Associations between dietary polyphenols and risks of gastric precancerous lesions and cancer

Table 1 Baseline participant characteristics and polyphenols intake by pathological diagnosis, mean ± SD/n (%)

Characteristics	Overall (n = 8507)	Normal or superficial gastritis (n = 1570)	Gastric precancerous lesions (n = 6713)	Gastric cancer (n = 224)
Male	4613 (54.2)	745 (47.5)	3693 (55.0)	175 (78.1)
Age (years)	51.93 ± 7.85	50.71 ± 7.44	52.02 ± 7.87	57.69 ± 7.36
Farmer	7789 (91.6)	1363 (86.8)	6210 (92.5)	216 (96.4)
Current smoking	2932 (34.5)	446 (28.4)	2395 (35.7)	91 (40.6)
Current drinking	389 (4.6)	52 (3.3)	329 (4.9)	8 (3.6)
Education level
Illiterate	1564 (18.4)	244 (15.5)	1278 (19.0)	42 (18.8)
Primary school	3135 (36.9)	581 (37.0)	2460 (36.6)	94 (42.0)
Secondary high school	3778 (44.4)	739 (47.1)	2954 (44.0)	85 (37.9)
Profession education and above	30 (0.4)	6 (0.4)	21 (0.3)	3 (1.3)
Annual household income (Chinese yuan/year)
Low (< 20000)	3628 (42.6)	601 (38.3)	2914 (43.4)	113 (50.4)
Moderate (20000-30000)	2076 (24.4)	309 (19.7)	1713 (25.5)	54 (24.1)
High (> 30000)	2803 (32.9)	660 (42.0)	2086 (31.1)	57 (25.4)
BMI (kg/m2)
Underweight (< 18.5)	204 (2.4)	33 (2.1)	148 (2.2)	23 (10.3)
Normal-weight (18.5-24.0)	4270 (50.2)	793 (50.5)	3354 (50.0)	123 (54.9)
Overweight (24.0-28.0)	3325 (39.1)	597 (38.0)	2662 (39.7)	66 (29.5)
Obesity (≥ 28.0)	708 (8.3)	147 (9.4)	549 (8.2)	12 (5.4)
H. pylori infection	4557 (53.6)	684 (43.6)	3764 (56.1)	109 (48.7)
Digestive cancer family history	61 (0.7)	9 (0.6)	51 (0.8)	1 (0.4)
Energy intake (kcal/day), median (IQR)	1609.08 (1237.58, 2117.65)	1526.45 (1151.99, 1988.92)	1626.43 (1253.64, 2142.13)	1687.51 (1298.11, 2335.54)
Polyphenols intake, median (IQR)
Flavonoids (mg/1000 kcal/day)	102.30 (76.96, 136.94)	101.56 (74.83, 134.38)	102.37 (77.63, 137.15)	102.92 (73.49, 144.11)
Phenolic acids (mg/1000 kcal/day)	76.76 (61.43, 95.84)	76.56 (60.38, 95.65)	76.83 (61.72, 95.84)	75.40 (60.96, 99.27)
Lignans (mg/1000 kcal/day)	30.26 (18.24, 45.74)	30.94 (18.98, 46.36)	30.11 (17.97, 45.53)	30.89 (18.27, 48.09)
Stilbenes (μg/1000 kcal/day)	5.21 (0.28, 13.40)	6.74 (0.33, 15.75)	4.90 (0.27, 12.77)	4.25 (0.00, 12.06)

BMI: Body mass index; H. pylori: Helicobacter pylori; IQR: Interquartile range.

