Table 1. Characteristics of included studies.

Study	Region and design	Cases/cohort or controls	Follow-up (years)	Flavonoid type	Intake comparison	Cancer site	RR/OR/HR (95% CI)	Adjustments
Arts,2002 [33]	USA; Cohort	5,038/34,651	13	Total catechin: ((+)-catechin; (−)-epicatechin; (+)-gallocatechin; (−)-epigallocatechin; (−)-epicatechin gallate; (−)-epigallocatechin gallate)	75.1 VS 3.6 mg/d	Any cancer combined	0.97 (0.88–1.06)	age, total energy intake, body mass index, waist-to-hip ratio, physical activity, pack-years of smoking, smoking status, number of years since quit smoking, alcohol intake, and total fruit and vegetable consumption
					24.7 VS 3.6 mg/d	Upper digestive tract	0.71 (0.46-1.11)
					75.1 VS 3.6 mg/d	Colon	1.10 (0.85–1.44)
					24.7 VS 3.6 mg/d	Rectum	0.55 (0.32–0.95)
					24.7 VS 3.6 mg/d	Pancreas	0.74 (0.46–1.20)
					75.1 VS 3.6 mg/d	Bronchus and lung	0.94 (0.72–1.23)
					24.7 VS 3.6 mg/d	Hematopoietic	0.65 (0.43–0.98)
					75.1 VS 3.6 mg/d	Breast	1.04 (0.84–1.28)
					24.7 VS 3.6 mg/d	Uterus	1.00 (0.73–1.36)
					24.7 VS 3.6 mg/d	Ovary	0.73 (0.44–1.24)
					24.7 VS 3.6 mg/d	Kidney and renal pelvis	0.73 (0.40–1.32)
					14.8 VS 3.6 mg/d	Bladder	1.12 (0.65–1.93)
					24.7 VS 3.6 mg/d	Non-Hodgkin's lymphoma	1.26 (0.87–1.85)
Zamora-Ros,2014 [69]	Europe; Cohort	1,575/477,312	11	Flavan-3-ol monomers	>376.0 VS <19.3 mg/d	Bladder	0.90 (0.73–1.11)	sex, age (1 year) and centre and adjusted for energy, smoking intensity, BMI, physical activity, alcohol intake and highest educational level.
Bosetti,2005 [70]	Italy; Case control (hospital based)	2,569/2,588	-	Flavan-3-ols	>79.7 VS 18.1 mg/d	Breast total	0.86 (0.71-1.05)
					>18.1 VS 18.1 mg/d	Breast premenopause	0.94 (0.85-1.05)	age, study center, education, parity, alcohol consumption, and non-alcohol energy intake
						Breast postmenopause	0.92 (0.84-1.00)
Fink,2007 [71]	USA; Case control (population based)	1,434 /1,440	-	Flavan-3-ols	≥268.0 VS ≤6.5 mg/d	Breast total	0.85 (0.67-1.08)	age and energy intake
					≥264.2 VS ≤5.1 mg/d	Breast premenopause	1.21 (0.78-1.86)
					≥278.0 VS ≤7.6 mg/d	Breast postmenopause	0.74 (0.55-0.99)
Peterson,2003 [72]	Greece; Case control (hospital based)	820 / 1,548	-	Flavan-3-ols	Per 1 s.d. increment	Breast	0.93 (0.78 −1.11)	age, place of birth, parity, age at first pregnancy, age at menarche, menopausal status, body mass index, total energy intake, alcohol consumption, fruit and vegetable consumption and mutually between flavonoid categories
Sanchez,2009 [73]	Mexico; Case control (hospital based)	141/141	-	Flavan-3-ols	10.6–45.9 VS 0.2–5.9 mg/d	Breast total	0.80 (0.38-1.70)	age, total energy consumption, lifetime lactation (months) and menopausal stage
						Breast premenopause	1.22 (0.48-3.08)
						Breast postmenopause	0.63 (0.25-1.62)
						Breast higher alcohol	2.28 (1.19–4.36)	age, BMI, intervention group, alcohol intake, number of dietary records, energy intake, height, physical activity, smoking status, educational level, family history of breast cancer, menopausal status, use of hormonal treatment for menopause, and number of children
Touvier,2013 [34]	France; Cohort	152/4,141	12.6	catechins	151.5 VS 61.2 mg/d
						Breast low alcohol	0.48 (0.22–1.05)
Wang,2014 a [74]	USA; Cohort	2116 /56,630	8.5	Flavan-3-ols	>36.7–410 VS ≤9.0 mg/d	Breast	0.98 (0.86–1.12)	age, family history of breast cancer, history of breast cyst, weight gain since age 18 y, education, combination of parity and age at first live birth, ethanol consumption, smoking history, total energy intake in quintile, age at menopause and history of hormone replacement therapy
Zamora-Ros,2013 a [75]	Europe; Cohort	11,576/334,850	11.5	Flavan-3-ol monomers	>379.8 VS <18.2 mg/d	Breast total	1.01 (0.93–1.09)	age, menopausal status, weight, height, smoking status, educational level, physical activity, age at menarche, age at first full-term birth, ever use of contraceptive, use of hormones, age at menopause, energy intake, alcohol intake and fibre intake
						Breast premenopause	0.96 (0.82–1.13)
						Breast postmenopause	1.00 (0.90–1.11)
Kyle,2010 [76]	UK; Case control (population based)	261/404	-	Flavan-3-ols	>188.81 VS <67.10 mg/d	Colorectum	0.6 (0.4 - 1.0)	energy, age at diagnosis, family history, non-steroidal anti-inflammatory drugs, aspirin, Mn, riboflavin, vitamin C, folate
						Colon	0.5 (0.3 - 1.0)
						Rectum	0.7 (0.4 - 1.4)
Mursu,2008 [77]	Finland; Cohort	Lung 62, prostate 138, and colorectum 55 /2590	16.2	Flavan-3-ols	Quartile 4 VS 1	Colorectum	1.37 (0.65–2.89)	age, examination years, BMI, smoking status, pack-years of smoking, physical activity, intakes of alcohol, total fat, saturated fat, energy adjusted intake of fiber, vitamin C and E
						Lung	0.24 (0.09–0.64)
						Prostate	1.13 (0.70–1.82)
Nimptsch,2016 [44]	USA cohort	Male: 1061/42478 Female: 1458/76364	26	Flavan-3-ols	Male: 128±88 VS 11.9±7.2 mg/d Female: 149.5±95.1 VS 9.3±5.1 mg/d	Colorectum	1.07 (0.95, 1.21)	age, pack-years of smoking before age 30 y, history of colorectal cancer in a parent or sibling, history of endoscopy, regular aspirin use, BMI, physical activity, alcohol consumption, total calories, energy-adjusted total vitamin D intake, total calcium intake, red meat intake, and processed meat intake
						Colorectum male	1.12 (0.92, 1.36)
						Colorectum female	1.04 (0.88, 1.23)
						Colon	1.09 (0.93, 1.27)
						Colon male	1.20 (0.96, 1.50)
						Colon female	1.02 (0.85, 1.23)
						Rectum	1.02 (0.78, 1.34)
						Rectum male	0.90 (0.60, 1.35)
						Rectum female	1.13 (0.79, 1.63)
Rossi,2006 [78]	Italy; Case control (hospital based)	1953 /4154	-	Flavan-3-ols	>88.5 VS <20.8 mg/d	Colorectum	0.98 (0.82-1.18)	age, sex, study center, family history, education, alcohol consumption, body mass index, occupational physical activity, and energy intake
						Colon	1.12 (0.90-1.39)
						Rectum	0.81 (0.62-1.06)
Simons,2009 [35]	Netherland; Case-cohort	Male: 1,444/2,191 Female: 1,041/2,247	13.3	Total catechin ((+)-catechin; (−)-epicatechin; (+)-gallocatechin; (−)-epigallocatechin; (−)-epicatechin gallate; (−)-epigallocatechin gallate)	84.3–290.1 VS <24.2 mg/d	Colorectum male	0.99 (0.77–1.25)	age, family history of colorectal cancer, smoking status, alcohol intake, occupational physical activity at longest held job, BMI and processed meat intake
