Diet Quality and Subsequent Incidence of Upper Gastrointestinal Cancers: Results from the Golestan Cohort Study

Background: Recent evidence suggests overall diet quality, as assessed by dietary scores, may play a role in the development of upper gastrointestinal (UGI) cancers. However, the existing dietary scores are derived from high-income countries with different dietary habits than regions with the highest burden of UGI cancers, where limited data is available. This study aimed to investigate the association between overall diet quality and risk of esophageal and stomach cancers in a high-risk region for UGI cancers. Methods: We recruited 50045 individuals aged 40-75 between 2004-2008 from northeastern Iran and followed them annually through July 2020. Data on demographics, diet, and various exposures were collected using validated questionnaires. Diet quality was assessed by calculating the Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), Alternative Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and World Cancer Research Fund–American Institute for Cancer Research (WCRF-AICR) scores. Results: During an average 12 years of follow-up, 359 participants developed esophageal cancer and 358 developed stomach cancer. After adjustments, each standard deviation increase in baseline dietary scores was associated with up to 12% reduction in esophageal cancer risk and up to 17% reduction in stomach cancer risk. Esophageal cancer showed stronger inverse associations with adherence to AMED (HRQ4-vs-Q1=0.69 (0.49–0.98), P-trend=0.038). Stomach cancer showed stronger inverse correlation with WCRF-AICR (HRQ4-vs-Q1=0.58 (0.41–0.83), P-trend=0.004), and DASH (HRC4-vs-C1=0.72 (0.54–0.96), P-trend=0.041). These associations were comparable across different population subgroups. We did not observe significant associations between HEI and AHEI scores and UGI cancers in this population. Conclusion: Despite the differences in consuming individual food groups, adherence to the available dietary recommendations (derived from high-income countries) was associated with lower risk for subsequent esophageal and gastric cancers in this high-risk population. Educating the public to have a healthy eating pattern might be an effective strategy towards prevention of UGI cancers in high-risk regions.


HEI-2015
The HEI-2015 includes 13 components for a total of 100 points based on the 2015 Dietary Guidelines for Americans 7 , including 9 adequacy components: total fruit (including fruit juice); whole fruit; total vegetables; greens and beans (including dark green vegetables and legumes); whole grains; dairy; total protein foods [includes meat and poultry (lean fraction), eggs, seafood, nuts, seeds, soy and legumes]; seafood and plant proteins [including seafood, nuts, seeds, soy and legumes]; fatty acids [ratio of polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs)] (Table S2); and four moderation components: SFAs, refined grains, sodium, and added sugars (Table S2).The components were calculated per 1000 kcal/d (energy density model).

AHEI-2010
The AHEI-2010 includes 11 components for a total of 110 points [8][9][10] .The AHEI-2010 includes fruits, vegetables, whole grains, red and processed meat, nuts and legumes, trans fats, omega-3 fatty acids, PUFAs, sugary sweetened beverages (SSB) and fruit juice, sodium, and alcohol (Table S2).The AHEI-2010 is similar to HEI-2015; however, potatoes are not included in the vegetable group in this score.Also, the AHEI-2010 uses an absolute intake method instead of a nutrient density method 9 .SSBs were defined as any beverages containing a caloric sweetener, even if added after purchase 11 .Therefore, we included sweet tea if it contained approximately one half (or more) of the sugar and calories of regular sodas 11 .

AMED
The AMED includes nine components for a total of nine points, based on the Mediterranean diet 12 : all vegetables (excluding potatoes), all fruits (including juice), nuts, legumes, fish, whole grains, MUFA to SFA ratio, red and processed meat, and alcohol.We applied one point where reported red and processed meat consumption was less than the sex-specific median.For other components, intakes above the sex-specific median of the study subjects received one point.All other intakes received 0 points (Table S2).

DASH-Fung score
The DASH score created by Fung includes eight components for a total of 40 points: seven food groups and one nutrient 13 .Scores are based on sex-specific quintiles in the population.The highest quintile of intake for fruits, vegetables, low-fat dairy, whole grains, nuts and legumes each received five points, and the highest quintile of intake for red and processed meat, SSBs, and sodium each received one point (Table S2).

WCRF-AICR score
The WCRF/AICR score includes seven dietary components: energy dense foods which cause weight gain 14 , fruits and vegetables, red and processed meat, alcohol, sugary drinks, fiber, and sodium; plus nondietary components associated with cancer risk including physical activity, body fatness, and breastfeeding 15 .However, we only calculated the dietary components in this study, to allow for comparability with the other dietonly scores.Energy density was calculated as energy from all solid and semi-solid foods divided by the weights (g) of these foods.Drinks (including water, tea, green tea, juice, soft drinks, alcoholic drinks and milk) were not included in the calculation of energy density 14 .For each component, participants who met the official recommendation received one point, those who met an intermediate recommendation received one-half of a point, and those who met neither recommendation received zero points 15 (Table S2).
Alcohol was queried on the demographic baseline questionnaire.Since alcohol intake is not common in this population (4%), all participants received a zero for it in each dietary score.Also, no item in the FFQ was whole-grain, because they are not consumed by this population, so all respondents received a zero for whole grains.We did not modify the scores and did not delete these components, so that we could compare the scores from this population with others.

Table S1 .
D, Vergnaud AC, Peeters PH, van Gils CH, Chan DS, Ferrari P, et al.Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer?Results from the EPIC study.Am J Clin Nutr.2012;96(1):150-63.doi: 10.3945/ajcn.111.031674.Assigning foods queried in the food frequency questionnaire of the Golestan Cohort Study to food groups Total meat (including organ meats and cured meats); poultry; seafood; eggs; nuts and seeds; soy; and beans and peas Seafood and Plant Proteins Seafoods, nuts, seeds, soy products, and beans and peas Greens and Beans Dark green vegetables, and any beans and peas (legumes) Red/processed meat Unprocessed red meat (beef or lamb, hamburger), liver, chicken liver; and processed red meat (sausage) Nuts Walnuts, peanuts, mixed nuts Legumes White bean, red bean, pinto bean, chickpea, split pea, soy bean, and lentil Fish Stellate sturgeon, Carp, Smoked fish, Salted fish, and tuna Sugary sweetened beverages Soft drink, Commercial juice, sweet beverage, sweet tea

Table S2 .
Components and minimum and maximum criteria for dietary scores

Table S3 .
Sex-stratified analysis to assess the association between dietary scores and incident upper gastrointestinal cancers in the Golestan Cohort Study.

Table S4 .
Socioeconomic-stratified analysis to assess the association between dietary scores and incident upper gastrointestinal cancers in the Golestan Cohort Study.World Cancer Research Fund/American Institute for Cancer Research index N: number; Q: quartile; HEI: Healthy Eating Index 2015; AHEI: Alternative Healthy Eating Index 2010; AMED: Alternate Mediterranean Diet; DASH: Dietary Approaches to Stop Hypertension; WCRF/AICR: