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Chinese Journal of Cancer Research logoLink to Chinese Journal of Cancer Research
. 2024 Feb 29;36(1):36–45. doi: 10.21147/j.issn.1000-9604.2024.01.04

Plant-based dietary patterns and risk of esophageal cancer: A prospective cohort study spanning 17 years

Xiaorui Zhang 1, Feifan He 2, Jiayue Li 2, Ru Chen 2, Xinqing Li 3, Li Li 2, Fen Liu 1,*, Shaoming Wang 2,*, Wenqiang Wei 2,*
PMCID: PMC10915634  PMID: 38455370

Abstract

Objective

Plant-based diets have multiple health benefits for cancers; however, little is known about the association between plant-based dietary patterns and esophageal cancer (EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.

Methods

We performed endoscopic screening for 15,709 participants aged 40−69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) of EC across 3 plant-based diet indices and further stratified the analysis by subgroups.

Results

The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365 person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50 (95% CI, 0.32−0.77) for hPDI. In addition, the HR per 10-point increase in the hPDI score was 0.42 (95% CI, 0.27−0.66) for ECs. Conversely, uPDI was positively associated with the risk of EC, and the HR was 1.80 (95% CI, 1.16−2.82). The HR per 10-point increase in the uPDI score was 1.90 (95% CI, 1.26−2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.

Conclusions

A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

Keywords: Esophageal cancer, diet, dietary pattern, epidemiology, nutrition, prospective cohort study

Introduction

Esophageal cancer (EC) is the eighth most frequently diagnosed cancer worldwide and ranks as the sixth leading cause of cancer-related deaths, with approximately 604,100 new cases and 544,100 deaths (1). An overwhelming 53.7% of all EC cases globally are reported in China, with estimates of 324,422 new cases and 301,135 deaths in 2020 (2).

Diet is a major modifiable risk factor for EC. The esophageal mucosa is in direct contact with ingested food, and its physiology is closely influenced by hormonal and neural connections, which are affected by the quality, quantity, and timing of meals. Plant-based diets such as vegetarian or vegan diets are significantly associated with a decreased risk of total cancer (3). Nevertheless, epidemiological evidence on the association between plant-based diets and EC is scarce, particularly in Chinese populations, whose dietary patterns differ markedly from those of Western countries.

Plant-based diets represent dietary approaches that emphasize the consumption of foods derived from plants while restricting or excluding certain or all animal-based products (4). Epidemiological studies have provided evidence supporting the advantageous effects of specific plant-based foods, such as whole grains and fibre, in reducing EC risk (5,6). However, it is essential to note that not all plant foods are beneficial, as certain items, such as pickled vegetables, may be harmful to ECs (7). To better account for the healthiness and quality of plant-based foods in previous studies, plant-based diet indices (PDIs) were proposed. PDIs encompass the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) (8,9). Greater hPDI scores have been inversely associated with cardiovascular diseases (10), diabetes (8) and certain cancers (11,12), while higher uPDI scores have shown adverse associations with the incidence of these diseases. The original PDIs were type 2 diabetes (T2D)-specific indices that used existing knowledge of food associations with T2D to differentiate between healthy and less healthy plant foods, rather than being tailored specifically for cancer or EC research. Thus, plant foods that did not exhibit a clear and unidirectional relationship with these health outcomes, such as alcoholic beverages, were deliberately excluded from the indices (8). However, strong evidence related to alcohol consumption indicates an increased risk of esophageal squamous cell carcinoma (ESCC) (13). In the study of the effects of PDIs on cognitive function in the Chinese population, the Chinese culinary attribute was introduced for the first time in traditional PDIs, providing an exploratory refinement. These adjustments involved restructuring the original PDIs framework, including garlic and pickled vegetables, and fine-tuning the scoring methodology (14,15). Currently, the association between plant-based diets and EC incidence has been examined in only one study within U.S. cohorts, which may not reflect the distribution of EC histological subtypes in China (16). Hence, we explored the associations of PDIs with the dietary habits of high-risk sites of EC in China by referring to the foods in the original PDIs.

The aim of the present study was to prospectively examine the associations between three predefined indices of plant-based dietary patterns and the risk of EC using a cohort from high-risk sites of the National Cancer Early Detection and Treatment Project (NCEDTP) (Linzhou and Feicheng) in China.

Materials and methods

Study population

This study was carried out at two high-risk sites in the NCEDTP (Linzhou and Feicheng) (17). All residents aged between 40−69 years were the target population and 31,826 participants were included. This age group was chosen based on early research, which indicated that the annual age-adjusted mortality rates for EC among individuals aged 40−69 years were 100−150 times greater than the rates adjusted for U.S. whites (18). Individuals who declined to undergo endoscopic screening were excluded. The participation rate in the target population was 49.36%, enrolling a total of 15,709 individuals from January 2005 to December 2009. Participants completed questionnaires about demographic information, height, weight, lifestyle factors, previous medical history of digestive system diseases, and family history of cancer. The study was approved by the Institutional Review Board of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 20/386-2582).

Surveillance of EC

All patients completed baseline surveys during the period spanning from January 2005 to December 2009. Then, they received follow-up through monthly phone calls, home visits every three months, reviews of medical records, and annual assessments of cancer registries. We continued follow-up until the occurrence of EC, death, or the end of follow-up (31 December 2022), whichever occurred first. For this analysis, we excluded participants who were diagnosed with upper gastrointestinal cancer before or at baseline, had an unclear diagnosis, or whose information was missing from the questionnaire. We used the tenth edition of the International Classification of Diseases (ICD-10) for case identification: esophageal cancer (C15.0−C15.5, C15.8−C15.9). A total of 15,184 participants are included in the final analysis (Figure 1).

Figure 1.

Figure 1

Flowchart of study population selection.

Dietary assessment

The trained investigators performed a face-to-face survey using standard questionnaires, and participants answered the questions by themselves. The dietary section of the questionnaire included 15 commonly consumed food groups at high-risk sites for EC in China: fresh vegetables, fresh fruits, legumes, dried fruits and vegetables, staple foods, spring onions, garlic, tea, pickled vegetables, fried food, hot food, mildewed food, dairy products, eggs, meat, alcoholic beverages, and tea. The definitions of these food groups are reported in the (Supplementary Table S1). The questionnaire recorded the intake frequency and duration of time as “times/week”, “times/month”, “times/year” and “duration of time” for most food groups, except for the consumption of tea and alcoholic beverages. The questionnaire recorded the frequency of intake of tea and alcoholic beverages as “yes” or “no”.

Table S1. Definition of PDI, hPDI and uPDI.

Variables PDI hPDI uPDI
PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index. Positive, positive scores [quintile (Q) 1=1, Q2=2, Q3=3, Q4=4, Q5=5]; Reverse, reverse scores (Q5=1, Q4=2, Q3=3, Q2=4, Q1=5). a, mixed grains, mainly consisting of corn and wheat; b, mainly include fried cake, deep-fried dough sticks; c, mainly include hot soup, hot noodles; d, mainly include mildewed staple food; e, mainly include alcoholic beverages, beer, fruit wine; f, mainly include pork, beef, rabbit, chicken, or duck.
Plant food groups
 Healthy
  Fresh vegetable Positive Positive Reverse
  Fresh fruit Positive Positive Reverse
  Legumes Positive Positive Reverse
  Dried fruit and vegetable Positive Positive Reverse
  Staple fooda Positive Positive Reverse
  Spring onion, garlic Positive Positive Reverse
  Tea Positive Positive Reverse
 Less healthy
  Pickled vegetable Positive Reverse Positive
  Fried foodb Positive Reverse Positive
  Hot foodc Positive Reverse Positive
  Mildewed foodd Positive Reverse Positive
  Alcoholic beveragee Positive Reverse Positive
Animal food groups
  Dairy products Reverse Reverse Reverse
  Egg Reverse Reverse Reverse
  Meatf Reverse Reverse Reverse

We assessed the plant-based dietary pattern by calculating three plant-based diet indices (PDI, hPDI, and uPDI), an adapted approach used in previous studies (8,14). The included food groups covered the most common food consumed in the daily diet at high-risk sites in China from 2005 to 2009. We incorporated a total of 15 food groups for evaluation; these groups were differentially associated with a set of health outcomes (19,20). The healthy plant foods consisted of fresh vegetables, fresh fruits, legumes, dried fruits and vegetables, staple foods, spring onions, garlic, and tea. The less healthy plant foods included pickled vegetables, fried food, hot food, mildewed food, and alcoholic beverages. The animal foods were represented by dairy products, eggs, and meat. The categorization of the dietary assessments is determined in advance of the study (Supplementary Table S1).

We scored three plant-based diet indices according to intake frequency. Although servings or quintiles of intake are commonly used, using a nonquantitative food frequency questionnaire to assess dietary patterns has been demonstrated to be reliable and valid in some studies (21-23). In addition, previous studies have shown that the frequency of intake is more important than the portion size for distinguishing between high and low consumption of fruits and vegetables (24). The average number of intakes was calculated according to the intake frequency and duration. The frequency of intake was converted to “almost every day”, “≥1 time/week”, “≥1 time/month”, “occasionally”, or “rarely or never”. The participants’ scores in the study followed a distinct pattern: the highest frequency of consumption for any plant food group received a score of 5, whereas the lowest frequency of consumption received a score of 1. In contrast, the scoring for the animal food group was the opposite: the highest frequency of consumption received a score of 1, while the lowest frequency of consumption received a score of 5. Tea and alcoholic beverages were coded as “yes” or “no” and were assigned scores of 1 and 5, depending on the specific indices used in the study. More details on constructing and scoring PDIs can be found in Supplementary Table S2. For the PDI, higher scores were assigned to any plant food group, whereas reverse scores were assigned to animal food groups. For the hPDI, higher scores were given to healthy plant food groups, while reverse scores were assigned to less healthy plant food groups and animal food groups. Conversely, for the uPDI, higher scores were assigned to less healthy plant food groups, and reverse scores were given to healthy plant food groups and animal food groups. The 15 food group scores for an individual were summed to obtain the indices, with a theoretical range of 15−75.

Table S2. Plant-based diet indices scoring.

Food N (times/week) Frequency PDI hPDI uPDI
PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index; N=(W*4+M+Y/12)*D/48; W, times/week; M, times/month; Y, times/year; D, duration of time.
Plant food group
 Healthy
  Fresh vegetable N≥7.00 Almost everyday 5 5 1
1.00≤N<7.00 ≥1 time/week 4 4 2
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 2 4
N=0 Rarely or never 1 1 5
  Fresh fruit N≥7.00 Almost everyday 5 5 1
1.00≤N<7.00 ≥1 time/week 4 4 2
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 2 4
N=0 Rarely or never 1 1 5
  Legumes N≥7.00 Almost everyday 5 5 1
1.00≤N<7.00 ≥1 time/week 4 4 2
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 2 4
N=0 Rarely or never 1 1 5
  Dried fruits and vegetables N≥7.00 Almost everyday 5 5 1
1.00≤N<7.00 ≥1 time/week 4 4 2
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 2 4
N=0 Rarely or never 1 1 5
  Staple food N≥7.00 Almost everyday 5 5 1
1.00≤N<7.00 ≥1 time/week 4 4 2
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 2 4
N=0 Rarely or never 1 1 5
  Spring onion, garlic N≥7.00 Almost everyday 5 5 1
1.00≤N<7.00 ≥1 time/week 4 4 2
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 2 4
N=0 Rarely or never 1 1 5
  Drink tea Yes Yes 5 5 1
No No 1 1 5
 Less healthy
  Pickled vegetable N≥7.00 Almost everyday 5 1 5
1.00≤N<7.00 ≥1 time/week 4 2 4
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 4 2
N=0 Rarely or never 1 5 1
  Fried food N≥7.00 Almost everyday 5 1 5
1.00≤N<7.00 ≥1 time/week 4 2 4
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 4 2
N=0 Rarely or never 1 5 1
  Hot food N≥7.00 Almost everyday 5 1 5
1.00≤N<7.00 ≥1 time/week 4 2 4
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 4 2
N=0 Rarely or never 1 5 1
  Mildewed food N≥7.00 Almost everyday 5 1 5
1.00≤N<7.00 ≥1 time/week 4 2 4
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 2 4 2
N=0 Rarely or never 1 5 1
  Alcoholic beverage Yes Yes 5 1 5
No No 1 5 1
Animal food groups
 Meat, egg, dairy products N≥7.00 Almost everyday 1 1 1
1.00≤N<7.00 ≥1 time/week 2 2 2
0.25≤N<1.00 ≥1 time/month 3 3 3
0<N<0.21 Occasionally 4 4 4
N=0 Rarely or never 5 5 5

Assessment of covariates

We assessed demographic characteristics, socioeconomic status, lifestyle factors, and medical status. The covariates included age (year), gender (male or female), marital status (married, unmarried, divorced, widowed), educational status (no education, elementary school, middle school and above), number of family members, annual income (CNY per person), smoking status (yes or no), prior history of digestive diseases (yes or no), and family history of cancer (yes or no). Additionally, we calculated body mass index (BMI) based on height and weight.

Statistical analysis

We summarized the baseline characteristics using descriptive statistics. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations between three plant-based diet indices and the risk of EC. The follow-up time in person-years was calculated from the baseline to the date of diagnosis of EC, the date of death, or the end of the follow-up period (31 December 2022), whichever came first. We categorized PDI, hPDI, and uPDI into quartiles (quartile 1 to quartile 4). In the basic model, PDI, hPDI, and uPDI were included separately. In the minimally adjusted model, we adjusted for age and gender. In the fully adjusted model, we further adjusted for marital status, educational status, number of family members, annual income, smoking status, prior history of digestive diseases, family history of cancer, and BMI categories (<23.9 kg/m2, ≥24.0 kg/m2) (25). We also estimated the risk of EC per 10-point increase in PDI, hPDI, and uPDI. We separately plotted three knots of cubic splines to explore nonlinearity between three plant-based diet indices and the risk of EC. The Wald test was used to assess whether the observed relationships were linear or nonlinear. We conducted correlation analysis to assess the relationships among various food groups. Additionally, we performed food component analysis to investigate the individual contributions of healthy plant food, less healthy plant food, and animal food groups.

We performed several sensitivity analyses to test the robustness of the results; these included the exclusion of individuals who developed EC within one year of follow-up. Additionally, we excluded individuals with diabetes, stroke, or myocardial infarction to account for the possibility that their usual diet may have changed following the diagnosis of these chronic diseases. Moreover, we explored the associations of PDI, hPDI, and uPDI with ESCC incidence. Given that alcohol was not originally included in the PDIs, we also included alcohol consumption as a covariate in our analysis rather than in the PDIs.

All the statistical analyses were carried out using R software (Version 4.1.1; R Foundation for Statistical Computing, Vienna, Austria). P<0.05 was considered to indicate statistical significance in two-sided tests.

Results

Baseline characteristics of participants

Supplementary Table S3 provides an overview of the baseline characteristics of the 15,184 participants included in the study, spanning from 2005 to 2009. The participants had a mean age of 51.84 years [standard deviation (SD): 7.50], and 54.01% were females. The majority (93.45%) were married, and 49.51% had completed nine years of compulsory education. Approximately 27.73% of the participants were current smokers, and 40.15% were obese. Approximately 11.75% had a history of digestive diseases, and 29.50% had a family history of cancer.

Table S3. Participants’ characteristics at baseline.

Variables n (%) χ2 P
Healthy population (N=15,008) EC case (N=176) Total (N=15,184)
EC, esophageal cancer; BMI, body mass index.
Gender
 Male 6,865 (45.74) 118 (67.05) 6,983 (45.99) 31.784 <0.001
 Female 8,143 (54.26) 58 (32.95) 8,201 (54.01)
Age at baseline (year)
 40−49 6,255 (41.68) 36 (20.45) 6,291 (41.43) 32.988 <0.001
 50−59 6,132 (40.86) 102 (57.95) 6,234 (41.06)
 60−69 2,621 (17.46) 38 (21.59) 2,659 (17.51)
Marital status
 Married 14,029 (93.48) 160 (90.91) 14,189 (93.45) 1.873 0.171
 Unmarried/divorced/widowed 979 (6.52) 16 (9.09) 995 (6.55)
Educational status
 No education 2,201 (14.67) 20 (11.36) 2,221 (14.63) 2.085 0.353
 Elementary school 5,384 (35.87) 61 (34.66) 5,445 (35.86)
 Middle school and above 7,423 (49.46) 95 (53.98) 7,518 (49.51)
No. of family members
 1−2 3,281 (21.86) 58 (32.95) 3,339 (21.99) 15.412 0.004
 3 2,856 (19.03) 22 (12.50) 2,878 (18.95)
 4 5,038 (33.57) 51 (28.98) 5,089 (33.52)
 5 2,502 (16.67) 32 (18.18) 2,534 (16.69)
 ≥6 1,331 (8.87) 13 (7.39) 1,344 (8.85)
Annual income (CNY/person)
 ≤5,000 4,857 (32.36) 69 (39.20) 4,926 (32.44) 3.715 0.054
 >5,000 10,151 (67.64) 107 (60.80) 10,258 (67.56)
BMI (kg/m2)
 <18.5 515 (3.43) 8 (4.55) 525 (3.46) 6.150 0.407
 18.5−23.9 8,453 (56.32) 110 (62.50) 8,562 (56.39)
 24.0−27.9 4,805 (32.02) 51 (28.98) 4,855 (31.97)
 ≥28.0 1,235 (8.23) 7 (3.98) 1,242 (8.18)
Smoking status
 No 10,868 (72.41) 105 (59.66) 10,973 (72.27) 14.123 <0.001
 Yes 4,140 (27.59) 71 (40.34) 4,211 (27.73)
History of digestive diseases
 No 13,246 (88.26) 154 (87.50) 13,400 (88.25) 0.097 0.756
 Yes 1,762 (11.74) 22 (12.50) 1,784 (11.75)
Family history of cancer
 No 10,587 (70.54) 118 (67.05) 10,705 (70.50) 1.023 0.312
 Yes 4,421 (29.46) 58 (32.95) 4,479 (29.50)

The baseline characteristics of 15,184 participants across the PDIs are displayed in Table 1. Compared with participants in the lowest quartile of the PDI and hPDI, those in the highest quartile were more likely to be female, be married, have a higher BMI, and have a higher income (Table 1, Supplementary Tables S4, S5). They were also more likely to be nonsmokers and not have a family history of cancer. Conversely, in the case of uPDI, participants in the highest quartile were more likely to be male and unmarried and to have a lower BMI and a lower income than were those in the lowest quartile (Table 1, Supplementary Table S6).

Table 1. Baseline characteristics of participants by lowest vs. highest quartile of three plant-based diet indices in the cohort.

Variables hPDI [n (%)] uPDI [n (%)] PDI [n (%)]
Quartile 1 Quartile 4 Quartile 1 Quartile 4 Quartile 1 Quartile 4
PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index.
Gender
 Male 2,410 (53.72) 1,452 (38.55) 1,673 (40.49) 1,645 (53.05) 1,898 (50.00) 1,216 (42.03)
 Female 2,076 (46.28) 2,315 (61.45) 2,459 (59.51) 1,456 (46.95) 1,898 (50.00) 1,677 (57.97)
Age at baseline (year)
 40−49 1,823 (40.64) 1,615 (42.87) 1,798 (43.51) 1,261 (40.66) 1,488 (39.20) 1,281 (44.28)
 50−59 1,851 (41.26) 1,522 (40.40) 1,660 (40.17) 1,271 (40.99) 1,626 (42.83) 1,141 (39.44)
 60−69 812 (18.10) 630 (16.72) 674 (16.31) 569 (18.35) 682 (17.97) 471 (16.28)
Marital status
 Married 4,153 (92.58) 3,535 (93.84) 3,899 (94.36) 2,850 (91.91) 3,501 (92.23) 2,737 (94.61)
 Unmarried/divorced/widowed 333 (7.42) 232 (6.16) 233 (5.64) 251 (8.09) 295 (7.77) 156 (5.39)
Educational status
 No education 596 (13.29) 675 (17.92) 747 (18.08) 392 (12.64) 446 (11.75) 570 (19.70)
 Elementary school 1,551 (34.57) 1,400 (37.16) 1,484 (35.91) 1,113 (35.89) 1,439 (37.91) 937 (32.39)
 Middle school and above 2,339 (52.14) 1,692 (44.92) 1,901 (46.01) 1,596 (51.47) 1,911 (50.34) 1,386 (47.91)
No. of family members
 1−2 1,033 (23.03) 765 (20.31) 832 (20.14) 701 (22.61) 885 (23.31) 574 (19.84)
 3 821 (18.30) 750 (19.91) 832 (20.14) 531 (17.12) 698 (18.39) 584 (20.19)
 4 1,456 (32.46) 1,269 (33.69) 1,395 (33.76) 1,051 (33.89) 1,253 (33.01) 993 (34.32)
 5 749 (16.70) 671 (17.81) 717 (17.35) 520 (16.77) 638 (16.81) 486 (16.80)
 ≥6 427 (9.52) 312 (8.28) 356 (8.62) 298 (9.61) 322 (8.48) 256 (8.85)
Annual income (CNY/person)
 ≤5,000 1,538 (34.28) 1,091 (28.96) 1,133 (27.42) 1,114 (35.92) 1,366 (35.99) 848 (29.31)
 >5,000 2,948 (65.72) 2,676 (71.04) 2,999 (72.58) 1,987 (64.08) 2,430 (64.01) 2,045 (70.69)
BMI (kg/m2)
 <18.5 149 (3.32) 125 (3.32) 144 (3.48) 108 (3.48) 161 (4.24) 112 (3.87)
 18.5−23.9 2,649 (59.05) 2,022 (53.68) 2,234 (54.07) 1,797 (57.95) 2,136 (56.27) 1,616 (55.86)
 24.0−27.9 1,355 (30.21) 1,266 (33.61) 1,372 (33.20) 956 (30.83) 1,197 (31.53) 941 (32.53)
 ≥28.0 333 (7.42) 354 (9.40) 382 (9.24) 240 (7.74) 302 (7.96) 224 (7.74)
Smoking status
 No 2,793 (62.26) 3,075 (81.63) 3,343 (80.91) 1,932 (62.30) 2,556 (67.33) 2,298 (79.43)
 Yes 1,693 (37.74) 692 (18.37) 789 (19.09) 1,169 (37.70) 1,240 (32.67) 595 (20.57)
History of digestive diseases
 No 3,854 (85.91) 3,347 (88.85) 3,633 (87.92) 2,679 (86.39) 3,313 (87.28) 2,514 (86.90)
 Yes 632 (14.09) 420 (11.15) 499 (12.08) 422 (13.61) 483 (12.72) 379 (13.10)
Family history of cancer
 No 3,104 (69.19) 2,622 (69.60) 2,867 (69.39) 2,179 (70.27) 2,700 (71.13) 2,084 (72.04)
 Yes 1,382 (30.81) 1,145 (30.40) 1,265 (30.61) 922 (29.73) 1,096 (28.87) 809 (27.96)

Table S4. Demographics for participants according to PDI.

Variables n (%) χ2 P
Quartile 1 Quartile 2 Quartile 3 Quartile 4
PDI, overall plant-based diet index; BMI, body mass index.
Gender
 Male 1,898 (50.00) 1,966 (45.50) 1,903 (45.59) 1,216 (42.03) 43.502 <0.001
 Female 1,898 (50.00) 2,355 (54.50) 2,271 (54.41) 1,677 (57.97)
Age at baseline (year)
 40−49 1,488 (39.20) 1,764 (40.82) 1,758 (42.12) 1,281 (44.28) 23.043 <0.001
 50−59 1,626 (42.83) 1,812 (41.93) 1,655 (39.65) 1,141 (39.44)
 60−69 682 (17.97) 745 (17.24) 761 (18.23) 471 (16.28)
Marital status
 Married 3,501 (92.23) 4,052 (93.77) 3,899 (93.41) 2,737 (94.61) 16.332 <0.001
 Unmarried/divorced/widowed 295 (7.77) 269 (6.23) 275 (6.59) 156 (5.39)
Educational status
 No education 446 (11.75) 581 (13.45) 624 (14.95) 570 (19.70) 94.141 <0.001
 Elementary school 1,439 (37.91) 1,563 (36.17) 1,506 (36.08) 937 (32.39)
 Middle school and above 1,911 (50.34) 2,177 (50.38) 2,044 (48.97) 1,386 (47.91)
No. of family members
 1−2 885 (23.31) 955 (22.10) 925 (22.16) 574 (19.84) 15.592 0.211
 3 698 (18.39) 803 (18.58) 793 (19.00) 584 (20.19)
 4 1,253 (33.01) 1,471 (34.04) 1,372 (32.87) 993 (34.32)
 5 638 (16.81) 705 (16.32) 705 (16.89) 486 (16.80)
 ≥6 322 (8.48) 387 (8.96) 379 (9.08) 256 (8.85)
Annual income (CNY/person)
 ≤5,000 1,366 (35.99) 1,376 (31.84) 1,336 (32.01) 848 (29.31) 35.738 <0.001
 >5,000 2,430 (64.01) 2,945 (68.16) 2,838 (67.99) 2,045 (70.69)
BMI (kg/m2)
 <18.5 161 (4.24) 134 (3.10) 116 (2.78) 112 (3.87) 17.982 0.035
 18.5−23.9 2,136 (56.27) 2,452 (56.75) 2,359 (56.52) 1,616 (55.86)
 24.0−27.9 1,197 (31.53) 1,369 (31.68) 1,349 (32.32) 941 (32.53)
 ≥28.0 302 (7.96) 366 (8.47) 350 (8.39) 224 (7.74)
Smoking status
 No 2,556 (67.33) 3,037 (70.28) 3,082 (73.84) 2,298 (79.43) 133.830 <0.001
 Yes 1,240 (32.67) 1,284 (29.72) 1,092 (26.16) 595 (20.57)
History of digestive diseases
 No 3,313 (87.28) 3,851 (89.12) 3,722 (89.17) 2,514 (86.90) 15.152 0.002
 Yes 483 (12.72) 470 (10.88) 452 (10.83) 379 (13.10)
Family history of cancer
 No 2,700 (71.13) 2,973 (68.80) 2,948 (70.63) 2,084 (72.04) 10.013 0.018
 Yes 1,096 (28.87) 1,348 (31.20) 1,226 (29.37) 809 (27.96)

Table S5. Demographics for participants according to hPDI.

