Consumption of red and processed meat and esophageal cancer risk: Meta-analysis

Table 1 Characteristics of the studies included in the meta analysis

Ref.	Study period	Sex	No. of cases	No. cohorts or controls	Dietary assessment	Exposure and comparison level	Adjusted RR (95%CI)	Study quality1	Adjustment for confounders
Cohort studies
Keszei et al[11]	1986-2002	M	ESCC: 107	120 852	FFQ 150 items	Red meat		9	Age, smoking (including years and numbers per day), total energy, BMI, alcohol drinking, vegetable, fruit, education, non-occupational PA
		F	EAC: 145			ESCC
		M				Q5 vs Q1	2.66 (0.94-7.48)
		F				T3 vs T1	0.87 (0.42-1.79)
						EAC
		M				Q5 vs Q1	0.57 (0.28-1.19)
		F				T3 vs T1	1.09 (0.44-2.75)
						Processed meat
						ESCC
		M				Q5 vs Q1	3.47 (1.21-9.94)
		F				T3 vs T1	0.63 (0.28-1.44)
						EAC
		M				Q5 vs Q1	0.94 (0.46-1.89)
		F				T3 vs T1	0.58 (0.22-1.50)
Cross et al[12]	1995-2006	C	ESCC: 215	494 979	FFQ 124 items	Red meat (Q5 vs Q1)		9	Age, sex, BMI, education, ethnicity, smoking, alcohol drinking, PA at work, vigorous PA, daily intakes of fruit, vegetable, saturated fat, energy
			EAC: 630			ESCC	1.79 (1.07-3.01)
						EAC	1.15 (0.84-1.57)
						Processed meat (Q5 vs Q1)
						ESCC	1.32 (0.83-2.10)
						EAC	1.08 (0.81-1.43)
González et al[13]	1992-1998	C	EAC: 65	521 457	FFQ 88-266 items	Red meat (T3 vs T1)	1.67 (0.75-3.72)	8	Sex, height, weight, education, smoking, smoking intensity, work and leisure PA, intakes of alcohol, energy, vegetable, citrus fruit, non-citrus fruit, types of meat intake were mutually adjusted
						Processed meat (T3 vs T1)	3.54 (1.57-7.99)
Yu et al[14]	1974-1989	C	All: 1162	12 693	Questionnaire 15 items	Pork (never vs regular/occasional)	1.37 (1.11-1.68)	7	Age, sex
Case-control studies
Ward et al[15]	1988-1993	C	EAC: 124	449	Questionnaire 100 items	Red meat (> 157.2 g/d vs ≤ 73.8 g/d)	2.85 (1.00-8.16)	5	Age, sex, race, vital status, year of birth, sex, No. of cigarettes per day, BMI, intakes of retinoic acid, folate, riboflavin, zinc, carbohydrate, protein, total energy.
						Processed meat (> 52.3 g/d vs ≤ 16.1 g/d)	1.40 (0.62-3.15)
De Stefani et al[16]	1996-2004	C	ESCC: 234	2020	FFQ 64 items	Red meat ( T3 vs T1)	4.97 (2.98-8.29)	7	Age, sex, residence, education, BMI, smoking, drinking, mate temperature, total energy, total intakes of vegetable and fruit, scored pattern
						Processed meat (T3 vs T1)	0.76 (0.51-1.13)
Gao et al[17]	1997-2005	C	ESCC: 600	1514	Questionnaire 35 items	Red meat (> weekly vs monthly/seldom/never)	1.37 (1.03-1.82)	5	Age, sex, geographic region
Wu et al[18]	2003-2007	C	All: 1495	3819	FFQ	Red meat (Q4 vs Q1)	1.13 (0.94-1.36)	7	Age, sex, education, previous income, BMI, pack-years smoking, weekly ethanol intake, study area
Hajizadeh et al[19]	N/A	C	ESCC: 47	96	FFQ168 items	Red meat (T3 vs T1)	2.47 (0.76-7.96)	6	Age, sex, education, tobacco smoking, symptomatic gastroesophageal reflux, BMI, total energy
						Processed meat (T3 vs T1)	1.10 (0.36-2.47)
O'Doherty et al[20]	2002-2005	C	EAC: 221	256	FFQ101 items	Red meat (Q4 vs Q1)	3.15 (1.38-7.20)	7	Age, sex, smoking, BMI 5 yr before interview date, education, job type, Intakes of energy, fruit, vegetable, alcohol (g/d), Helicobacter pylori infection, nonsteroidal anti-inflammatory drug use 5 yr before, interview date, gastroesophageal reflux symptoms, location, types of meat intake were mutually adjusted
						Processed meat (Q4 vs Q1)	1.41 (0.67-2.95)
Sapkota et al[21]	1999-2003	C	ESCC: 187	1110	Questionnaire 23 items	Red meat (≥ 1/wk vs < 1/mo)	0.62 (0.19-2.09)	6	Age, sex, country, tobacco pack-year, education, BMI, frequency of alcohol consumption, vegetable, fruit consumption
						Processed meat (≥ 1 time/wk vs < 1 time/mo)	1.12 (0.52-2.41)
Navarro Silvera et al[22]	1993-1995	C	EAC: 282	687	FFQ104 items	Red meat (high vs low)	3.02 (1.65-5.52)	7	Age, sex, study site, race, proxy status, income, education, BMI, No. of smoking cigarettes per day, intakes of beer, wine, liquor, and energy
Wang et al[23]	2004-2006	M	ESCC: 355	408	Questionnaire	Pork (often vs none/seldom)	2.06 (1.42-2.99)	5	Age, sex, marital status, education
		F					1.91 (1.16-3.16)
Wu et al[24]	1992-1997	C	EAC: 206	1308	Questionnaire 124 items	Red meat (Q4 vs Q1)	1.29 (0.8-2.2)	5	Age, sex, race, birthplace, education, smoking, BMI, reflux, use of vitamins, total energy
						Processed meat (Q4 vs Q1)	1.23 (0.7-2.1)
Chen et al[25]	1988-1993	C	EAC: 124	449	Questionnaire54 items	Red meat (Q4 vs Q1)	1.4 (0.61-3.2)	7	Age, sex, energy intake, respondent type, BMI, alcohol drinking, smoking, education, family history, vitamin supplement use, age squared for EAC
						Processed meat (Q4 vs Q1)	1.7 (0.71-3.9)
Takezaki et al[26]	1988-1997	M	All: 284	11 888	Questionnaire	Beef (≥ 3/wk vs ≤ 3/mo)	0.9 (0.6-1.5)	5	Age, year and season of visit, smoking, drinking
Bosetti et al[27]	1992-1997	C	ESCC:304	743	FFQ78 items	Red meat (Q5 vs Q1)	1.93 (1.09-3.41)	5	Age, sex, area of residence, education, tobacco smoking, alcohol drinking, non-alcohol energy
Rolón et al[28]	1988-1991	C	All: 131	379	FFQ	Red meat (highest vs lowest)	3.8 (1.3-11.0)	5	Age, sex, alcohol, smoking, design variable of the study, hospital group, intakes of red meats, fats, fish, milk
Castelletto et al[29]	1986-1989	C	ESCC: 131	261	FFQ10 food groups	Beef (≥ daily vs < daily)	0.6 (0.3-0.9)	6	Age, sex, design variable, hospital, education, No. of cigarettes smoking per day, intakes of alcohol, barbecued meat, potatoes, raw vegetables, cooked vegetables
Tavani et al[30]	1984-1992	C	All: 46	230	FFQ14 items	Ham (Q3 vs Q1)	1.4 (0.6-3.3)	5.5	Age, sex, education, total alcohol intake
						Liver (Q2 vs Q1)	1.1 (0.5-2.3)
Rogers et al[31]	1983-1987	C	All: 127	466	FFQ125 items	Beef (≥ 1/wk vs < 1/wk)		5	Age, sex, pack-years of cigarette, drink-years of alcohol, energy intake, beta-carotene intake, ascorbic acid intake
						As a main dish	0.8 (0.4-1.4)
						As a sandwich	1.0 (0.6-1.7)
						Pork (≥ 1/wk vs < 1/wk)	1.2 (0.8-2.5)
Yu et al[32]	1975-1981	C	Beef: 267	Beef: 267	Questionnaire10 food groups	Beef (≥ 5/wk vs ≤ 1/wk)	1.3 (0.6-2.7)	5	Age, sex, race
			Fried bacon or ham: 265	Fried bacon or ham: 265		Fried bacon or ham ( ≤ 1/wk vs≥ 5/wk )	2.0 (1.1-3.5)
			Barbecued or smoked meat: 268	Barbecued or smoked meat: 268		Barbecued or smoked meat (≥ 2/wk vs ≤ 1/wk)	1.7 (0.9-3.0)
Chen et al[33]	1996-2005	M	ESCC: 320	709	Questionnaire6 items	Cured meat (≥ 1/wk vs < 1/wk )	0.8 (0.4-1.4)	5	Age, educational level, ethnicity, source of hospital, smoking, alcohol drinking, areca nut chewing
Yang et al[34]	2003-2004	C	All: 185	185	Questionnaire 9 Items	Processed meat (> 3 meals/wk vs < 1 meal/wk)	0.66 (0.31-1.41)	5.5	Family history of esophageal cancer, occupation, smoking, drinking, eating hot food, eating speed, intakes of vegetables, fruit, pickled vegetables, fresh meat, egg, tea, water supply
Levi et al[35]	1992-2002	C	All:138	660	FFQ79 items	Processed meat(> 3.2 freq/wk vs < 0.8 freq/wk)	4.48 (2.05-9.79)	6	Age, sex, education, smoking, intakes of alcohol, energy, fruit and vegetable intake
Li et al[36]	1997-2000	C	All:1248	1248	Questionnaire 12 items	Sowbelly (daily vs < 1/wk)	2.28 (1.6-3.3)	5	Age, sex, income, residence, occupation, alcohol, tobacco
Takezaki et al[37]	1995-2000	C	All: 199	333	Questionnaire19 items	Salted meat (≥ 1/wk vs < 1/mo)	0.93 (0.38-2.29)	6	Age, sex, smoking, drinking

¹Study quality was assessed using the Newcastle-Ottawa Scale (range: 1-9 stars). RR: Relative risk; M: Male; F: Female; C: Combined males and females; ESCC: Esophageal squamous cell carcinoma; EAC: Esophageal adenocarcinoma; FFQ: Food frequency questionnaire; BMI: Body mass index; PA: Physical activity; N/A: Not available.

Table 2 Combined relative risks and 95%CI for esophageal cancer associated with red meat or processed meat by other factors in both cohort and case-control studies

	Red meat				Processed meat
Factors	Studies (n)	Ref.	RR (95%CI)	P for heterogeneity	Studies (n)	Ref.	RR (95%CI)	P for heterogeneity
Histological subtypes
EAC	9	[11-13,15,20,22,24,25,32]	1.42 (1.02-1.98)	0.19	8	[11-13,15,20,24,25,32]	1.38 (1.07-1.78)	0.3
ESCC	9	[11,12,16,17,19,21,23,27,29]	1.55 (1.10-2.17)		7	[11,12,16,19,21,27,33]	1.08 (0.80-1.44)
Study location
Asia	6	[14,17,18,19,23,26]	1.33 (1.09-1.62)	0.67	5	[19,33,34,36,37]	1.09 (0.61-1.95)	0.65
Europe	6	[11,13,20,21,27,30]	1.33 (0.86-2.07)		7	[11,13,20,21,27,30,35]	1.49 (0.99-2.23)
United States	7	[12,15,22,24,25,31,32]	1.32 (1.03-1.70)		5	[12,15,21,25,32]	1.30 (1.08-1.57)
South America	3	[16,28,29]	2.20 (0.48-10.04)		1	[16]	0.76 (0.51-1.13)
Sex
Male	3	[11,23,26]	1.26 (0.66-2.41)	0.88	2	[11,33]	1.24 (0.58-2.65)	0.14
Female	2	[11,23]	1.31 (0.78-2.21)		1	[11]	0.61 (0.33-1.13)
Both	19	[12-22,24,25,27-32]	1.42 (1.17-1.71)		16	[12,13,15,16,19-21,24,25,27,30,32,34-37]	1.43 (1.15-1.77)
Study quality1
≥ 7	8	[11-14,16,18,20,22]	1.60 (1.20-2.13)	0.23	6	[11-13,16,20,25]	1.20 (0.88-1.62)	0.42
< 7	14	[15,17,19,21,23-32]	1.25 (1.02-1.54)		12	[15,19,21,24,27,30,32-37]	1.43 (1.11-1.86)

¹Study quality was assessed using the Newcastle-Ottawa Scale (range, 1-9 stars); RR: Relative risk; ESCC: Esophageal squamous cell carcinoma; EAC: Esophageal adenocarcinoma.