Table 2 Odds ratios and 95% confidence intervals for the associations of dietary polyphenol intake with gastric precancerous lesions and gastric cancer

Polyphenol subclass	Gastric precancerous lesions (n = 6713)						Gastric cancer (n = 224)
	Crude model		Model 1		Model 2		Crude model		Model 1		Model 2
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Flavonoids (mg/1000 kcal/day)
T1 (2.26-85.70)	Reference		Reference		Reference		Reference		Reference		Reference
T2 (85.70-123.21)	1.10 (0.96-1.26)	0.163	1.13 (0.99-1.30)	0.077	1.09 (0.95-1.25)	0.224	0.86 (0.60-1.22)	0.389	1.10 (0.74-1.64)	0.647	0.99 (0.65-1.49)	0.957
T3 (123.21-1488.59)	1.11 (0.97-1.27)	0.129	1.12 (0.98-1.29)	0.105	1.06 (0.92-1.22)	0.402	1.13 (0.81-1.58)	0.469	1.39 (0.96-2.03)	0.085	1.25 (0.85-1.85)	0.258
P for trend		0.127		0.104		0.406		0.475		0.085		0.250
Log2 (continues)	1.11 (1.03-1.20)	0.004	1.12 (1.04-1.21)	0.004	1.08 (0.99-1.16)	0.072	1.11 (0.92-1.35)	0.267	1.25 (1.02-1.55)	0.034	1.15 (0.92-1.43)	0.212
Phenolic acids (mg/1000 kcal/day)
T1 (7.26-67.10)	Reference		Reference		Reference		Reference		Reference		Reference
T2 (67.10-88.28)	1.16 (1.02-1.33)	0.028	1.18 (1.03-1.35)	0.020	1.11 (0.97-1.28)	0.141	0.96 (0.68-1.35)	0.813	1.07 (0.72-1.57)	0.749	0.93 (0.63-1.38)	0.725
T3 (88.28-494.41)	1.07 (0.93-1.22)	0.336	1.09 (0.95-1.25)	0.227	0.93 (0.80-1.07)	0.303	0.96 (0.68-1.35)	0.815	1.10 (0.75-1.61)	0.619	0.77 (0.50-1.18)	0.234
P for trend		0.331		0.225		0.344		0.812		0.618		0.237
Log2 (continues)	1.03 (0.93-1.13)	0.607	1.04 (0.94-1.15)	0.416	0.90 (0.8-1.01)	0.073	1.04 (0.81-1.34)	0.773	1.17 (0.89-1.56)	0.268	0.89 (0.65-1.23)	0.493
Lignans (mg/1000 kcal/day)
T1 (0.22-22.05)	Reference		Reference		Reference		Reference		Reference		Reference
T2 (22.05-39.22)	0.92 (0.80-1.05)	0.233	0.96 (0.83-1.10)	0.532	0.90 (0.78-1.04)	0.151	0.88 (0.63-1.25)	0.487	1.02 (0.69-1.51)	0.919	0.94 (0.63-1.39)	0.745
T3 (39.22-439.33)	0.89 (0.78-1.02)	0.085	0.93 (0.81-1.07)	0.287	0.83 (0.72-0.96)	0.010	0.91 (0.65-1.28)	0.580	1.29 (0.88-1.90)	0.196	1.12 (0.75-1.66)	0.591
P for trend		0.086		0.288		0.010		0.584		0.198		0.589
Log2 (continues)	0.97 (0.92-1.02)	0.285	0.99 (0.94-1.05)	0.788	0.94 (0.89-1.00)	0.053	0.96 (0.84-1.10)	0.518	1.09 (0.94-1.28)	0.251	1.04 (0.89-1.22)	0.647
Stilbenes (μg/1000 kcal/day)
T1 (0.00-1.33)	Reference		Reference		Reference		Reference		Reference		Reference
T2 (1.33-9.26)	1.01 (0.88-1.17)	0.852	1.09 (0.94-1.26)	0.241	1.04 (0.90-1.21)	0.555	0.84 (0.60-1.18)	0.320	0.95 (0.65-1.40)	0.805	0.90 (0.61-1.32)	0.584
T3 (9.26-3144.54)	0.73 (0.64-0.84)	< 0.001	0.82 (0.71-0.94)	0.005	0.78 (0.67-0.89)	< 0.001	0.59 (0.42-0.84)	0.003	0.82 (0.56-1.22)	0.334	0.76 (0.51-1.12)	0.167
P for trend		< 0.001		0.003		< 0.001		0.003		0.338		0.168
Log2 (continues)	0.95 (0.93-0.97)	< 0.001	0.96 (0.94-0.99)	0.002	0.95 (0.93-0.97)	< 0.001	0.92 (0.86-0.97)	0.006	0.98 (0.91-1.05)	0.489	0.96 (0.89-1.03)	0.248

Crude model was adjusted for total energy intake and standardized to intakes per 1000 kcal. Model 1 further adjusted for sex, age, education level, occupation, annual household income, smoking status, alcohol consumption, body mass index, Helicobacter pylori status, and family history of digestive cancers. Model 2 additionally included all other polyphenol subclasses to account for potential mutual confounding among different polyphenol types. OR: Odds ratio; CI: Confidence interval.

Table 3 Odds ratios and 95% confidence intervals for the associations of dietary polyphenol intake with subtypes of gastric precancerous lesions

Polyphenol subclass	Chronic atrophic gastritis (n = 3070)						Intestinal metaplasia (n = 1612)						Low-grade dysplasia (n = 2031)
	Crude model		Model 1		Model 2		Crude model		Model 1		Model 2		Crude model		Model 1		Model 2
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Flavonoids (mg/1000 kcal/day)
T1 (2.26-85.70)	Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference
T2 (85.70-123.21)	1.06 (0.91-1.22)	0.477	1.10 (0.94-1.28)	0.229	1.07 (0.91-1.25)	0.403	1.19 (1.00-1.40)	0.048	1.25 (1.05-1.50)	0.012	1.23 (1.02-1.47)	0.026	1.10 (0.94-1.29)	0.238	1.20 (1.01-1.43)	0.038	1.12 (0.94-1.34)	0.194
T3 (123.21-1488.59)	1.10 (0.95-1.27)	0.224	1.12 (0.96-1.30)	0.151	1.08 (0.93-1.26)	0.324	1.08 (0.91-1.29)	0.352	1.10 (0.92-1.31)	0.314	1.07 (0.89-1.28)	0.474	1.15 (0.98-1.35)	0.089	1.18 (0.99-1.40)	0.061	1.05 (0.88-1.25)	0.597
P for trend		0.224		0.150		0.328		0.340		0.302		0.488		0.088		0.061		0.606
Log2 (continues)	1.06 (0.98-1.15)	0.143	1.08 (0.99-1.17)	0.079	1.05 (0.97-1.15)	0.248	1.13 (1.03-1.24)	0.010	1.16 (1.05-1.27)	0.004	1.13 (1.02-1.25)	0.017	1.19 (1.08-1.30)	< 0.001	1.20 (1.09-1.33)	< 0.001	1.10 (0.99-1.22)	0.070
Phenolic acids (mg/1000 kcal/day)
T1 (7.26-67.10)	Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference
T2 (67.10-88.28)	1.13 (0.97-1.31)	0.113	1.15 (0.99-1.34)	0.077	1.11 (0.95-1.29)	0.197	1.13 (0.96-1.34)	0.143	1.13 (0.95-1.35)	0.161	1.06 (0.88-1.26)	0.549	1.25 (1.06-1.47)	0.008	1.32 (1.11-1.57)	0.002	1.20 (1.00-1.43)	0.046
T3 (88.28-494.41)	1.07 (0.93-1.24)	0.355	1.09 (0.94-1.26)	0.279	0.99 (0.84-1.16)	0.869	0.91 (0.77-1.08)	0.282	0.93 (0.78-1.11)	0.430	0.75 (0.62-0.91)	0.004	1.20 (1.02-1.41)	0.025	1.30 (1.09-1.54)	0.003	1.00 (0.83-1.20)	0.961
P for trend		0.352		0.276		0.909		0.311		0.456		0.006		0.027		0.003		0.994