Variables n (%) χ2 P
Quartile 1 Quartile 2 Quartile 3 Quartile 4
hPDI, healthful plant-based diet index; BMI, body mass index.
Gender 211.685 <0.001
 Male 2,410 (53.72) 1,735 (47.37) 1,386 (42.41) 1,452 (38.55)
 Female 2,076 (46.28) 1,928 (52.63) 1,882 (57.59) 2,315 (61.45)
Age at baseline (year)
 40−49 1,823 (40.64) 1,523 (41.58) 1,330 (40.70) 1,615 (42.87) 9.273 0.159
 50−59 1,851 (41.26) 1,475 (40.27) 1,386 (42.41) 1,522 (40.40)
 60−69 812 (18.10) 665 (18.15) 552 (16.89) 630 (16.72)
Marital status
 Married 4,153 (92.58) 3,409 (93.07) 3,092 (94.61) 3,535 (93.84) 14.645 0.002
 Unmarried/divorced/widowed 333 (7.42) 254 (6.93) 176 (5.39) 232 (6.16)
Educational status
 No education 596 (13.29) 482 (13.16) 468 (14.32) 675 (17.92) 67.578 <0.001
 Elementary school 1,551 (34.57) 1,306 (35.65) 1,188 (36.35) 1,400 (37.16)
 Middle school and above 2,339 (52.14) 1,875 (51.19) 1,612 (49.33) 1,692 (44.92)
No. of family members
 1−2 1,033 (23.03) 848 (23.15) 693 (21.21) 765 (20.31) 26.469 0.009
 3 821 (18.30) 690 (18.84) 617 (18.88) 750 (19.91)
 4 1,456 (32.46) 1,234 (33.69) 1,130 (34.58) 1,269 (33.69)
 5 749 (16.70) 591 (16.13) 523 (16.00) 671 (17.81)
 ≥6 427 (9.52) 300 (8.19) 305 (9.33) 312 (8.28)
Annual income (CNY/person)
 ≤5,000 1,538 (34.28) 1,264 (34.51) 1,033 (31.61) 1,091 (28.96) 35.924 <0.001
 >5,000 2,948 (65.72) 2,399 (65.49) 2,235 (68.39) 2,676 (71.04)
BMI (kg/m2)
 <18.5 149 (3.32) 125 (3.41) 124 (3.79) 125 (3.32) 31.863 <0.001
 18.5−23.9 2,649 (59.05) 2,085 (56.92) 1,807 (55.29) 2,022 (53.68)
 24.0−27.9 1,355 (30.21) 1,170 (31.94) 1,065 (32.59) 1,266 (33.61)
 ≥28.0 333 (7.42) 283 (7.73) 272 (8.32) 354 (9.40)
Smoking status
 No 2,793 (62.26) 2,622 (71.58) 2,483 (75.98) 3,075 (81.63) 412.231 <0.001
 Yes 1,693 (37.74) 1,041 (28.42) 785 (24.02) 692 (18.37)
History of digestive diseases
 No 3,854 (85.91) 3,279 (89.52) 2,920 (89.35) 3,347 (88.85) 34.457 <0.001
 Yes 632 (14.09) 384 (10.48) 348 (10.65) 420 (11.15)
Family history of cancer
 No 3,104 (69.19) 2,647 (72.26) 2,332 (71.36) 2,622 (69.60) 11.771 0.008
 Yes 1,382 (30.81) 1,016 (27.74) 936 (28.64) 1,145 (30.40)

Table S6. Demographics for participants according to uPDI.

Variables n (%) χ2 P
Quartile 1 Quartile 2 Quartile 3 Quartile 4
uPDI, unhealthful plant-based diet index; BMI, body mass index.
Gender
 Male 1,673 (40.49) 2,193 (45.19) 1,472 (47.51) 1,645 (53.05) 116.676 <0.001
 Female 2,459 (59.51) 2,660 (54.81) 1,626 (52.49) 1,456 (46.95)
Age at baseline (year)
 40−49 1,798 (43.51) 1,988 (40.96) 1,244 (40.15) 1,261 (40.66) 12.758 0.047
 50−59 1,660 (40.17) 2,003 (41.27) 1,300 (41.96) 1,271 (40.99)
 60−69 674 (16.31) 862 (17.76) 554 (17.88) 569 (18.35)
Marital status
 Married 3,899 (94.36) 4,567 (94.11) 2,873 (92.74) 2,850 (91.91) 23.664 <0.001
 Unmarried/divorced/widowed 233 (5.64) 286 (5.89) 225 (7.26) 251 (8.09)
Educational status
 No education 747 (18.08) 689 (14.20) 393 (12.69) 392 (12.64) 66.462 <0.001
 Elementary school 1,484 (35.91) 1,745 (35.96) 1,103 (35.60) 1,113 (35.89)
 Middle school and above 1,901 (46.01) 2,419 (49.85) 1,602 (51.71) 1,596 (51.47)
No. of family members
 1−2 832 (20.14) 1,064 (21.92) 742 (23.95) 701 (22.61) 27.804 0.006
 3 832 (20.14) 931 (19.18) 584 (18.85) 531 (17.12)
 4 1,395 (33.76) 1,647 (33.94) 996 (32.15) 1,051 (33.89)
 5 717 (17.35) 795 (16.38) 502 (16.20) 520 (16.77)
 ≥6 356 (8.62) 416 (8.57) 274 (8.84) 298 (9.61)
Annual income (CNY/person)
 ≤5,000 1,133 (27.42) 1,569 (32.33) 1,110 (35.83) 1,114 (35.92) 80.947 <0.001
 >5,000 2,999 (72.58) 3,284 (67.67) 1,988 (64.17) 1,987 (64.08)
BMI (kg/m2)
 <18.5 144 (3.48) 154 (3.17) 117 (3.78) 108 (3.48) 20.280 0.016
 18.5−23.9 2,234 (54.07) 2,753 (56.73) 1,779 (57.42) 1,797 (57.95)
 24.0−27.9 1,372 (33.20) 1,557 (32.08) 971 (31.34) 956 (30.83)
 ≥28.0 382 (9.24) 389 (8.02) 231 (7.46) 240 (7.74)
Smoking status
 No 3,343 (80.91) 3,519 (72.51) 2,179 (70.34) 1,932 (62.30) 313.378 <0.001
 Yes 789 (19.09) 1,334 (27.49) 919 (29.66) 1,169 (37.70)
History of digestive diseases
 No 3,633 (87.92) 4,330 (89.22) 2,758 (89.03) 2,679 (86.39) 16.983 <0.001
 Yes 499 (12.08) 523 (10.78) 340 (10.97) 422 (13.61)
Family history of cancer
 No 2,867 (69.39) 3,467 (71.44) 2,192 (70.76) 2,179 (70.27) 4.710 0.194
 Yes 1,265 (30.61) 1,386 (28.56) 906 (29.24) 922 (29.73)

PDIs and risk of EC

During 219,365 person-years of follow-up, a total of 176 patients with EC were identified within the cohort. According to the fully adjusted model (Table 2), the PDI was modestly inversely associated with EC incidence, but the difference was not statistically significant (HR comparing extreme quartiles: 0.80, 95% CI: 0.50−1.30; HR per 10-unit increase: 0.84, 95% CI: 0.57−1.22; Ptrend=0.358). When we analyzed hPDI and uPDI separately, we found a stronger inverse association between hPDI and EC incidence (HR comparing extreme quartiles: 0.50, 95% CI: 0.32−0.77; HR per 10-unit increase: 0.42, 95% CI: 0.27−0.66; Ptrend<0.001) and a positive association for uPDI (HR comparing extreme quartiles: 1.80, 95% CI: 1.16−2.82; HR per 10-unit increase: 1.90, 95% CI: 1.26−2.88; Ptrend=0.002). No evidence of nonlinearity was found for hPDI or uPDI (Figure 2).

Table 2. Association between three plant-based diet indices and risks of EC.

