Healthy Eating and Risk for Pancreatic Cancer
Healthy Eating and Risk for Pancreatic Cancer
The NIH–AARP Diet and Health Study has been described previously. Men and women aged 50 to 71 years who were AARP members were recruited by mailed questionnaire returned in the period from 1995 to 1996. All participants were residents in one of six US states (California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania) or two metropolitan areas (Atlanta, Georgia, or Detroit, Michigan) at baseline. Of the 566 399 participants who satisfactorily completed the baseline questionnaire, we excluded those whose questionnaires were completed by proxy (n = 15 760), those with any prevalent registry-confirmed cancer (except for nonmelanoma skin cancer) at baseline (n = 8587), and participants who moved out of the study area or died at or before processing of the baseline questionnaire (n = 24). We also excluded participants for whom calculated total energy intake exceeded more than two sex-specific interquartile range amounts above the 75th or below the 25th percentile on a logarithmic scale (n = 4810). Our final analytic cohort consisted of 537 218 persons (n = 316 670 men; n = 220 548 women). The NIH–AARP Diet and Health study was approved by the Special Studies Institutional Review Board of the US National Cancer Institute (NCI), and all participants gave informed consent by virtue of completing and returning the questionnaire.
At baseline, participants completed a 124-item food frequency questionnaire (FFQ) developed at the NCI. The FFQ queried the usual frequency of foods and beverages consumed over the previous 12 months (10 categories ranging from never to ≥6 times per day for beverages and never to ≥2 times per day for foods), and usual portion size (less than three-quarters cup, three-quarters to 1 cup, ≥1 cup). Responses to the FFQ were validated for foods and nutrients in a calibration study based on two nonconsecutive telephone-administered 24-hour dietary recalls within a year of the baseline questionnaire (mean days apart = 25) from a stratified random sample of the NIH–AARP participants (n = 2053).
The HEI-2005 was developed jointly by the NCI and the US Department of Agriculture to serve as a measure of overall diet compliance with the 2005 Dietary Guidelines for Americans. To calculate the HEI-2005 score, dietary data from the FFQ were merged with the MyPyramid Equivalents Database (MPED) (version 1.0) to generate pyramid equivalents for the 12 components. The MPED disaggregates reported food intakes into component ingredients and combines like ingredients into meaningful groups to generate amounts of each MyPyramid group and subgroup consumed.
Scoring criteria for the HEI-2005 are summarized in Table 1. In short, for the nine "adequacy" components where there was a recommended minimum intake, the highest score was assigned for meeting dietary guidelines. These "adequacy" components included total fruit, nonjuice fruit, total vegetables, dark-green and orange vegetables and legumes, total grains, whole grains, milk products (including soy), healthy oils, and meat and beans (including meat, poultry, fish, and legumes). Only the lowest fat portions of milk and meat were included in respective components. Consumption less than the recommended amount was scored in a linear, prorated fashion. An additional three "moderation" components with maximum recommended intakes (saturated fat, sodium and calories from solid fat, alcohol and added sugars) were reverse scored, whereby lower consumption levels were awarded higher scores. All scores were expressed per 1000 calories to account for differences in energy intake. The HEI-2005 score describes 0 as no guidelines met and 100 as all guidelines met.
Incident cancers were ascertained by linking participants to the eight state registries of study enrollment and three additional states (Arizona, Nevada, and Texas). Cancer registry case ascertainment is estimated to be about 90% complete for this cohort. Vital status was verified annually by linkage to the Social Security Administration Death Master File and to the US National Death Index, as well as by cancer registry. We included incident exocrine pancreatic cancer case subjects (International Classification of Diseases for Oncology, Third Edition, codes C250–C259) diagnosed during the follow-up period though December 31, 2006, or identified as pancreatic cancer deaths in the US National Death Index. Endocrine pancreatic tumors, sarcomas, and lymphomas (histology types 8150, 8551, 8153, 8155, and 8240) were not counted because the etiologies of these cancers are thought to be different.
