Red Meat and Processed Meat Volume 114

Red Meat and Processed Meat volume 114

This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 6–13 October 2015

LYON, FRANCE - 2018 iarc monographs oN the evaluation of carcinogenic risks to humans Red meat and processed meat

2.3 Cancer of the stomach and China, positive associations were reported in two studies: the EPIC cohort, which followed up The Working Group focused their review 521 457 participants (González et al., 2006), and on studies that clearly defined red meat or a case–control study of 226 gastric non-cardia processed meat (see Section 1 and Section 2.1). cancer (GNCA) cases and 451 controls nested Studies were excluded if: (1) risk estimates were within the Shanghai Men’s Health Study (SMHS) presented for total meat (red and processed meat cohort (Epplein et al., 2014). [The Working combined) intake; (2) the type of meat was not Group noted that the strengths of the EPIC defined or included white meat; (3) fewer than study (González et al., 2006) were its large size 100 cases were reported, due to the limited statis- and analysis by subsite, histological type, and tical power, as a large database of high-quality H. pylori infection. For the study nested within studies were available; (4) a more recent report the Shanghai cohort (Epplein et al., 2014), the from the same study was available; (5) risk esti- Working Group noted that this population had mates, adjusted for important confounders, were over 90% prevalence of CagA-positive H. pylori not available (crude estimates were not consid- infection. In addition, socioeconomic status (or ered to be informative); (6) dietary patterns were education) was not included as a covariate, and the focus; and (7) outcomes were assessed using the items included in red meat were not detailed.] mortality data. Several other studies reported no association, Several cohort and case–control studies, or relative risks greater than one, but with wide conducted in areas all over the world, have confidence intervals that included the null value, reported on the association between red and between red meat consumption and gastric processed meat intake and cancer of the stomach. cancer. These studies included a cohort of 13 250 Important confounders for the assessment of this people older than 15 years from the Fukuoka association are age, tobacco smoking, socioeco- Prefecture in Japan (Ngoan et al., 2002); a popu- nomic status (or education), and energy intake. lation-based cohort of 61 433 Swedish women Infection with Helicobacter pylori is a risk factor (Larsson et al., 2006); the Japan Collaborative for cancer of the stomach, although its role in the Cohort Study for Evaluation of Cancer (JACC association between intake of red or processed Study), which included 42 513 men and 57 777 meat and cancer of the stomach is unclear. Salt women (Iso et al., 2007); the NIH-AARP study intake may also be a confounder, as there is cohort of 494 979 individuals Cross et al. (2011); evidence that it increases the risk of cancer of and a cohort of 120 852 men and women in the the stomach, and it is also present in preserved NLCS (Keszei et al., 2012). [The Working Group or salted (processed) meat; however, it is diffi- noted that processed meat was included in the cult to distinguish the effect of salt from that of definition of red meat in the NIH-AARP study.] preserved meat. (b) Processed meat 2.3.1 Cohort studies See Table 2.3.2 (a) Red meat Studies investigating the association between consumption of total processed meat, specific See Table 2.3.1 (web only; available at: http:// processed meat are presented below. Of the publications.iarc.fr/564) reviewed papers, we excluded papers reporting Of the publications on cohort studies that fewer than 100 cases (e.g. Kneller et al., 1991; Knekt reported on the association between red meat et al., 1999; Khan et al., 2004). Studies focusing and gastric cancer in the USA, Europe, Japan, on dietary pattern (e.g. Pham et al., 2010), studies