Varialbles Sample (cases) Not adjusted model Minimally adjusted model Fully adjusted model
HR (95% CI) P HR (95% CI) P HR (95% CI) P
EC, esophageal cancer; PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index; HR, hazard ratio; 95% CI, 95% confidence interval. Not adjusted model, PDI, hPDI, and uPDI are included separately; Minimally adjusted model, adjusted age and gender; Fully adjusted model, adjusted for age, gender, marital status, educational status, number of family members, annual income, smoking status, history of digestive diseases, family history of cancer, and BMI categories.
PDI by quartiles
 Quartile 1 3,796 (50) Ref Ref Ref
 Quartile 2 4,321 (51) 0.91 (0.61−1.34) 0.620 0.95 (0.64−1.41) 0.807 0.96 (0.65−1.42) 0.826
 Quartile 3 4,174 (49) 0.90 (0.61−1.34) 0.602 0.96 (0.64−1.42) 0.819 0.97 (0.66−1.45) 0.892
 Quartile 4 2,893 (26) 0.69 (0.43−1.11) 0.131 0.77 (0.48−1.24) 0.286 0.80 (0.50−1.30) 0.371
Per 10 score increase 15,184 (176) 0.77 (0.55−1.08) 0.123 0.80 (0.57−1.13) 0.206 0.84 (0.57−1.22) 0.358
hPDI by quartiles
 Quartile 1 4,486 (78) Ref Ref Ref
 Quartile 2 3,663 (40) 0.63 (0.43−0.92) 0.016 0.67 (0.46−0.98) 0.038 0.67 (0.46−0.99) 0.042
 Quartile 3 3,268 (31) 0.54 (0.36−0.83) 0.004 0.60 (0.39−0.91) 0.015 0.61 (0.40−0.92) 0.020
 Quartile 4 3,767 (27) 0.41 (0.27−0.64) <0.001 0.48 (0.31−0.74) 0.001 0.50 (0.32−0.77) 0.002
Per 10 score increase 15,184 (176) 0.38 (0.23−0.54) <0.001 0.41 (0.26−0.63) <0.001 0.42 (0.27−0.66) <0.001
uPDI by quartiles
 Quartile 1 4,132 (32) Ref Ref Ref
 Quartile 2 4,853 (46) 1.21 (0.77−1.91) 0.398 1.15 (0.73−1.80) 0.551 1.12 (0.71−1.76) 0.625
 Quartile 3 3,098 (46) 1.90 (1.21−2.99) 0.005 1.74 (1.10−2.73) 0.017 1.67 (1.06−2.62) 0.028
 Quartile 4 3,101 (52) 2.13 (1.37−3.31) <0.001 1.87 (1.20−2.92) 0.005 1.80 (1.16−2.82) 0.009
Per 10 score increase 15,184 (176) 1.24 (1.50−3.35) <0.001 1.97 (1.31−2.95) 0.001 1.90 (1.26−2.88) 0.002

Figure 2.

Figure 2

Cubic splines for three plant-based diet indices and risks of EC. (A) Cubic splines for PDI (Poverall=0.218, Pnonlinear=0.382); (B) Cubic splines for hPDI (Poverall<0.001, Pnonlinear=0.539); (C) Cubic splines for uPDI (Poverall<0.001, Pnonlinear=0.712). EC, esophageal cancer; PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index.

Subgroup analyses

Associations of PDI, hPDI, and uPDI with the risk of EC remained consistent across the subgroups (Supplementary Table S7). The results indicated that the directions of these associations were not significantly different among subgroups stratified by age at baseline, gender, marital status, educational status, number of family members, annual income, smoking status, BMI, history of digestive diseases or family history of cancer (all Pinteraction>0.05).

Table S7. Subgroup analyses for three plant-based diet indices and risks of EC.

Variables PDI uPDI hPDI
HR (95% CI)* P Pinteraction HR (95% CI)* P Pinteraction HR (95% CI)* P Pinteraction
PDI, overall plant-based diet index; EC, esophageal cancer; uPDI, unhealthful plant-based diet index; hPDI, healthful plant-based diet index; HR, hazard ratio; 95% CI, 95% confidence interval; *, HR for quartiles of PDI, hPDI, and uPDI. The HR and 95% CI of Quartiles 2, 3, 4 were calculated with reference to Quartile 1.
Gender
 Male 1.00 1.00 1.00
  0.86 (0.54−1.38) 0.528 1.21 (0.70−2.09) 0.499 0.72 (0.46−1.15) 0.170
  0.91 (0.57−1.46) 0.703 1.25 (0.70−2.24) 0.452 0.63 (0.38−1.07) 0.089
  0.66 (0.36−1.20) 0.173 1.71 (0.99−2.93) 0.053 0.56 (0.32−0.97) 0.040
 Female 1.00 0.848 1.00 0.123 1.00 0.935
  1.19 (0.58−2.45) 0.626 0.93 (0.41−2.12) 0.863 0.57 (0.29−1.12) 0.103
  1.14 (0.54−2.38) 0.730 2.63 (1.26−5.48) 0.010 0.54 (0.27−1.08) 0.082
  1.15 (0.51−2.58) 0.736 2.09 (0.94−4.64) 0.070 0.39 (0.18−0.81) 0.012
Age at baseline (year)
 40−49 1.00 1.00
  0.82 (0.35−1.94) 0.658 0.96 (0.45−2.05) 0.926
  0.59 (0.23−1.54) 0.284 0.60 (0.23−1.54) 0.289
  1.00 (0.39−2.53) 0.999 0.18 (0.04−0.79) 0.023
 50−59 1.00 0.397 1.00 1.00 0.188
  1.01 (0.59−1.73) 0.966 1.01 (0.54−1.87) 0.981 0.63 (0.38−1.04) 0.073
  1.33 (0.80−2.22) 0.278 1.76 (0.96−3.20) 0.067 0.57 (0.33−0.98) 0.044
  0.84 (0.44−1.63) 0.614 2.11 (1.19−3.77) 0.011 0.45 (0.25−0.81) 0.007
 60−69 1.00 1.00 1.00
  0.99 (0.46−2.15) 0.980 0.49 (0.20−1.20) 0.116 0.52 (0.20−1.35) 0.181
  0.60 (0.25−1.45) 0.253 1.00 (0.44−2.28) 0.994 0.74 (0.30−1.83) 0.519
  0.50 (0.16−1.56) 0.234 0.58 (0.22−1.48) 0.254 1.04 (0.46−2.34) 0.930
Marital status
 Married 1.00 1.00 1.00
  1.04 (0.69−1.58) 0.836 1.22 (0.76−1.97) 0.415 0.69 (0.46−1.04) 0.073
  1.01 (0.66−1.54) 0.964 1.85 (1.15−2.99) 0.012 0.62 (0.40−0.95) 0.030
 Unmarried/divorced/
widowed
0.90 (0.55−1.47) 0.673 1.94 (1.21−3.12) 0.006 0.48 (0.30−0.76) 0.002
 
 
 