We classified individuals into sex-stratified quintiles of HEI-2005 score because previous studies have shown differences in dietary patterns and pancreatic cancer by sex. We used Cox proportional hazards regression with age as the underlying time metric to test associations between the HEI-2005 score and pancreatic cancer risk. We calculated follow-up time from date of baseline questionnaire to pancreatic cancer diagnosis, death, move from study area, or end of follow-up, whichever came first. The proportional hazards assumption was evaluated by modeling interaction terms of the continuous HEI-2005 score with follow-up time. A cancer diagnosis other than exocrine pancreatic cancer was not treated as a censoring event. We considered all variables in Table 2 as potential confounders during model building and created parsimonious models that included variables that were putative risk factors or changed the log hazard ratio (HR) by more than 10%. Final models were adjusted for smoking status at baseline (never, quit >10 years ago, 5–9 years ago, 1–4 years ago, <1 year ago or current ≤20 cigarettes per day, quit <1 year ago or current >20 cigarettes per day), self-reported diabetes history (yes/no), body mass index (BMI) (15 to <18.5, 18.5 to <25, 25 to <30, 30 to ≤50kg/m, or missing), and sex (for sex-combined models).
In addition to our main hypothesis that there would be a reduced risk comparing extreme HEI-2005 scores, to test whether there was a linear trend, we assigned an ordinal score to the sex-specific median value of each quintile and treated the variable as linear. We also performed continuous analyses scaling the score by the interquartile range. To test whether a linear assumption was appropriate, we performed an analysis allowing for a natural spline and also assessed martingale residuals. Both tests indicated that a linear model was sufficient.
We performed sensitivity analyses excluding those who had less than 4 years of follow-up to assess whether results were influenced by undetected disease. We also tested whether the association was driven by specific components of the HEI-2005 score by creating a single model with all 12 components. A previous NIH–AARP study showed that individuals consuming 3 or more drinks per day had an increased risk of pancreatic cancer. Therefore, we conducted two sensitivity analyses, first excluding those who consumed 3 or more drinks per day and secondly summing the HEI-2005 score without alcohol, while separately adjusting for alcohol intake. We assessed effect modification by sex, diabetes, smoking (never, former, current), and BMI (18.5 to <25 and ≥25.0kg/m) with stratified analyses and consideration of interactions using the Wald test. Given that 93% of our sample was non-Hispanic white, we were unable to analyze other racial or ethnic groups separately. We used SAS version 9.2 for all analyses (SAS Institute, Cary NC), and all P values were two-sided, with those less than .05 considered statistically significant.
Methods
Study Population
The NIH–AARP Diet and Health Study has been described previously. Men and women aged 50 to 71 years who were AARP members were recruited by mailed questionnaire returned in the period from 1995 to 1996. All participants were residents in one of six US states (California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania) or two metropolitan areas (Atlanta, Georgia, or Detroit, Michigan) at baseline. Of the 566 399 participants who satisfactorily completed the baseline questionnaire, we excluded those whose questionnaires were completed by proxy (n = 15 760), those with any prevalent registry-confirmed cancer (except for nonmelanoma skin cancer) at baseline (n = 8587), and participants who moved out of the study area or died at or before processing of the baseline questionnaire (n = 24). We also excluded participants for whom calculated total energy intake exceeded more than two sex-specific interquartile range amounts above the 75th or below the 25th percentile on a logarithmic scale (n = 4810). Our final analytic cohort consisted of 537 218 persons (n = 316 670 men; n = 220 548 women). The NIH–AARP Diet and Health study was approved by the Special Studies Institutional Review Board of the US National Cancer Institute (NCI), and all participants gave informed consent by virtue of completing and returning the questionnaire.
Dietary Assessment
At baseline, participants completed a 124-item food frequency questionnaire (FFQ) developed at the NCI. The FFQ queried the usual frequency of foods and beverages consumed over the previous 12 months (10 categories ranging from never to ≥6 times per day for beverages and never to ≥2 times per day for foods), and usual portion size (less than three-quarters cup, three-quarters to 1 cup, ≥1 cup). Responses to the FFQ were validated for foods and nutrients in a calibration study based on two nonconsecutive telephone-administered 24-hour dietary recalls within a year of the baseline questionnaire (mean days apart = 25) from a stratified random sample of the NIH–AARP participants (n = 2053).
The HEI-2005 was developed jointly by the NCI and the US Department of Agriculture to serve as a measure of overall diet compliance with the 2005 Dietary Guidelines for Americans. To calculate the HEI-2005 score, dietary data from the FFQ were merged with the MyPyramid Equivalents Database (MPED) (version 1.0) to generate pyramid equivalents for the 12 components. The MPED disaggregates reported food intakes into component ingredients and combines like ingredients into meaningful groups to generate amounts of each MyPyramid group and subgroup consumed.