Log2 (continues)	1.02 (0.92-1.14)	0.686	1.04 (0.93-1.16)	0.483	0.95 (0.84-1.08)	0.465	0.92 (0.81-1.05)	0.223	0.94 (0.83-1.08)	0.386	0.78 (0.67-0.9)	0.001	1.12 (0.99-1.26)	0.062	1.18 (1.04-1.34)	0.011	0.94 (0.81-1.08)	0.368
Lignans (mg/1000 kcal/day)
T1 (0.22-22.05)	Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference
T2 (22.05-39.22)	0.93 (0.80-1.08)	0.326	0.97 (0.83-1.13)	0.666	0.94 (0.80-1.09)	0.410	0.95 (0.80-1.12)	0.534	0.99 (0.83-1.18)	0.933	0.93 (0.78-1.11)	0.422	0.89 (0.75-1.05)	0.156	0.94 (0.79-1.11)	0.449	0.87 (0.73-1.04)	0.121
T3 (39.22-439.33)	0.88 (0.75-1.02)	0.082	0.92 (0.79-1.08)	0.302	0.87 (0.74-1.02)	0.076	0.83 (0.70-0.99)	0.036	0.89 (0.74-1.06)	0.197	0.80 (0.66-0.96)	0.017	0.95 (0.81-1.12)	0.554	1.02 (0.86-1.22)	0.780	0.86 (0.72-1.03)	0.106
P for trend		0.082		0.302		0.076		0.036		0.196		0.017		0.572		0.763		0.108
Log2 (continues)	0.98 (0.92-1.04)	0.443	1 (0.94-1.06)	0.954	0.97 (0.91-1.04)	0.386	0.93 (0.87-0.99)	0.035	0.96 (0.89-1.03)	0.234	0.91 (0.85-0.98)	0.017	1.00 (0.93-1.07)	0.945	1.03 (0.96-1.11)	0.342	0.96 (0.89-1.03)	0.279
Stilbenes (μg/1000 kcal/day)
T1 (0.00-1.33)	Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference		Reference
T2 (1.33-9.26)	1.05 (0.90-1.23)	0.510	1.11 (0.95-1.30)	0.198	1.09 (0.93-1.28)	0.300	0.91 (0.77-1.08)	0.293	0.98 (0.82-1.17)	0.785	0.94 (0.78-1.13)	0.497	1.05 (0.89-1.24)	0.573	1.14 (0.96-1.36)	0.139	1.05 (0.88-1.26)	0.574
T3 (9.26-3144.54)	0.82 (0.71-0.95)	0.009	0.90 (0.77-1.05)	0.173	0.87 (0.75-1.02)	0.089	0.53 (0.45-0.63)	< 0.001	0.61 (0.51-0.73)	< 0.001	0.58 (0.48-0.69)	< 0.001	0.79 (0.68-0.93)	0.005	0.88 (0.74-1.04)	0.138	0.78 (0.66-0.94)	0.007
P for trend		0.007		0.136		0.067		< 0.001		< 0.001		< 0.001		0.004		0.112		0.005
Log2 (continues)	0.97 (0.94-0.99)	0.010	0.98 (0.95-1.00)	0.105	0.97 (0.94-0.99)	0.040	0.90 (0.87-0.92)	< 0.001	0.92 (0.89-0.95)	< 0.001	0.91 (0.87-0.94)	< 0.001	0.96 (0.94-0.99)	0.011	0.97 (0.94-0.99)	0.085	0.95 (0.92-0.98)	0.002

Crude model was adjusted for total energy intake and standardized to intakes per 1000 kcal. Model 1 further adjusted for sex, age, education level, occupation, annual household income, smoking status, alcohol consumption, body mass index, Helicobacter pylori status, and family history of digestive cancers. Model 2 additionally included all other polyphenol subclasses to account for potential mutual confounding among different polyphenol types. OR: Odds ratio; CI: Confidence interval.