Educational status
 Elementary school
and below
1.00 1.00 1.00
  0.90 (0.50−1.62) 0.721 1.09 (0.59−1.99) 0.784 0.60 (0.32−1.10) 0.098
  1.00 (0.56−1.78) 0.994 1.48 (0.80−2.75) 0.215 0.77 (0.43−1.39) 0.386
  0.77 (0.38−1.56) 0.473 0.98 (0.50−1.92) 0.952 0.62 (0.34−1.13) 0.118
 Middle school and above 1.00 0.965 1.00 0.093 1.00 0.435
  0.98 (0.58−1.66) 0.935 1.22 (0.62−2.43) 0.564 0.74 (0.45−1.20) 0.221
  0.91 (0.53−1.58) 0.743 1.97 (1.00−3.89) 0.049 0.49 (0.27−0.89) 0.020
  0.80 (0.42−1.54) 0.509 2.95 (1.56−5.60) 0.001 0.40 (0.21−0.78) 0.007
No. of family members
 1−3 1.00 1.00 1.00
  1.06 (0.60−1.90) 0.835 0.94 (0.51−1.75) 0.853 0.77 (0.43−1.39) 0.389
  1.06 (0.58−1.92) 0.854 1.24 (0.66−2.33) 0.507 0.81 (0.44−1.48) 0.489
  0.91 (0.45−1.84) 0.785 1.09 (0.56−2.11) 0.793 0.82 (0.44−1.51) 0.519
 4−6 1.00 0.970 1.00 0.263 1.00 0.197
  0.88 (0.52−1.50) 0.639 1.36 (0.70−2.65) 0.365 0.63 (0.38−1.04) 0.071
  0.92 (0.54−1.57) 0.773 2.32 (1.20−4.49) 0.012 0.48 (0.27−0.85) 0.013
  0.72 (0.37−1.37) 0.317 2.73 (1.45−5.14) 0.002 0.31 (0.16−0.60) 0.001
Annual income (CNY/person)
 ≤5,000 1.00 1.00 1.00
  1.06 (0.58−1.94) 0.859 0.77 (0.38−1.54) 0.462 0.59 (0.31−1.11) 0.101
  0.99 (0.53−1.85) 0.985 0.86 (0.41−1.78) 0.676 0.62 (0.32−1.22) 0.168
  0.75 (0.33−1.70) 0.490 1.29 (0.67−2.49) 0.452 0.63 (0.32−1.23) 0.176
 >5,000 1.00 0.912 1.00 0.189 1.00 0.746
  0.87 (0.52−1.45) 0.587 1.44 (0.79−2.62) 0.239 0.73 (0.45−1.18) 0.203
  0.92 (0.55−1.54) 0.762 2.50 (1.38−4.53) 0.002 0.61 (0.36−1.05) 0.075
  0.80 (0.44−1.45) 0.460 2.18 (1.19−3.99) 0.012 0.43 (0.24−0.78) 0.005
BMI (kg/m2)
 <23.9 1.00 1.00 1.00
  0.97 (0.61−1.56) 0.906 1.19 (0.70−2.01) 0.526 0.77 (0.48−1.24) 0.275
  0.89 (0.54−1.45) 0.631 1.30 (0.74−2.28) 0.357 0.84 (0.52−1.38) 0.499
  0.85 (0.48−1.50) 0.581 1.49 (0.86−2.56) 0.153 0.63 (0.37−1.08) 0.090
 ≥24 1.00 0.808 1.00 0.082 1.00 0.098
  0.90 (0.45−1.81) 0.770 0.89 (0.36−2.19) 0.793 0.54 (0.28−1.03) 0.063
  1.15 (0.59−2.25) 0.673 2.61 (1.17−5.80) 0.019 0.27 (0.11−0.65) 0.004
  0.70 (0.28−1.70) 0.426 2.58 (1.16−5.72) 0.020 0.33 (0.15−0.72) 0.005
Smoking status
 Yes 1.00 1.00 1.00
  0.86 (0.48−1.52) 0.597 1.52 (0.70−3.31) 0.289 0.86 (0.49−1.50) 0.596
  0.66 (0.35−1.26) 0.208 1.42 (0.62−3.25) 0.408 0.53 (0.26−1.10) 0.090
  0.74 (0.34−1.58) 0.433 1.91 (0.89−4.11) 0.098 0.33 (0.13−0.83) 0.019
 No 1.00 0.562 1.00 0.323 1.00 0.354
  1.06 (0.62−1.81) 0.831 0.90 (0.51−1.60) 0.718 0.57 (0.33−0.96) 0.035
  1.23 (0.73−2.07) 0.428 1.84 (1.07−3.16) 0.028 0.64 (0.38−1.08) 0.094
  0.89 (0.48−1.65) 0.704 1.76 (1.01−3.09) 0.047 0.57 (0.34−0.96) 0.034
History of digestive diseases
 Yes 1.00 1.00 1.00
  0.70 (0.25−1.99) 0.506 0.46 (0.11−1.87) 0.277 0.17 (0.02−1.34) 0.093
  0.63 (0.21−1.89) 0.407 0.60 (0.15−2.49) 0.486 0.95 (0.33−2.75) 0.925
  0.32 (0.07−1.52) 0.152 1.54 (0.53−4.51) 0.427 0.67 (0.21−2.13) 0.493
 No 1.00 0.578 1.00 0.207 1.00 0.194
  1.01 (0.66−1.54) 0.962 1.26 (0.77−2.05) 0.355 0.73 (0.49−1.09) 0.125
  1.05 (0.68−1.60) 0.839 1.88 (1.15−3.07) 0.012 0.58 (0.36−0.91) 0.018
  0.92 (0.55−1.52) 0.740 1.82 (1.11−2.98) 0.018 0.48 (0.30−0.77) 0.003
Family history of cancer
 Yes 1.00 1.00 1.00
  1.16 (0.55−2.45) 0.700 0.99 (0.43−2.31) 0.989 0.59 (0.29−1.18) 0.137
  1.41 (0.68−2.92) 0.362 1.90 (0.86−4.22) 0.114 0.66 (0.33−1.33) 0.245
  1.52 (0.68−3.40) 0.310 2.16 (1.00−4.67) 0.049 0.44 (0.20−0.97) 0.042
 No 1.00 0.214 1.00 0.690 1.00 0.916
  0.90 (0.57−1.42) 0.649 1.17 (0.69−2.01) 0.558 0.73 (0.46−1.16) 0.180
  0.82 (0.51−1.32) 0.421 1.56 (0.90−2.72) 0.114 0.60 (0.35−1.00) 0.052
  0.57 (0.31−1.05) 0.071 1.61 (0.93−2.80) 0.087 0.53 (0.31−0.91) 0.022

Sensitivity analyses

According to the sensitivity analyses, when we excluded individuals who developed EC within one year of follow-up, the results were the same as those of the main analysis, and we found an inverse association between hPDI and EC (HR comparing extreme quartiles: 0.50, 95% CI: 0.32−0.79) and a positive association between uPDI and EC (HR comparing extreme quartiles: 1.73, 95% CI: 1.09−2.75) (Supplementary Table S8). We further excluded individuals who had diabetes, stroke, or myocardial infarction, and the results also remained robust (Supplementary Table S9). This inverse association was also observed for hDPI (HR comparing extreme quartiles: 0.50, 95% CI: 0.32−0.77). Conversely, uPDI was positively associated with EC (HR comparing extreme quartiles: 1.81, 95% CI: 1.16−2.82). We also excluded individuals who were diagnosed with esophageal adenocarcinoma (EAC) or other histological subtypes (Supplementary Table S10). We observed an inverse association for hDPI (HR comparing extreme quartiles: 0.50, 95% CI: 0.32−0.79) and a positive association for uPDI with ESCC (HR comparing extreme quartiles: 1.79, 95% CI: 1.14−2.82). To account for the effect of alcoholic beverages, alcoholic beverages were excluded from the PDIs, and the results were robust (Supplementary Table S11). hPDI was inversely associated with EC incidence (HR comparing extreme quartiles: 0.55, 95% CI: 0.37−0.82). uPDI was positively associated with EC incidence (HR comparing extreme quartiles: 1.65, 95% CI: 1.07−2.54).

Table S8. Sensitivity analysisa of association between three plant-based diet indices and risks of EC.

Variables Sample (cases) Not adjusted model Minimally adjusted model Fully adjusted model
HR (95% CI) P HR (95% CI) P HR (95% CI) P
a, Excluded individuals who developed EC within one year of follow-up; EC, esophageal cancer; Not adjusted model, PDI, hPDI, and uPDI are included separately; Minimally adjusted model, adjusted age and gender; Fully adjusted model, adjusted for age, gender, marital status, educational status, number of family members, annual income, smoking status, history of digestive diseases, and family history of cancer, and BMI categories. PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index; HR, hazard ratio; 95% CI, 95% confidence interval.
PDI by quartiles
 Quartile 1 3,790 (44) Ref Ref Ref
 Quartile 2 4,320 (50) 1.01 (0.67−1.52) 0.961 1.06 (0.71−1.59) 0.771 1.06 (0.71−1.60) 0.765
 Quartile 3 4,172 (47) 0.98 (0.65−1.48) 0.932 1.04 (0.69−1.57) 0.847 1.06 (0.70−1.61) 0.773
 Quartile 4 2,892 (25) 0.76 (0.46−1.24) 0.271 0.84 (0.52−1.38) 0.502 0.89 (0.54−1.45) 0.635
Per 10 score increase 15,174 (166) 0.77 (0.53−1.13) 0.184 0.84 (0.57−1.24) 0.377 0.88 (0.59−1.30) 0.520
hPDI by quartiles
 Quartile 1 4,480 (72) Ref Ref Ref
 Quartile 2 3,662 (39) 0.66 (0.45−0.98) 0.038 0.70 (0.48−1.04) 0.078 0.71 (0.48−1.05) 0.087
 Quartile 3 3,267 (30) 0.57 (0.37−0.87) 0.010 0.62 (0.41−0.96) 0.030 0.64 (0.41−0.98) 0.040
 Quartile 4 3,765 (25) 0.42 (0.26−0.65) 0.000 0.48 (0.30−0.76) 0.002 0.50 (0.32−0.79) 0.003
Per 10 score increase 15,174 (166) 0.37 (0.24−0.58) <0.001 0.44 (0.28−0.68) <0.001 0.45 (0.29−0.72) 0.001
uPDI by quartiles
 Quartile 1 4,130 (30) Ref Ref Ref
 Quartile 2 4,851 (44) 1.24 (0.78−1.97) 0.366 1.17 (0.74−1.86) 0.508 1.13 (0.71−1.80) 0.603
 Quartile 3 3,097 (45) 1.98 (1.25−3.15) 0.004 1.81 (1.14−2.88) 0.012 1.72 (1.08−2.75) 0.022
 Quartile 4 3,196 (47) 2.05 (1.30−3.24) 0.002 1.81 (1.14−2.86) 0.012 1.73 (1.09−2.75) 0.021
Per 10 score increase 15,174 (166) 2.20 (1.44−3.32) <0.001 1.93 (1.27−2.93) 0.002 1.85 (1.21−2.84) 0.005

Table S9. Sensitivity analysisb of association between three plant-based diet indices and risks of EC.