						Colon male	1.13 (0.86–1.48)
						Rectum male	0.80 (0.56–1.14)
					95.9–287.3 VS <36.2 mg/d	Colorectum female	0.79 (0.61–1.02)
						Colon female	0.82 (0.62–1.09)
						Rectum female	0.80 (0.48–1.33)
Theodoratou, 2007 [79]	Scotland; Case control (population based)	1,456/1,456	-	Flavan-3-ols	>162.1 VS 0-42.6 mg/d	Colorectum	0.81 (0.65-1.01)	age, gender, family history, total energy intake, total fiber intake, alcohol intake, NSAID intake, smoking, BMI, and physical activity
						Colon	0.79 (0.59-1.07)
						Rectum	0.87 (0.62-1.24)
Zamora-Ros, 2013 b [80]	Spain; Case control (hospital based)	424 /401	-	Flavan-3-ols	>12.9 VS <4.9 (mg/1,000 kcal day)	Colorectum	0.79 (0.49 - 1.28)	sex, age, BMI, energy intake, alcohol, fiber intake, red and processed meat intake, tobacco consumption, physical activity, regular drugs and family history
						Colon	0.78 (0.45–1.34)
						Rectum	0.78 (0.39–1.54)
Bobe,2009 [81]	USA; Case control (population based)	161EAC 114ESCC / 678 white 218ESCC /557 black	-	Flavan-3-ols	>60.6 VS <10.3 mg/1,000 kcal >49.4 VS <6.17 mg/1,000 kcal	Esophagus White-EAC	1.22 (0.60–2.49)	smoking, geographical area, age, BMI, hot tea, hard liquor and beer, moonshine consumption (only for black men), red wine, white wine consumption (except for ESCC in white men), caloric intake, education (only for black men) and income
						Esophagus White-ESCC	0.95 (0.36–2.52)
						Esophagus Black-ESCC	0.78 (0.36–1.68)
Petrick,2015 [82]	USA; Case control (population based)	EAC 274, ESCC 191, GCA 248, OGA 341 / 622	-	Flavan-3-ols	≥130.7 VS 0–10.29 mg/d	Esophagus EAC	1.02 (0.69-1.51)	age, sex, race, geographic center, cigarette smoking and dietary energy intake
						Esophagus ESCC	0.98 (0.60-1.59)
						Stomach GCA	1.17 (0.77-1.78)
						Stomach OGA	1.30 (0.88-1.92)
Rossi,2007 a [83]	Italy; Case control (hospital based)	304/743	-	Flavan-3-ols	>109.1 VS <32.6 mg/d	Esophagus ESCC	1.06 (0.58–1.94)	age, sex, study center, education, alcohol consumption, tobacco smoking, BMI and energy intake
Vermeulen, 2013 [84]	Europe; Cohort	341 / 477,312	11	Flavan-3-ol monomers	Quartile 4 VS 1	Esophagus	0.86 (0.58-1.27)	age, sex, energy intake, BMI, smoking intensity, educational level, physical activity, alcohol, red and processed meat intake, fiber, vitamin C and carotenoids
Lagiou,2004 a [85]	Greece; Case control (hospital based)	110/100	-	Flavan-3-ols	Per 1 s.d. increment	Stomach	1.04 (0.68–1.58)	age, gender, place of birth, BMI, height, years of education, smoking habits and duration of smoking, alcohol consumption, total energy intake, fruit and vegetable consumption
Rossi,2010 [86]	Italy; Case control (hospital based)	230/547	-	Flavan-3-ols	>79.2 VS <21.6 mg/d	Stomach	0.75 (0.45–1.23)	sex, age, education, year of interview, BMI, tobacco smoking, and total energy intake
Woo,2014 [87]	Korea; Case control (hospital based)	334/334	-	Flavan-3-ols	39.7 VS 3.2 mg/d	Stomach	0.73 (0.45–1.18)	total energy intake, H. pylori, age, sex, education, smoking status, alcohol consumption, BMI, physical activity, consumption of pickled vegetable and red and processed meat, fruits and vegetable consumption
						Stomach male	0.78 (0.41–1.49)
						Stomach female	0.65 (0.27–1.57)
Zamora-Ros, 2012 [88]	Europe; Cohort	683/ 477,312	11	Flavan-3-ol monomers	>199.9 VS <26.1 mg/d >241.6 VS <21.1 mg/d	Stomach male	0.98 (0.68, 1.40)	center, sex, age, educational level, smoking status, physical activity, BMI, alcohol and energy intake, daily consumption of fruit, vegetables, and red and processed meat
						Stomach female	0.55 (0.34, 0.88)
Rossi, 2007 b [89]	Italy; Case control (hospital based)	805/2,081	-	Flavan-3-ols	>99.6 VS <23.3 mg/d	Oropharynx	0.84 (0.60-1.18)	sex, age, study center, smoking, alcohol drinking, education, BMI, and non–alcohol energy intake
Garavello, 2007 [90]	Italy; Case control (hospital based)	460/1,088	-	Flavan-3-ols	>110.4 VS <31.2 mg/d	Larynx	0.64 (0.41–0.99)	age, sex, study center, education, alcohol consumption, smoking, BMI, occupational physical activity and non-alcohol energy intake
Lagiou,2008 [91]	Greece; Case control (hospital based)	250 HBV and/or HCV positive, 83 HBV and HCV negative /360	-	Flavan-3-ols	>66.3 VS <25.3 mg/d	Liver virus positive	1.17 (0.65–2.12)	gender, age, education, tobacco smoking, and total energy intake
						Liver virus negative	1.14 (0.50–2.58)
Zamora-Ros, 2013 c [92]	Europe; Cohort	191/477,206	11	Flavan-3-ol monomers	>134.8 VS <28.2 mg/d	Liver	0.65 (0.39-1.07)	center, sex, age, total energy, education, smoke intensity, alcohol lifetime and alcohol baseline, BMI, self-reported diabetes at baseline, physical activity, fiber and coffee intake
Arts, 2001 [36]	Netherland; Cohort	96 Epithelial cancer, 42 lung cancer /728	10	Total catechin((+)-catechin; (−)-epicatechin; (+)-gallocatechin; (−)-epigallocatechin; (−)-epicatechin gallate; (−)-epigallocatechin gallate)	85.8–355.4 VS 0–49.0 mg/d	Epithelial cancer combined	0.94 (0.56–1.59)	age, physical activity, total energy intake, alcohol intake, smoking status, pack-years of smoking, BMI, coffee, fiber, vitamin C, vitamin E, beta-carotene
						Lung	0.92 (0.41–2.07)
Christensen, 2012 [93]	Canada; Case control (population based)	1,061/1,425	-	Flavan-3-ols	Male: >271.0 VS <12.6 mg/d Female: >249.1 VS <8.7 mg/d	Lung	1.06 (0.81–1.39)	age, sex, number of school years, mean census tract family income, ethnic group, respondent status, comprehensive smoking indicator, occupational exposure to carcinogens, BMI, number of alcoholic drinks/day and total energy intake
						Lung smokers	1.08 (0.79–1.49)
						Lung nonsmokers	1.01 (0.56–1.81)
						Lung male	1.18 (0.84–1.67)
						Lung female	0.85 (0.53–1.35)
Cui,2008 [37]	USA; Case control (population based)	558/837	-	Epicatechin	≥9 VS <3 mg/d	Lung	0.66 (0.46–0.94)	age, sex, race-ethnicity, years of schooling, smoking status, pack-years of tobacco smoking, and daily energy intake
						Lung smokers	0.61 (0.40–0.93)
						Lung nonsmokers	0.81 (0.40–1.60)
				Catechin	≥3 VS <1 mg/d	Lung	0.54 (0.38–0.76)
						Lung smokers	0.44 (0.29–0.66)
						Lung nonsmokers	0.77 (0.39–1.50)
Cutler,2008 [94]	USA; Cohort	All cancer 7,534, lung cancer 849 / 34,708	19	Flavan-3-ols	134.8–1051.6 VS <0.001–6.7 mg/d	Any cancer combined	0.97 (0.90–1.05)	age, energy, education level, race, BMI, multivitamin use, smoking history and pack years, activity level
