|
|Bladder||52||1.00||45||1.25 (0.84–1.86)||82||0.97 (0.68–1.38)||82||0.95 (0.67–1.36)||85||1.03 (0.72–1.46)||0.698|
|Breastb, c||70||1.00||55||1.21 (0.82–1.80)||103||0.92 (0.65–1.29)||99||0.97 (0.68–1.37)||109||1.08 (0.76–1.53)||0.973|
|Brain||57||1.00||51||1.14 (0.78–1.66)||115||1.03 (0.75–1.42)||107||0.91 (0.65–1.26)||128||1.14 (0.82–1.56)||0.791|
|Endometrialc, d||23||1.00||24||1.52 (0.85–2.69)||27||0.79 (0.45–1.38)||35||1.13 (0.66–1.93)||34||1.21 (0.70–2.08)||0.745|
|Pancreas||149||1.00||145||1.35 (1.07–1.70)||292||1.14 (0.93–1.39)||338||1.28 (1.05–1.56)||315||1.25 (1.03–1.53)||0.065|
|Kidney||47||1.00||36||1.10 (0.71–1.70)||85||1.14 (0.80–1.64)||106||1.47 (1.03–2.09)||93||1.42 (0.98–2.03)||0.016|
|Rectum||18||1.00||16||1.26 (0.64–2.48)||47||1.57 (0.90–2.71)||39||1.27 (0.72–2.25)||48||1.63 (0.93–2.84)||0.150|
To explore the possibility of effect modification by smoking, in Table 3 we present analyses stratified by smoking status for MVPA and cancer death overall and by cancer site. Multiplicative interaction was not observed for any of the cancer sites (all p-interactions <0.05) except for ovarian cancer death (p = 0.022). Still, stratified ovarian cancer death hazard ratios were not statistically significant for never (1.04; 0.99–1.09) or ever (0.96; 0.92–1.01) smokers.
Table 3. Associations for a 1 hr increase in moderate to vigorous intensity physical activity (MVPA) per week and cancer mortality in the NIH-AARP study population, stratified by smoking status (N = 293,511)a
| ||Total population||Never smokers||Ever Smokers|| |
|Type of cancer death||No. of events||HR (95% CI)||No. of events||HR (95% CI)||No. of events||HR (95% CI)||p-interaction|
|All cancers||15001||0.99 (0.98–0.99)b||3200||0.99 (0.98–1.00)||11,801||0.99 (0.98–0.99)b||0.782|
|Lymphocytic leukemia||128||0.93 (0.88–0.99)b||39||0.90 (0.81–1.00)b||89||0.95 (0.88–1.02)||0.744|
|Colon||1036||0.97 (0.95–0.99)b||309||0.98 (0.94–1.01)||727||0.96 (0.94–0.98)b||0.507|
|Liver||397||0.96 (0.93–0.99)b||118||0.92 (0.87–0.98)b||279||0.98 (0.94–1.02)||0.112|
|Oral cavity and pharynx||173||0.98 (0.93–1.02)||25||0.93 (0.81–1.06)||148||0.98 (0.93–1.04)||0.597|
|Non-Hodgkins lymphoma||628||0.97 (0.95–1.00)b||218||0.96 (0.92–1.01)||410||0.98 (0.95–1.01)||0.606|
|Esophagus||491||0.98 (0.96–1.01)||62||0.96 (0.89–1.05)||429||0.99 (0.96–1.02)||0.635|
|Myeloma||341||1.01 (0.97–1.04)||121||1.02 (0.96–1.08)||220||1.00 (0.96–1.05)||0.840|
|Lung||4871||0.98 (0.98–0.99)b||252||1.00 (0.96–1.04)||4619||0.98 (0.97–0.99)b||0.454|
|Myeloid/monocytic leukemia||376||0.99 (0.95–1.02)||100||0.99 (0.93–1.06)||276||0.98 (0.95–1.02)||0.884|
|Stomach||304||0.99 (0.95–1.02)||74||0.98 (0.91–1.05)||230||0.99 (0.95–1.04)||0.745|
|Ovarianc||387||1.00 (0.97–1.03)||184||1.04 (0.99–1.09)||203||0.96 (0.92–1.01)||0.022|
|Prostate||513||1.01 (0.98–1.03)||132||0.98 (0.93–1.04)||381||1.01 (0.98–1.05)||0.258|
|Bladder||346||0.99 (0.96–1.03)||60||0.94 (0.87–1.03)||286||1.00 (0.97–1.04)||0.433|
|Breastc||436||1.01 (0.98–1.04)||189||0.99 (0.95–1.04)||247||1.02 (0.98–1.06)||0.653|