Table 4 Sensitivity analysis of the associations between dietary polyphenol and the risks of gastric cancer and gastric precancerous lesions based on quartiles of polyphenol intake

Polyphenol subclass	Chronic atrophic gastritis (n = 3070)		Intestinal metaplasia (n = 1612)		Low-grade dysplasia (n = 2031)		Gastric cancer (n = 224)
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Flavonoids (mg/1000 kcal/day)
Q1 (2.26-76.96)	Reference		Reference		Reference		Reference
Q2 (76.96-102.30)	1.09 (0.91-1.30)	0.365	1.40 (1.13-1.72)	0.002	1.33 (1.09-1.63)	0.005	0.80 (0.50-1.27)	0.349
Q3 (102.30-136.94)	1.02 (0.85-1.21)	0.864	1.14 (0.93-1.41)	0.208	1.25 (1.02-1.54)	0.030	0.93 (0.58-1.48)	0.758
Q4 (136.94-1488.59)	1.10 (0.92-1.31)	0.307	1.21 (0.98-1.50)	0.074	1.09 (0.89-1.35)	0.400	1.22 (0.79-1.88)	0.378
P for trend		0.455		0.287		0.556		0.303
Phenolic acids (mg/1000 kcal/day)
Q1 (7.26-61.43)	Reference		Reference		Reference		Reference
Q2 (61.43-76.76)	1.15 (0.96-1.37)	0.133	1.19 (0.97-1.46)	0.102	1.11 (0.91-1.37)	0.294	1.28 (0.82-2.00)	0.277
Q3 (76.76-95.84)	1.05 (0.88-1.25)	0.598	0.96 (0.78-1.18)	0.666	1.03 (0.84-1.27)	0.741	0.69 (0.43-1.12)	0.133
Q4 (95.84-494.41)	0.99 (0.82-1.20)	0.945	0.74 (0.59-0.93)	0.010	0.99 (0.80-1.23)	0.917	0.87 (0.53-1.42)	0.582
P for trend		0.762		0.003		0.770		0.200
Lignans (mg/1000 kcal/day)
Q1 (0.22-18.24)	Reference		Reference		Reference		Reference
Q2 (18.24-30.26)	0.95 (0.79-1.14)	0.572	0.82 (0.66-1.01)	0.057	0.79 (0.64-0.96)	0.020	0.89 (0.56-1.40)	0.608
Q3 (30.26-45.74)	0.89 (0.74-1.07)	0.216	0.80 (0.65-0.98)	0.033	0.84 (0.68-1.02)	0.084	0.99 (0.63-1.56)	0.965
Q4 (45.74-439.33)	0.88 (0.73-1.06)	0.178	0.76 (0.61-0.94)	0.010	0.80 (0.65-0.99)	0.041	1.14 (0.72-1.81)	0.568
P for trend		0.137		0.012		0.082		0.489
Stilbenes (μg/1000 kcal/day)
Q1 (0.00-0.28)	Reference		Reference		Reference		Reference
Q2 (0.28-5.21)	1.20 (1.00-1.45)	0.051	1.11 (0.90-1.36)	0.341	1.25 (1.02-1.54)	0.033	1.05 (0.68-1.64)	0.818
Q3 (5.21-13.40)	0.96 (0.80-1.14)	0.633	0.76 (0.62-0.93)	0.009	0.81 (0.66-1.00)	0.047	0.74 (0.48-1.16)	0.193
Q4 (13.40-3144.54)	0.88 (0.74-1.06)	0.178	0.58 (0.47-0.72)	< 0.001	0.82 (0.67-1.00)	0.055	0.80 (0.51-1.26)	0.344
P for trend		0.031		< 0.001		0.001		0.176

All models were adjusted for sex, age, education level, occupation, annual household income, smoking status, alcohol consumption, body mass index, Helicobacter pylori status, family history of digestive cancers, and all other polyphenol subclasses to account for potential mutual confounding among different polyphenol types. The intake of each subclass polyphenol was standardized by total energy intake (per 1000 kcal).