Scoring criteria for the HEI-2005 are summarized in Table 1. In short, for the nine "adequacy" components where there was a recommended minimum intake, the highest score was assigned for meeting dietary guidelines. These "adequacy" components included total fruit, nonjuice fruit, total vegetables, dark-green and orange vegetables and legumes, total grains, whole grains, milk products (including soy), healthy oils, and meat and beans (including meat, poultry, fish, and legumes). Only the lowest fat portions of milk and meat were included in respective components. Consumption less than the recommended amount was scored in a linear, prorated fashion. An additional three "moderation" components with maximum recommended intakes (saturated fat, sodium and calories from solid fat, alcohol and added sugars) were reverse scored, whereby lower consumption levels were awarded higher scores. All scores were expressed per 1000 calories to account for differences in energy intake. The HEI-2005 score describes 0 as no guidelines met and 100 as all guidelines met.
Identification of Pancreatic Cancer Case Subjects
Incident cancers were ascertained by linking participants to the eight state registries of study enrollment and three additional states (Arizona, Nevada, and Texas). Cancer registry case ascertainment is estimated to be about 90% complete for this cohort. Vital status was verified annually by linkage to the Social Security Administration Death Master File and to the US National Death Index, as well as by cancer registry. We included incident exocrine pancreatic cancer case subjects (International Classification of Diseases for Oncology, Third Edition, codes C250–C259) diagnosed during the follow-up period though December 31, 2006, or identified as pancreatic cancer deaths in the US National Death Index. Endocrine pancreatic tumors, sarcomas, and lymphomas (histology types 8150, 8551, 8153, 8155, and 8240) were not counted because the etiologies of these cancers are thought to be different.
Statistical Analysis
We classified individuals into sex-stratified quintiles of HEI-2005 score because previous studies have shown differences in dietary patterns and pancreatic cancer by sex. We used Cox proportional hazards regression with age as the underlying time metric to test associations between the HEI-2005 score and pancreatic cancer risk. We calculated follow-up time from date of baseline questionnaire to pancreatic cancer diagnosis, death, move from study area, or end of follow-up, whichever came first. The proportional hazards assumption was evaluated by modeling interaction terms of the continuous HEI-2005 score with follow-up time. A cancer diagnosis other than exocrine pancreatic cancer was not treated as a censoring event. We considered all variables in Table 2 as potential confounders during model building and created parsimonious models that included variables that were putative risk factors or changed the log hazard ratio (HR) by more than 10%. Final models were adjusted for smoking status at baseline (never, quit >10 years ago, 5–9 years ago, 1–4 years ago, <1 year ago or current ≤20 cigarettes per day, quit <1 year ago or current >20 cigarettes per day), self-reported diabetes history (yes/no), body mass index (BMI) (15 to <18.5, 18.5 to <25, 25 to <30, 30 to ≤50kg/m, or missing), and sex (for sex-combined models).
In addition to our main hypothesis that there would be a reduced risk comparing extreme HEI-2005 scores, to test whether there was a linear trend, we assigned an ordinal score to the sex-specific median value of each quintile and treated the variable as linear. We also performed continuous analyses scaling the score by the interquartile range. To test whether a linear assumption was appropriate, we performed an analysis allowing for a natural spline and also assessed martingale residuals. Both tests indicated that a linear model was sufficient.
We performed sensitivity analyses excluding those who had less than 4 years of follow-up to assess whether results were influenced by undetected disease. We also tested whether the association was driven by specific components of the HEI-2005 score by creating a single model with all 12 components. A previous NIH–AARP study showed that individuals consuming 3 or more drinks per day had an increased risk of pancreatic cancer. Therefore, we conducted two sensitivity analyses, first excluding those who consumed 3 or more drinks per day and secondly summing the HEI-2005 score without alcohol, while separately adjusting for alcohol intake. We assessed effect modification by sex, diabetes, smoking (never, former, current), and BMI (18.5 to <25 and ≥25.0kg/m) with stratified analyses and consideration of interactions using the Wald test. Given that 93% of our sample was non-Hispanic white, we were unable to analyze other racial or ethnic groups separately. We used SAS version 9.2 for all analyses (SAS Institute, Cary NC), and all P values were two-sided, with those less than .05 considered statistically significant.