|Brain||458||1.01 (0.98–1.04)||166||1.02 (0.97–1.07)||292||1.00 (0.96–1.03)||0.335|
|Endometrialc||146||1.02 (0.97–1.07)||73||1.02 (0.94–1.09)||73||1.02 (0.94–1.09)||0.791|
|Pancreas||1239||1.02 (1.00–1.03)||370||1.00 (0.96–1.03)||869||1.02 (1.00–1.05)b||0.314|
|Kidney||367||1.04 (1.01–1.08)b||99||1.07 (1.00–1.14)b||268||1.03 (0.99–1.08)||0.598|
|Rectum||168||1.03 (0.98–1.08)||49||0.99 (0.91–1.09)||119||1.04 (0.99–1.11)||0.385|
Joint associations for physical activity and BMI with all cancer mortality are presented in Table 4. Compared to the reference group of those who were active (reported more than never/rare MVPA) and non-obese (BMI<30 kg/m2), we found an increased risk of cancer mortality for those who were inactive and non-obese, (HR = 1.12; 95% CI 1.06–1.18) active and obese (1.16; 1.11–1.21) and inactive and obese (1.22; 1.13–1.32). Individuals who were obese, whether active or inactive, showed a 39% to over twofold statistically significant increased risk of death due cancers of the colon, liver, breast and endometrium compared to those who were active and non-obese.
Table 4. Joint associations between obesity (body mass index 30+ kg/mb) and moderate to vigorous intensity physical activity (MVPA, <1–7+ hr/wk) and cancer mortality in the NIH-AARP study population (N = 293,511)a
| ||Active/non-obese|| ||Inactive/non-obese|| ||Active/obese|| ||Inactive/ obese|
|Type of cancer death||No. of events||HR (ref.)||No. of events||HR (95% CI)||No. of events||HR (95% CI)||No. of events||HR (95% CI)|
|All cancers||10,001||1.00||1,758||1.12 (1.06–1.18)||2,476||1.16 (1.11–1.21)||766||1.22 (1.13–1.32)|
|Lymphocytic leukemia||90||1.00||12||0.95 (0.52–1.75)||18||0.97 (0.58–1.63)||8||1.60 (0.77–3.33)|
|Colon||639||1.00||116||1.22 (1.00–1.49)||199||1.39 (1.18–1.64)||82||2.01 (1.59–2.54)|
|Liver||231||1.00||41||1.12 (0.80–1.56)||84||1.62 (1.25–2.09)||41||2.64 (1.88–3.72)|
|Oral cavity and pharynx||112||1.00||32||1.43 (0.96–2.14)||23||0.97 (0.62–1.53)||6||0.73 (0.32–1.67)|
|Non–Hodgkin's lymphoma||406||1.00||71||1.28 (0.99–1.65)||118||1.35 (1.09–1.66)||33||1.38 (0.96–1.98)|
|Esophagus||297||1.00||63||1.30 (0.99–1.72)||106||1.63 (1.30–2.04)||25||1.28 (0.85–1.94)|
|Myeloma||226||1.00||40||1.36 (0.97–1.91)||54||1.14 (0.84–1.54)||21||1.67 (1.06–2.64)|
|Lung||3347||1.00||701||1.16 (1.06–1.26)||601||0.87 (0.80–0.95)||222||1.01 (0.88–1.16)|
|Myeloid/monocytic leukemia||262||1.00||31||0.87 (0.60–1.26)||60||1.08 (0.81–1.43)||23||1.55 (1.00–2.38)|
|Stomach||197||1.00||32||1.05 (0.72–1.53)||58||1.37 (1.01–1.84)||17||1.40 (0.85–2.31)|
|Ovarianb||264||1.00||37||1.05 (0.74–1.48)||62||1.05 (0.79–1.39)||24||1.45 (0.95–2.22)|
|Prostate||340||1.00||57||1.17 (0.88–1.56)||93||1.45 (1.15–1.82)||23||1.33 (0.87–2.04)|
|Bladder||235||1.00||35||0.98 (0.68–1.40)||59||1.19 (0.89–1.59)||17||1.20 (0.73–1.98)|
|Breastb||259||1.00||41||1.09 (0.78–1.52)||107||1.73 (1.37–2.19)||29||1.58 (1.07–2.35)|
|Brain||320||1.00||41||1.04 (0.75–1.45)||81||1.22 (0.95–1.56)||16||0.95 (0.57–1.58)|
|Endometrialb, c||73||1.00||11||1.03 (0.55–1.96)||50||2.48 (1.70–3.61)||12||2.04 (1.09–3.82)|