Variables Sample (cases) Not adjusted model Minimally adjusted model Fully adjusted model
HR (95% CI) P HR (95% CI) P HR (95% CI) P
b, Excluded individuals who had diabetes, stroke, or myocardial infarction, to account for the possibility that their usual diet changed due to the diagnosis of these chronic diseases; EC, esophageal cancer; Not adjusted model, PDI, hPDI, and uPDI are included separately; Minimally adjusted model, adjusted age and gender; Fully adjusted model, adjusted for age, gender, marital status, educational status, number of family members, annual income, smoking status, history of digestive diseases, and family history of cancer, and BMI categories; PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index; HR, hazard ratio; 95% CI, 95% confidence interval.
PDI by quartiles
 Quartile 1 3,757 (50) Ref Ref Ref
 Quartile 2 4,278 (51) 0.91 (0.61−1.34) 0.621 0.95 (0.64−1.41) 0.807 0.96 (0.65−1.42) 0.827
 Quartile 3 4,136 (39) 0.90 (0.61−1.34) 0.600 0.95 (0.64−1.42) 0.817 0.97 (0.65−1.44) 0.890
 Quartile 4 2,862 (26) 0.69 (0.43−1.12) 0.131 0.77 (0.48−1.24) 0.286 0.80 (0.50−1.30) 0.373
Per 10 score increase 15,033 (176) 0.74 (0.51−1.07) 0.111 0.81 (0.55−1.17) 0.257 0.84 (0.57−1.22) 0.358
hPDI by quartiles
 Quartile 1 4,438 (78) Ref Ref Ref
 Quartile 2 3,620 (40) 0.63 (0.43−0.92) 0.016 0.67 (0.46−0.98) 0.038 0.67 (0.46−0.99) 0.043
 Quartile 3 3,237 (31) 0.54 (0.36−0.83) 0.004 0.60 (0.39−0.91) 0.015 0.61 (0.40−0.92) 0.020
 Quartile 4 3,738 (27) 0.41 (0.27−0.64) 0.000 0.48 (0.31−0.74) 0.001 0.50 (0.32−0.77) 0.002
Per 10 score increase 15,033 (176) 0.35 (0.23−0.54) <0.001 0.41 (0.26−0.63) <0.001 0.42 (0.27−0.66) <0.001
uPDI by quartiles
 Quartile 1 4,109 (32) Ref Ref Ref
 Quartile 2 4,796 (46) 1.22 (0.77−1.91) 0.395 1.15 (0.73−1.80) 0.548 1.12 (0.71−1.76) 0.623
 Quartile 3 3,063 (46) 1.90 (1.21−2.99) 0.005 1.74 (1.11−2.73) 0.017 1.67 (1.06−2.62) 0.028
 Quartile 4 3,065 (52) 2.13 (1.37−3.31) 0.001 1.88 (1.21−2.92) 0.005 1.81 (1.16−2.82) 0.009
Per 10 score increase 15,033 (176) 2.24 (1.50−3.36) <0.001 1.97 (1.31−2.96) 0.001 1.90 (1.26−2.88) 0.002

Table S10. Sensitivity analysisc of association between three plant-based diet indices and risks of EC.

Variables Sample (cases) Not adjusted model Minimally adjusted model Fully adjusted model
HR (95% CI) P HR (95% CI) P HR (95% CI) P
c, Excluded individuals who were diagnosed as EAC or other histological subtypes; EC, esophageal cancer; We explored the associations for PDI, hPDI, and uPDI with ESCC; Not adjusted model, PDI, hPDI, and uPDI are included separately; Minimally adjusted model, adjusted age and gender; Fully adjusted model, adjusted for age, gender, marital status, educational status, number of family members, annual income, smoking status, history of digestive diseases, and family history of cancer, and BMI categories; PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index; HR, hazard ratio; 95% CI, 95% confidence interval; EAC, esophageal adenocarcinoma.
PDI by quartiles
 Quartile 1 3,795 (49) Ref - Ref - Ref -
 Quartile 2 4,318 (48) 0.87 (0.58−1.30) 0.495 0.92 (0.61−1.36) 0.664 1.06 (0.66−1.68) 0.816
 Quartile 3 4,171 (46) 0.86 (0.58−1.29) 0.474 0.92 (0.61−1.37) 0.668 1.65 (1.04−2.62) 0.034
 Quartile 4 2,891 (24) 0.65 (0.40−1.07) 0.088 0.73 (0.45−1.19) 0.203 1.79 (1.14−2.82) 0.012
Per 10 score increase 15,175 (167) 0.70 (0.48−1.03) 0.072 0.77 (0.52−1.13) 0.177 0.80 (0.54−1.17) 0.247
hPDI by quartiles
 Quartile 1 4,482 (74) Ref Ref Ref
 Quartile 2 3,661 (38) 0.63 (0.42−0.93) 0.020 0.67 (0.45−0.99) 0.044 0.67 (0.46−1.00) 0.050
 Quartile 3 3,266 (29) 0.54 (0.35−0.82) 0.005 0.59 (0.38−0.91) 0.016 0.60 (0.39−0.92) 0.020
 Quartile 4 3,766 (26) 0.42 (0.27−0.66) 0.000 0.49 (0.31−0.76) 0.002 0.50 (0.32−0.79) 0.003
Per 10 score increase 15,175 (167) 0.35 (0.22−0.54) <0.001 0.41 (0.26−0.64) <0.001 0.42 (0.27−0.67) <0.001
uPDI by quartiles
 Quartile 1 4,131 (31) Ref Ref Ref
 Quartile 2 4,849 (42) 1.14 (0.72−1.82) 0.568 1.08 (0.68−1.72) 0.741 1.06 (0.66−1.68) 0.816
 Quartile 3 3,096 (44) 1.88 (1.19−2.97) 0.007 1.71 (1.08−2.72) 0.022 1.65 (1.04−2.62) 0.034
 Quartile 4 3,099 (50) 2.11 (1.35−3.31) 0.001 1.86 (1.19−2.91) 0.007 1.79 (1.14−2.82) 0.012
Per 10 score increase 15,175 (167) 2.26 (1.50−3.42) <0.001 1.98 (1.31−3.01) 0.001 1.92 (1.26−2.93) 0.003

Table S11. Sensitivity analysisd of association between three plant-based diet indices and risks of EC.

Variables Sample (cases) Not adjusted model Minimally adjusted model Fully adjusted model
HR (95% CI) P HR (95% CI) P HR (95% CI) P
d, Excluded alcoholic beverage for plant-based dietary patterns and adjusted it in the model; EC, esophageal cancer; Not adjusted model, PDI, hPDI, and uPDI are included separately; Minimally adjusted model, adjusted age and gender; Fully adjusted model, adjusted for age, gender, marital status, educational status, number of family members, annual income, smoking status, alcohol intake, history of digestive diseases, and family history of cancer, and BMI categories; PDI, overall plant-based diet index; hPDI, healthful plant-based diet index; uPDI, unhealthful plant-based diet index; HR, hazard ratio; 95% CI, 95% confidence interval.
PDI by quartiles
 Quartile 1 3,098 (32) Ref Ref Ref
 Quartile 2 4,023 (43) 1.05 (0.67−1.66) 0.828 1.06 (0.67−1.68) 0.789 1.02 (0.65−1.62) 0.920
 Quartile 3 4,372 (60) 1.35 (0.88−2.08) 0.170 1.33 (0.87−2.05) 0.189 1.27 (0.82−1.95) 0.287
 Quartile 4 3,691 (41) 1.10 (0.69−1.75) 0.687 1.06 (0.67−1.69) 0.800 0.96 (0.59−1.55) 0.858
Per 10 score increase 15,184 (176) 1.03 (0.71−1.49) 0.885 0.98 (0.68−1.43) 0.931 0.90 (0.61−1.32) 0.597
hPDI by quartiles
 Quartile 1 3,474 (56) Ref Ref Ref
 Quartile 2 3,481 (35) 0.63 (0.41−0.95) 0.030 0.64 (0.42−0.97) 0.036 0.64 (0.42−0.97) 0.036
 Quartile 3 3,579 (42) 0.73 (0.49−1.09) 0.127 0.72 (0.49−1.08) 0.115 0.70 (0.47−1.05) 0.085
 Quartile 4 4,650 (43) 0.58 (0.39−0.86) 0.007 0.58 (0.39−0.86) 0.007 0.55 (0.37−0.82) 0.004
Per 10 score increase 15,184 (176) 0.51 (0.32−0.81) 0.005 0.51 (0.32−0.81) 0.004 0.47 (0.29−0.75) 0.002
uPDI by quartiles
 Quartile 1 3,466 (36) Ref Ref Ref
 Quartile 2 3,239 (30) 0.89 (0.55−1.44) 0.625 0.89 (0.55−1.44) 0.631 0.93 (0.57−1.52) 0.781
 Quartile 3 4,861 (54) 1.06 (0.69−1.61) 0.800 1.08 (0.71−1.65) 0.711 1.16 (0.76−1.78) 0.495
 Quartile 4 3,618 (56) 1.46 (0.96−2.22) 0.077 1.57 (1.03−2.38) 0.062 1.65 (1.07−2.54) 0.024
Per 10 score increase 15,184 (176) 1.54 (1.01−2.33) 0.044 1.26 (0.88−1.79) 0.034 1.74 (1.13−2.66) 0.011

Individual food groups of plant-based diets and risk of EC

Correlation coefficients among different food groups ranged from −0.45 to 0.43 (Supplementary Figure S1). Supplementary Table S12 shows the results of multivariable Cox regression analyses of the associations between individual food groups of plant-based diets and the risk of EC. The analyses of individual food groups showed that higher intakes of fresh vegetable (HR: 0.68, 95% CI: 0.49−0.93) and legumes (HR: 0.82, 95% CI: 0.70−0.97) were associated with a lower risk of EC. In contrast, a higher intake of alcoholic beverages was associated with a greater risk of EC (HR: 1.49, 95% CI: 1.00−2.22).