						Lung smokers	1.07 (0.85–1.36)
						Lung nonsmokers	1.04 (0.54–2.02)
Lagiou,2004 b [95]	Greece; Case control (hospital based)	154/145	-	Flavan-3-ols	Per 1 s.d. increment	Lung	1.02 (0.70–1.49)	age, total energy intake, smoking status, pack-years, fruit and vegetable consumption
Rossi,2008 [96]	Italy; Case control (hospital based)	1,031/ 2,411	-	Flavan-3-ols	>77 VS <16.3 mg/d	Ovary	0.89 (0.67–1.17)	age, study center, education, year of interview, parity, oral contraceptive use and family history of ovarian or breast cancer or both in first-degree relatives
Arem,2013 [97]	USA; Cohort	2,379/537,104	10.6	Flavan-3-ols	331.2 VS 8.6 mg/d	Pancreas	1.03 (0.91–1.17)	sex, smoking, diabetes, BMI, alcohol, calories, saturated fat and red meat intake, with age as the underlying time metric
Bobe,2008 [39]	Finland; Cohort	306/27,111	16.1	Flavan-3-ols	>9.75 VS ≤0.90 mg/d	Pancreas	0.92 (0.64-1.31)	age, smoking, total number of cigarettes per day, self-reported history of diabetes mellitus, and energy-adjusted saturated fat intake
Rossi,2012 [98]	Italy; Case control (hospital based)	326/652	-	Flavanols	>97.7 VS ≤23.8 mg/d	Pancreas	0.63 (0.38–1.03)	gender, age, center of study, year of interview, education, history of diabetes, smoking, alcohol drinking and non-alcohol energy intake
Bosetti,2006 [99]	Italy; Case control (hospital based)	1,294/1,451	-	Flavan-3-ols	≥102.1 VS <29.9 mg/d	Prostate	1.30 (1.01–1.69)	age, study center, education, BMI, family history of prostate cancer and total calorie intake.
Geybels, 2013 [38]	Netherlands; Cohort	3,362/58,279	18	Total catechin: ((+)-catechin; (−)-epicatechin; (+)-gallocatechin; (−)-epigallocatechin; (−)-epicatechin gallate; (−)-epigallocatechin gallate)	98.7 VS 14.5 mg/d	Prostate	0.97 (0.82-1.15)	age, flavonoid intake, family history of prostate cancer, smoking, nonoccupational physical activity, BMI, height, diabetes, education and intake of energy, alcohol, calcium, lycopene, vitamin E, red meat and coffee
Wang,2014 b [100]	USA; Cohort	3,974/43,268	7.8	Flavan-3-ols	≥73.9 VS <10.4 mg/d	Prostate	1.18 (1.06-1.30)	age, race, family history of prostate cancer, BMI in 1999, smoking status, aspirin use, total energy intake, history of prostate-specific antigen screening, and diabetes
Bosetti,2007 [101]	Italy; Case control (hospital based)	767/1,534	-	Flavan-3-ols	≥90.6 VS <21.3 mg/d	Kidney	0.77 (0.56-1.06)	sex, age, study center, period of interview, education, smoking, alcohol drinking, BMI, occupational physical activity, family history of kidney cancer, and total energy intake
Xiao,2014 [102]	USA; Cohort	586/491,840	9	Flavan-3-ols	161.89–7205.21 VS 0.00–17.16 mg/d	Thyroid	0.66 (0.51, 0.85)	sex, total caloric intake, smoking status, education level, alcohol intake, race, BMI, family history of cancer
Rossi,2013 [103]	Italy; Case control (hospital based) control (hospital based)	454/908	-	Flavanols	IV vs I–III quartile category	Uterus	0.99 (0.74–1.32)	age, year of interview, education, BMI, history of diabetes, age at menarche, menopausal status/age at menopausal status, parity, oral contraceptive use, and hormone-replacement therapy use