|Pancreas||880||1.00||115||0.91 (0.74–1.10)||210||1.12 (0.96–1.30)||34||0.64 (0.45–0.91)|
|Kidney||240||1.00||29||0.81 (0.55–1.19)||80||1.50 (1.16–1.94)||18||1.18 (0.72–1.91)|
|Rectum||123||1.00||12||0.66 (0.36–1.19)||27||0.99 (0.65–1.50)||6||0.77 (0.34–1.77)|
Restricting analyses to individuals without heart disease, diabetes and emphysema did not change results (data not shown). Excluding individuals with a BMI <15 kg/m2 or >50 also did not affect associations (data not shown). Stratification by age at questionnaire completion suggested stronger associations among older participants, but multiplicative interaction terms were not significant (data not shown).
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In our study population, higher MVPA before diagnosis was independently associated with a reduced risk of total cancer mortality. The observed inverse association was primarily driven by lower risks for death from cancers of the colon, liver and lung and non-Hodgkins lymphoma. Analyses of the joint effects of BMI and MVPA suggested lower risks of cancer death for active, non-obese individuals for various cancer sites.
Few studies report on physical activity and cancer mortality. A previous study in this cohort with less follow-up and fewer deaths found that those reporting >7 hr of MVPA each week had a 17% lower risk of cancer mortality (0.83; 0.74–0.93) compared to individuals reporting no MVPA. In a large Taiwanese cohort, researchers found a lower overall cancer mortality risk (0.83; 0.77–0.90) comparing those with higher leisure time physical activity (∼20 metabolic equivalent hours per week) to inactive individuals. In this Taiwanese study, significant inverse associations were observed for deaths due to colon and rectum cancer, liver cancer and lung cancer, while the association was not significant for breast cancer mortality. Another study using a treadmill test to assess fitness and a questionnaire to report physical activity levels showed that fitness and reported physical activity each were associated with lower overall cancer mortality among men, while among women there was a suggested but not significant association. However, that study had a small number of female deaths due to cancer (n = 44), possibly contributing to the lack of statistically significant findings.
In this cohort, previous physical activity analyses focused largely on cancer incidence, reporting inverse associations for liver, renal cell, breast, endometrial and colon cancers.[17, 22-25] Another study in this cohort on the joint effects of physical activity and adiposity on all-cause mortality also showed independent effects of each on mortality risk. Our finding on the joint association between physical activity and body mass index with all-cancer mortality adds to the published literature in this cohort and is consistent with a previous publication in a large cohort of women reporting independent and joint effects of physical activity and BMI on reduced all-cancer mortality risk.