Figure S1.

Figure S1

Spearman correlation analysis among food groups.

Table S12. HR (95% CI) of individual food group with risk of EC.

Food group Frequency HR 95% CI P
Adjusted for age, gender, marital status, educational status, number of family members, annual income, smoking status, history of digestive diseases, family history of cancer, and BMI categories. HR, hazard ratio; 95% CI, 95% confidence interval; EC, esophageal cancer.
Fresh vegetable <1 time/d 1
Daily 0.68 0.49−0.93 0.015
Fresh fruit <1 time/d 1
Daily 0.83 0.50−1.40 0.492
Meat/egg/dairy <1 time/d 1
Daily 0.54 0.24−1.22 0.139
Legumes <1 time/d 1
Daily 0.82 0.70−0.97 0.017
Spring onion,
garlic
<1 time/d 1
Daily 1.52 0.65−3.27 0.275
Staple food <1 time/d 1
Daily 0.43 0.11−1.73 0.234
Dried fruit and
vegetable
<1 time/d 1
Daily 0.92 0.67−1.25 0.592
Pickled vegetable <1 time/d 1
Daily 1.26 0.88−1.81 0.206
Fried food <1 time/d 1
Daily 0.94 0.55−1.61 0.831
Hot food <1 time/d 1
Daily 1.26 0.92−1.72 0.151
Mildewed food <1 time/d 1
Daily 1.27 0.18−9.08 0.812
Tea No 1
Yes 0.86 0.60−1.21 0.381
Alcoholic beverage No 1
Yes 1.49 1.00−2.22 0.047

Discussion

In this prospective cohort study involving Chinese males and females, a healthy plant-based diet captured by hPDI was inversely associated with the risk of EC, particularly ESCC. Conversely, an unhealthful plant-based diet, indicated by the uPDI, was found to be associated with a greater risk of EC. The associations were consistent across the age at baseline, gender, marital status, educational status, number of family members, annual income, smoking status, BMI, history of digestive diseases and family history of cancer. These findings underscore the significance of the healthiness and quality of plant-based diets in the development of EC, particularly ESCC. Notably, this is the first comprehensive study to investigate the association between PDI or hPDI or uPDI and EC, focusing on a Chinese cohort.

Numerous studies have explored the connection between plant-based diets and EC, but the results have been inconclusive, potentially due to the omission of considerations regarding the healthiness and quality of plant-based foods. In a previous study conducted in China, the vegetable and fruit pattern was shown to be associated with a reduced risk of ESCC (26). However, diet was not stratified by the health status of the plant foods. Similarly, other healthy dietary patterns, such as Mediterranean diets and Healthy Eating Indices, have been linked to a lower risk of EC. A higher adherence to the Mediterranean diet was associated with a reduced risk of ESCC in European cohorts (19). The Healthy Eating Index-2005 was inversely associated with the risk of EC in the U.S. National Institutes of Health (NIH)-AARP Diet and Health Study (27). Moreover, a recent meta-analysis reported inverse associations between various types of plant-based diets and EC, although these associations did not account for the quality or healthiness of plant-based foods (28).

A recent US population-based prospective cohort study showed that hPDI was associated with a reduced risk of EC, but this difference was not statistically significant (16). In contrast, our analysis revealed a significant inverse association between hPDI and EC, especially ESCC. Differences in the distribution of tumor subtypes across populations may partly explain these differentials (29). ESCC and EAC are the most common histological subtypes of EC. The distributions of ESCC and EAC differ, with EAC incidence rates being the highest in Northern Europe and North America and ESCC rates being the highest in Eastern and South-Central Asia and South Africa. In addition, our PDIs mainly included the dietary characteristics of the high-risk sites, which may be a more important reason for the inconsistency between results of this study and those of previous studies. Prior research has modified the PDIs framework by incorporating local Chinese dietary attributes (14,15).

In the 21st century, the typical rural Chinese diet predominantly comprises plant-based foods (30,31). In this context, fried foods primarily consist of items such as pancakes and fried dough sticks, while hot foods mainly encompass hot soups and noodles. Mildewed foods are often related to mouldy grains (32,33). Since earlier research has associated these foods with an increased risk of EC, they are categorized as components of an unhealthy plant-based diet group (20). The definition of staple food was based on the dietary characteristics of the two high-risk areas of China. During the survey period, the traditional staple foods in Linzhou and Feicheng were mixed grains, mainly consisting of corn and wheat (34). Early studies also noted that a high whole-grain diet is a dietary characteristic of residents in high-risk areas of EC in China (31). Based on these considerations, staple foods are included in healthy plant foods. The consumption of meat in the questionnaire referred to local common meats (pork, beef, rabbit, chicken, or duck) (35). Because the consumption of fish in Linxian and Feicheng, inland regions, is low, fish were not investigated as separate foods.

The observed associations of hPDI and uPDI with the risk of EC may be attributed to the individual food groups. According to our component analyses, consumption of vegetables and legumes exhibited an inverse association with the risk of EC. Vegetables are rich sources of dietary fibre, phytochemicals (such as flavonoids), and vitamins (such as vitamin C) and are known for their anti-inflammatory and antioxidant abilities. These bioactive compounds can mitigate chronic inflammation and DNA oxidative damage, both of which have been implicated in promoting cancer initiation and progression (36,37). The analysis of food components revealed that the consumption of legumes was linked to a reduced risk of EC, which aligns with findings from previous research. Since legumes exhibit very high trypsin inhibitory activity, these protease inhibitors strongly drive esophageal mucosa proliferation via epidermal growth factor and transforming growth factor-α, which are usually degraded in the presence of proteases (38). These constituents are known to exert anticancer effects through the reduction of oxidative stress and damage, as well as modulation of epigenetic aberrations. Taken together, these findings suggest that healthy plant-based diets might improve the health of the esophagus and contribute to the prevention of developing EC. Alcoholic beverages showed a weak positive association with the risk of EC in the component analyses. This is related to the production of reactive oxygen species by enzymes induced by the alcohol metabolite acetaldehyde and chronic alcohol consumption (39). Therefore, the healthiness and quality of plant foods should be emphasized in dietary recommendations for the general population.

The strengths of this study include the use of prospective cohorts, a large sample size, and up to 17 years of follow-up. Additionally, this is the first study to evaluate the relationship of PDIs with EC and ESCC incidence, focusing on a Chinese cohort. This study has several limitations. First, it would be difficult to compare the PDIs in this study with the original PDIs. The food classification for the calculation of the PDIs score is based on the dietary habits of high-risk areas for EC in China. In addition, we used intake frequency rather than servings or quintiles of intake per day to score the diets. Several studies have provided evidence supporting the reliability and validity of utilizing nonquantitative food frequency questionnaires for assessing dietary patterns (21-23). However, it is important to note that the food questionnaire used in our study might not be standardized to the extent required for direct comparisons with other nutritional studies. We were also unable to estimate or adjust for total energy intake. Second, dietary information was collected only at the baseline, and individuals may have altered their dietary habits during the 17-year follow-up period. Therefore, our results might be subject to nondifferential bias. Nonetheless, it has been revealed that the approach using only baseline information leads to a weaker association than the approach using cumulative averages (40). Third, although information on BMI and tobacco smoking status was available, data on physical activity and other lifestyle factors were lacking. Finally, the compliance rate of endoscopic screening was 49.36%, which may have resulted in selection bias. However, it is difficult to persuade asymptomatic residents to participate in an invasive screening program. In a population-based cohort, a compliance rate of 49.36% was already a tough goal (41).

Conclusions

This study established a significant association between a healthy plant-based dietary pattern and a reduced risk of EC, particularly ESCC. Conversely, an unhealthy plant-based dietary pattern was associated with a greater risk of EC, including ESCC. These findings emphasize the importance of improving the quality of plant-based diets for EC prevention.

Acknowledgements

This study was supported by grants from the Beijing Nova Program (No. Z201100006820069); CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2021-I2M-1-023, 2021-I2M-1-010) and Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star).

Contributor Information

Fen Liu, Email: liufen05@ccmu.edu.cn.

Shaoming Wang, Email: wangshaoming@cicams.ac.cn.

Wenqiang Wei, Email: weiwq@cicams.ac.cn.

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