To our knowledge, previous studies have not comprehensively reported on physical activity and risk of death from individual cancers. A growing body of energy balance survivorship literature was summarized in a recent review of 27 observational studies on physical activity among cancer survivors, reporting that physical activity was associated with lower rates of all-cause mortality and cancer-specific mortality for breast and colon cancers. A recent forum on obesity, energy balance and cancer survival also highlighted protective effects among those who were normal weight and active for breast and colon cancer-specific mortality among survivors. Our observed inverse association between physical activity and colon cancer mortality is consistent with these findings. A study in the Women's Health Initiative reported an association between pre-diagnosis moderate intensity activity and breast cancer death, but similar to our findings, other studies have shown no association between pre-diagnosis physical activity and breast cancer death.[20, 28, 29] These conflicting findings could be due to differences in physical activity questionnaires, differences in time periods from measurement to diagnosis and follow up time or differences in study populations, such as the age at diagnosis or the percentage who reported menopausal hormone therapy usage. Literature on physical activity and mortality from other specific cancer sites is limited, although the above-mentioned review summarized limited evidence of an inverse association for prostate cancer mortality and no association for ovarian cancer mortality. Also, a previous study on pre-diagnosis physical activity and endometrial cancer mortality in this cohort also showed no association. Our observed positive association between MVPA and kidney cancer death contrasts with previous findings on MVPA cancer incidence in this cohort, which showed an inverse association between physical activity and renal cancer, which accounts for about 80% of kidney cancers. However, other prospective cohort studies have shown no association between physical activity and renal cancer risk[31-33] and both risk factors and potential mechanisms related to physical activity may be different for incidence than for cancer mortality. A recent meta-analysis showed protective associations between leisure-time physical activity and lung cancer risk, and the high fatality of lung cancer may translate into similarities between risk factors for incidence and mortality. Published findings on physical activity and liver cancer are limited, although a previous analysis in this cohort showed an inverse association between physical activity and risk of developing liver cancer.
Mechanisms explaining the association between physical activity and mortality have been more widely studied in relation to cancer incidence. Review papers on mechanisms by which physical activity may affect cancer risk cite metabolic effects of high physical activity including lower body mass index, lower circulating sex hormones and insulin levels and possibly effects on inflammation or the immune system.[35, 36] These proposed mechanisms likely differ by specific cancer site. Some exercise intervention studies among survivors show improvements in circulating insulin levels and biomarkers related to cancer progression and recurrence.[37, 38] It is also possible that individuals who are active before diagnosis might have healthful habits (e.g., exercise) that are easier to maintain after diagnosis.
Strengths of our study include the large, prospective nature of the cohort and sufficient follow-up time. Other strengths include the objective endpoint (mortality) as well as a comprehensive range of cancer deaths, allowing examination of site-specific cancers. Detailed covariate information allowed us to examine effect modification by other risk factors such as BMI, smoking and diabetes.
Limitations of our study include measurement errors associated with self-report of physical activity. Although we had only a single measure of physical activity, we asked about physical activity in the past 10 years, attempting to reflect individuals' usual activity levels over time. Also, we lacked information on physical activity levels after cancer diagnosis, which may differ from pre-diagnosis levels. We adjusted for known confounders but we cannot eliminate the possibility that results were influenced by other lifestyle factors associated with physical activity, including better health maintenance and health insurance coverage. Lastly, we cannot rule out a possibility of observing associations by chance due to multiple comparisons.
Notably, the inverse association between MVPA and cancer mortality risk became significant with 1 hr or more of physical activity per week, and the magnitude of the protective association increased only slightly with more MVPA, as shown by similar point estimates in the higher MVPA categories. This exploratory analysis was the first to examine MVPA and site-specific cancer mortality and was intended to generate new hypotheses. In particular, inverse associations observed with MVPA and deaths from colon, liver and lung cancers should be further explored. The observed positive association with kidney cancer death also merits investigation. In addition, future research should isolate associations with moderate versus vigorous activities, post-diagnosis physical activity and whether changes in activity levels from pre to post-diagnosis affect cancer-specific mortality.
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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, Atlanta, Georgia. Cancer incidence data from California were collected by the California Cancer Registry, California Department of Public Health's Cancer Surveillance and Research Branch, Sacramento, California. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, Lansing, Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (Miami, Florida) under contract with the Florida Department of Health, Tallahassee, Florida. 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 Health Sciences Center School of Public Health, New Orleans, Louisiana. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health, Trenton, New Jersey. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry, Raleigh, North Carolina. 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, Phoenix, Arizona. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas. Cancer incidence data from Nevada were collected by the Nevada Central Cancer Registry, State Health Division, State of Nevada Department of Health and Human Services, Las Vegas, Nevada. The authors are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. The authors also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcomes ascertainment and management and Leslie Carroll at Information Management Services for data support and analysis.