249 IARC MONOGRAPHS – 114 from mortality data (e.g. McCullough et al., 2001, appear to modify the association. [The Working Ngoan et al.., 2002; Tokui et al., 2005; Iso et al., Group noted that it was defined that white meat 2007), studies that were overlapping or updated was not included. The population size was large, (Cross et al., 2007) were excluded. Finally, seven and detailed information on subsite, histological studies were included. type, and H. pylori was available.] Among 7990 American men of Japanese In a population-based cohort of 61 433 ancestry in a cohort study in which 150 cases Swedish women, Larsson et al. (2006) found a of gastric cancer were observed, Nomura et al. positive association between long-term processed (1990) reported an age-adjusted relative risk of meat consumption (using two surveys 10 years 1.3 (95% CI, 0.9–2.0) for the highest versus the apart) and gastric cancer risk. During 18 years lowest frequency of intake of ham and sausage. of follow-up, 156 incident cases of gastric cancer [The Working Group noted that only age was were diagnosed. The multivariate-adjusted adjusted. Smoking status was related to gastric hazard ratio for the highest versus the lowest cancer, but was not adjusted for. No subsite ana- serving per week of total processed meat was lysis was conducted.] 1.66 (95% CI, 1.13–2.45; 67 exposed cases). [The In a cohort of 11 907 randomly selected Working Group noted that using a survey from Japanese residents of Hawaii, USA, with an two time points enabled the effect of long-term average follow-up period of 14.8 years, 108 exposure to be seen. The number of cases was observed cases of gastric cancer (44 women, 64 small. No subsite analysis was conducted.] men) were identified, and no association was In the NIH-American Association of Retired observed between processed meat consumption Persons (NIH-AARP Diet and Health Study and incidence of gastric cancer (Galanis et al., cohort of 494 979 individuals, aged 50–71 1998). The adjusted odds ratios for the highest years, Cross et al. (2011) investigated intake of frequency compared with the lowest frequency processed meat and meat cooking by-products of consumption were 1.0 (95% CI, 0.5–1.9; 20 with accrued 454 gastric cardia cancers (GCAs) exposed cases) and 1.2 (95% CI, 0.6–2.4; 15 and 501 GNCAs. After adjusting for impor- exposed cases) for men and women, respectively. tant confounders, no association was observed [The Working Group noted that the case number between processed meat consumption and was small, especially for women. An FFQ was GCA and GNCA. For the highest versus the used with only 13 items. No subsite analysis was lowest quintile, the hazard ratios were 0.82 (95% conducted.] CI, 0.59–1.14; Ptrend = 0.285) and 1.09 (95% CI,

González et al. (2006) examined the asso- 0.81–1.48; Ptrend = 0.329), respectively. Nitrate and ciation between processed meat consumption nitrite were not associated with gastric cancer. and risk of gastric cancer in the EPIC study. The [The Working Group noted that this was a large adjusted hazard ratio for the association with study with a large number of cases, both for GCA processed meat intake (highest vs lowest quin- and GNCA.] tile) was 1.62 (95% CI, 1.08–2.41; Ptrend = 0.02), In the Netherlands Cohort Study (NLCS), which was more apparent in non-cardia cancer Keszei et al. (2012) reported on the associa-

(HR, 1.92; 95% CI, 1.11–3.33; Ptrend = 0.01) than tion between intake of processed meat and in cardia cancer (HR, 1.14; 95% CI, 0.52–2.49; gastric cancer risk in both men and women,

Ptrend = 0.91). No difference was seen by histolo- after adjusting for important confounders. The gical type. When H. pylori infection was consid- case–cohort study consisted of 120 852 men and ered in the case–control data set nested in the women, and after 16.3 years of follow-up, 163 present study, H. pylori antibody status did not GCAs and 489 GNCAs were observed. The

250 Red meat and processed meat definition of processed meat included all meat et al., 2001; Chen et al., 2002; Huang et al., 2004; items that had undergone some form of preser- Lissowska et al., 2004; Wu et al., 2007; Hu et al., vation, including cold cuts, croquettes, and all 2008; Navarro Silvera et al., 2008; Pourfarzi et al., types of sausages. For the highest compared with 2009; Gao et al., 2011; Wang et al., 2012, 2014; the lowest category, the relative risks of intake Ward et al., 2012; Zamani et al., 2013). Although of processed meat for GCA and GNCA were odds ratios greater than one were reported in all

1.49 (95% CI, 0.81–2.75; Ptrend = 0.34; 32 exposed but three studies (Kono et al., 1988; Ji et al., 1998; cases) and 1.19 (95% CI, 0.78–1.79; Ptrend = 0.36; Huang et al., 2004), the studies had several meth- 77 exposed cases), respectively, in men. [The odological limitations, including low precision Working Group noted that the number of cases power resulting from a small number of cases, for gastric cancer of the cardia was small. A use of an FFQ that may not have been validated, detailed FFQ with 150 items was used.] lack of adjustment for important confounders Epplein et al. (2014) investigated the interac- (e.g. smoking, total energy intake), inclusion of tion between preserved meat, comprising intake processed meat in the definition of red meat, of smoked meat, salted meat, and “Chinese” and issues with the selection of hospital-based sausage, and H. pylori infection among 226 controls. Few studies reported analyses by GNCA cases and 451 controls nested within the subsite. The Working Group put more emphasis Shanghai Men’s Health Study (SMHS prospec- on two well-designed population-based case– tive cohort. Overall, after adjusting for important control studies from the USA (Wu et al., 2007) confounders, including age, education, smoking, and Canada (Hu et al., 2008) that used validated and total energy, preserved meat intake was not FFQs and adjusted for important confounders. associated with gastric cancer. For the highest compared with the lowest category of intake, the (b) Processed meat relative risk of preserved meat was 1.01 (95% CI, The Working Group reviewed several case–

0.66–1.55; Ptrend = 0.99). An effect modification by control studies of gastric cancer that reported on

H. pylori was not apparent (Pinteraction = 0.09). [The the association with consumption of processed Working Group noted that information on H. meat. Few studies were hospital-based (Lee et al., pylori infection was available. This was a study in 1990; Boeing et al., 1991b; De Stefani et al., 1998, a population with over 90% prevalence of CagA- 2012; Huang et al., 2004), and the majority were positive H. pylori infection. Socioeconomic status population-based (Risch et al., 1985; La Vecchia or education was not adjusted for. Processed meat et al., 1987; Sanchez-Diez et al., 1992; Ward & intake was low in the study population.] López-Carrillo, 1999; Palli et al., 2001; Takezaki et al., 2001; Chen et al., 2002; Nomura et al., 2003; 2.3.2 Case–control studies Lissowska et al., 2004; Wu et al., 2007; Navarro Silvera et al., 2008; Pourfarzi et al., 2009; Hu (a) Red meat et al., 2011; Ward et al., 2012). See Table 2.3.3 (web only; available at: http:// (i) Hospital-based case–control studies publications.iarc.fr/564) The Working Group reviewed 20 reports from See Table 2.3.4 case–control studies of gastric cancer reporting Several hospital-based case–control studies of on the association with consumption of red meat gastric cancer were conducted in Taipei, Taiwan, (La Vecchia et al., 1987; Kono et al., 1988; Ward China (Lee et al., 1990), Germany (Boeing et al., et al., 1997; De Stefani et al., 1998; Ji et al., 1998; 1991a, b), Uruguay (De Stefani et al., 1998, 2012), Tavani et al., 2000; Palli et al., 2001; Takezaki and Japan (Huang et al., 2004). All but two

251 IARC MONOGRAPHS – 114 studies (Huang et al., 2004; De Stefani et al., exposed cases). Although, in a previous study, 1998) reported increased risks of gastric cancer Ward et al. (1997) reported a positive association associated with processed meat consumption in between processed meat and gastric cancer based multivariable models. The possibility of selec- on servings per day (Ptrend = 0.06). The 2012 publi- tion bias (due to the selection of hospital-based cation conducted a more accurate analysis, esti- controls that may have been admitted for condi- mating grams per day and considering adequate tions leading to modifications in diet), recall bias, confounding factors. [The Working Group noted and confounding (due to inadequate adjustment that the response rate was high. No subsite ana- for potential confounding variables) could not be lysis was conducted.] ruled out. (ii) Population-based case–control studies 2.3.3 Meta-analyses See Table 2.3.5 (a) Red meat Several population-based case–control Among the meta-analyses published on studies of gastric cancer that reported on gastric cancer and meat consumption, Song processed meat consumption were identi- et al. (2014) was the most recent and compre- fied from Canada Risch( et al., 1985; Hu et al., hensive, including 18 studies (4 cohort studies, 2011), Italy (La Vecchia et al., 1987; Palli et al., 14 case–control studies) and 1 228 327 subjects, 2001), Poland (Boeing et al., 1991a; Lissowska published between 1997 and 2013. Two case– et al., 2004), Spain (Sanchez-Diez et al., 1992), control studies, Wang et al. (2012) and Navarro Mexico (Ward & López-Carrillo, 1999), China Silvera et al. (2008) were not included in the (Takezaki et al., 2001), the Islamic Republic of meta-analysis. [Therefore, the Working Group Iran (Pourfarzi et al., 2009), and the USA, specif- did not place great weight on the meta-analysis.] ically Nebraska (Chen et al., 2002; Ward et al., In the meta-analysis, high–red meat intake was 1997, 2012), Hawaii (Nomura et al., 2003), Los found to be associated with an increased risk Angeles (Wu et al., 2007), Connecticut, New of gastric cancer. The summary relative risk of Jersey, and western Washington state (Navarro gastric cancer for the highest compared with the Silvera et al., 2008). lowest categories was 1.37 (95% CI, 1.18–1.59; Nearly all the studies reported odds 2 Pheterogeneity < 0.001; I = 67.6%). A significant asso- ratios above one, although chance, bias, and ciation was also observed with population-based confounding could not be ruled out as possible case–control studies (RR, 1.58; 95% CI, 1.22–2.06; explanations for the observed excesses due to 2 Pheterogeneity < 0.001; I = 73.0%) and hospi- study limitations, including inadequate adjust- tal-based case–control studies (RR, 1.63; 95% CI, ment for potential confounders (e.g. tobacco 2 1.38–1.92; Pheterogeneity = 0.284; I = 19.1%), but not smoking, total energy intake), recall bias, and with cohort studies (RR, 1.00; 95% CI, 0.83–1.20; information bias (e.g. large amount of informa- 2 Pheterogeneity = 0.158; I = 33.9%). A significant asso- tion obtained from proxy respondents). ciation was also shown in the subgroup analysis However, no association between processed by geographical area (Asia, Europe), publication meat and gastric cancer was reported in a popu- year (≥ 2000), sample size (< 1000, ≥ 1000), and lation-based case–control study from 1988 to study quality score. The dose–response analysis 1994 in Nebraska, USA (Ward et al., 2012): the revealed that gastric cancer was associated with a multivariate odds ratio for the highest versus 17% increased risk per 100 g/day increment of red the lowest quartile of processed meat consump- meat intake (RR, 1.17; 95% CI, 1.05–1.32). [The tion was 0.97 (95% CI, 0.51–1.85; Ptrend = 0.87; 46 Working Group noted that the dose–response

252 Red meat and processed meat analysis did not distinguish between cohort and case–control studies.] (b) Processed meat The most recent and comprehensive meta-analysis on the association between processed meat and gastric cancer was reported by Larsson et al. (2006). The meta-analysis included seven prospective cohort studies and 14 case–control studies. The summary relative risks of gastric cancer for the highest compared with the lowest categories of red meat intake were 1.24 (95% CI, 0.98–1.56; Pheterogeneity = 0.04) for cohort studies and 1.63 (95% CI, 1.31–2.01;

Pheterogeneity = 0.06) for case–control studies. In an exposure–response analysis, the meta-relative risks for gastric cancer were 1.15 (95% CI, 1.04–1.27) for cohort studies and 1.38 (95% CI, 1.19–1.60) for case–control studies per 30 g/day increment of processed meat intake. An elevated risk was also observed for the highest compared with the lowest categories of intake of specific items of processed meat. For bacon, the relative risks were 1.38 (1.12–1.71) for cohort studies and 1.37 (1.06–1.78) for case–control studies, and for sausage, the relative risks were 1.26 (0.92–1.72) for cohort studies and 1.49 (1.09–2.03) for case– control studies. [The Working Group noted that one case–control study in Paraguay (Rolón et al., 1995) was not included. Specific items of processed meat such as ham, bacon, or sausage were analysed separately from processed meat.]

253 IARC MONOGRAPHS – 114 Covariates controlled Age Age, years of education, Japanese place of birth, sex Age, years of education, Japanese place of birth, cigarette smoking, alcohol intake status Age, years of education, Japanese place of birth

Risk estimate (95% CI) 1.0 1.0 (0.7–1.4) 1.3 (0.9–2.0) 1.0 (0.6–1.4) 0.9 1.0 (0.6–1.7) 1.0 1.1 (0.6–2.0) 1.0 (0.5–1.9) 1.0 (0.3–1.4) 0.7 1.2 (0.6–2.4) Exposed cases/ Exposed cases/ deaths 71 43 36 34 39 35 18 26 20 16 13 15

: value: 0.37 value: 0.58 0.77 value: P P P

: Exposure category or level Risk by frequency for ham, bacon, and sausage ≤ 1 time/wk 2–4 times/wk ≥ 5 times/wk Risk by frequency for processed meats Men and women None 1–2 times/wk ≥ 3 times/wk Trend-test Risk by frequency for processed meats Men None 1–2 times/wk ≥ 3 times/wk Trend-test Risk by frequency for processed meats Women None 1–2 times/wk ≥ 3 times/wk Trend-test Organ site Stomach Stomach Stomach Stomach

Population size, description, exposure assessment method 7990; men of Japanese ancestry, born between residing 1919–1990, on the Hawaiian island of Oahu method: assessment Exposure questionnaire; FFQ for food and 24-h dietary recall for nutrients men, 6297 women); 11 907 (5610 Japanese selected randomly residents of Hawaii method: assessment Exposure questionnaire; FFQ

(1990) (1998)

et al. et al. Table 2.3.2 CohortTable studies on consumption of processed meat and cancer of the stomach Reference, location, enrolment/follow-up period, study design Nomura Hawaii, USA 1965–October 1986 Cohort study Galanis Hawaii, USA (Japanese residents) 1975–1994 Cohort study

254 Red meat and processed meat Covariates controlled Centre and age at EPIC study entry, and adjusted by sex, height, weight, education level, tobacco smoking, cigarette smoking intensity, work and leisure physical activity, alcohol intake, energy intake, vegetable intake, citrus fruit intake, and non- citrus fruit intake; red meat, poultry, processed and meat intakes were mutually adjusted

Risk estimate (95% CI) 1.00 1.10 (0.76–1.58) 1.16 (0.79–1.69) 1.62 (1.08–2.41) 1.18 (0.97–1.43) 1.64 (1.07–2.51) 1.00 1.19 (0.61–2.34) 1.04 (0.51–2.12) 1.14 (0.52–2.49) (0.59–1.34) 0.89 (0.29–1.96) 0.76 1.00 1.02 (0.60–1.71) 1.02 (0.59–1.77) 1.92 (1.11–3.33) 1.36 (1.06–1.74) 2.45 (1.43–4.21) Exposed cases/ Exposed cases/ deaths NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR

value: 0.02 value: value: 0.91 0.01 value: P P P

Exposure category or level meat Processed (quartiles) Q1 Q2 Q3 Q4 Continuous, observed Continuous, calibrated Trend-test meat(quartiles) Processed Q1 Q2 Q3 Q4 Continuous, observed Continuous, calibrated Trend-test meat Processed (quartiles) Q1 Q2 Q3 Q4 Continuous, observed Continuous, calibrated Trend-test Organ site Stomach Stomach/cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma

Population size, description, exposure assessment method aged yr, 35–70 usually521 457; from the general population method: assessment Exposure questionnaire; FFQ

(2006) et al.

Table 2.3.2 CohortTable studies on consumption of processed meat and cancer of the stomach Reference, location, enrolment/follow-up period, study design González European countries:Ten Denmark (Aarhus, Copenhagen), France, Germany (Heidelberg, Potsdam), Greece, Italy (Florence, Turin, Varese, Naples, Ragusa), the Netherlands (Bilthoven, Utrecht), Norway, Spain (Granada, Murcia, Asturias, Navarre, San Sebastián), Sweden (Malmö, Umeå), and the United Kingdom (Norfolk, Oxford) 1992–1999/2002 (depending on the study centre) Cohort study

255 IARC MONOGRAPHS – 114 Covariates controlled Age, education, BMI, energy, alcohol, fruits, vegetables

Risk estimate (95% CI) (0.05–4.01) 0.45 2.00 (1.06–3.79) 0.86 (0.03–27.0) (0.47–5.55) 1.62 0.002 (0.001–62.6) 2.67 (1.20–5.93) 1.00 1.46 (0.95–2.25) 1.66 (1.13–2.45) 1.00 1.27 (0.88–1.85) 1.55 (1.00–2.41) 1.00 1.44 (0.89–2.35) (0.93–2.41) 1.50 1.00 (0.65–1.51) 0.97 1.48 (0.99–2.22) Exposed cases/ Exposed cases/ deaths 40 201 22 47 12 113 51 38 67 52 66 38 24 55 77 45 46 65

value: 0.48 value: 0.42 value: 0.25 0.01 value: 0.05 value: value: 0.13 0.03 value: P P P P P P P antibody status: antibody status: antibody status: Exposure category or level Processed meat (nested case–control study) H. pylori Negative Positive Trend-test Processed meat (nested case–control study) H. pylori Negative Positive Trend-test Processed meat (nested case–control study) H. pylori Negative Positive Trend-test Processed (servings/wk) meat < 1.5 1.5–2.9 ≥ 3.0 Trend-test Bacon or side pork (servings/wk) 0 0.1–0.4 ≥ 0.5 Trend-test Sausage or hot dogs (servings/wk) < 0.4 0.4–0.9 ≥ 1.0 Trend-test Ham or salami (servings/wk) < 0.4 0.4–1.4 ≥ 1.5 Trend-test Organ site Stomach/ adenocarcinoma Stomach/cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma Stomach Stomach Stomach Stomach

Population size, description, exposure assessment method women and61 433; born in 1914 1948 method: assessment Exposure age-specific FFQ, questionnaire; portion sizes (mean of weighed and recorded food data random of 213 samples unpublished)

(2006) et al.

Table 2.3.2 CohortTable studies on consumption of processed meat and cancer of the stomach Reference, location, enrolment/follow-up period, study design González et al. (2006) (cont.) Larsson Uppsala and counties, Västmanland central Sweden Recruitment, 1987– 1990; end of follow-up, 2004 Cohort study

256 Red meat and processed meat Covariates controlled Age, sex, BMI, education, ethnicity, tobacco smoking, drinking, alcohol usual physical activity at work, vigorous physical activity, daily intake offruits, daily intake of vegetables, daily intake of saturated fat, daily intake of calories

Risk estimate (95% CI) 1.00 (0.64–1.24) 0.89 (0.66–1.26) 0.91 (0.67–1.28) 0.92 0.82 (0.59–1.14) 1.00 (0.92–1.09) 1.00 0.87 (0.64–1.18) 1.10 (0.82–1.47) 1.04 (0.77–1.41) 1.09 (0.81–1.48) 1.02 (0.94–1.11) Exposed cases/ Exposed cases/ deaths 68 78 93 108 107 NR 93 81 105 105 117 NR value: 0.285 value: 0.329 P P Exposure category or level Processed meat (quintile median, μg/1000 kcal) Q1 (1.7) Q2 (4.5) Q3 (7.8) Q4 (12.6) Q5 (23.2) All processed meats, continuous (per 10 g/1000 kcal) Trend-test Processed meat (quintile median, μg/1000 kcal) Q1 (1.7) Q2 (4.5) Q3 (7.8) Q4 (12.6) Q5 (23.2) All processed meats, continuous (per 10 g/1000 kcal) Trend-test Organ site Stomach/cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma Population size, description, exposure assessment method 494 979; men and women aged 50–71 yr; enrolled in 1995–1996. The following individuals were excluded: duplicates and participants who died or moved before the baseline questionnaire was received or withdrew from the study, who did not return the baseline questionnaire, whose baseline questionnaire was filled in by someone else on their behalf, who had prevalent cancer according to the cancer registry or self-report, and who had extreme daily total energy intake method: assessment Exposure questionnaire; dietary intake of various food items was assessed through a 124-item FFQ (usual frequency of consumption and portion size information of foods over the previous Portion 12 mo). sizes and daily nutrient intakes were calculated from the 1994–1996 USA Department of Agriculture‘s Continuing Survey of Food Intakes by Individuals. “Processed meat” was bacon, red meat sausage, poultry sausage, luncheon meats and (red white cold meat), cuts and (red white ham, meat), regular hot dogs, and low-fat hot dogs made from poultry; meat added to complex food mixtures, such as pizza, chilli, lasagne, and stew, contributed to the relevant meat type

(2011) et al. Table 2.3.2 CohortTable studies on consumption of processed meat and cancer of the stomach Reference, location, enrolment/follow-up period, study design Cross Florida, California, Louisiana, New Jersey, Carolina, North Pennsylvania, and two metropolitan areas (Atlanta, Georgia, and Detroit, Michigan), USA End of 2006 Cohort study

257 IARC MONOGRAPHS – 114 Covariates controlled Age, sex, BMI, education, ethnicity, tobacco smoking, drinking, alcohol usual physical activity at work, vigorous physical activity, daily intake offruits, daily intake of vegetables, daily intake of saturated fat, daily intake of calories

Risk estimate (95% CI) 1.00 1.17 (0.77–1.77) 0.64 (0.40–1.02) (0.61–1.45) 0.94 (0.52–1.25) 0.81 0.99 (0.90–1.09) 1.00 0.72 (0.47–1.11) 0.88 (0.58–1.32) (0.58–1.31) 0.87 (0.47–1.08) 0.71 0.89 (0.77–1.03) 1.00 (0.60–1.35) 0.90 (0.59–1.33) 0.89 (0.61–1.37) 0.91 1.04 (0.69–1.55) 1.01 (0.92–1.10) Exposed cases/ Exposed cases/ deaths 39 57 36 61 62 NR 44 40 55 61 55 NR 50 48 50 56 73 NR value: 0.259 value: 0.25 value: 0.578 P P P Exposure category or level Nitrate (quintile median, μg/1000 kcal) Q1 (24.9) Q2 (66.9) Q3 (112.7) Q4 (174.5 (298.0) Q5 All nitrates, continuous kcal) μg/1000 100 (per Trend-test Nitrite (quintile median, μg/1000 kcal) Q1 (12.1) Q2 (34.6) Q3 (61.4) Q4 (102.9) Q5 (199.2) All nitrites, continuous kcal) μg/1000 100 (per Trend-test Nitrate (quintile median, μg/1000 kcal) (24.2) Q1 Q2 (66.9) Q3 (112.7) Q4 (174.5) (298.0) Q5 All nitrates, continuous kcal) μg/1000 100 (per Trend-test Organ site Stomach/ stomach cardia adenocarcinoma Stomach/cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma Population size, description, exposure assessment method 303 156; men and women aged yr;5–71 enrolled in 1995–1996. The following individuals were excluded: duplicates and participants who died or moved before the risk factor questionnaire was received or withdrew from the study, who did not return the risk factor questionnaire, whose risk factor questionnaire was filled in by someone else on their behalf, who had prevalent cancer according to the cancer registry or self-report, and who had extreme daily total energy intake method: assessment Exposure questionnaire; dietary intake of various food items was assessed through a 124-item FFQ (usual frequency of consumption and portion size information of foods over the previous Portion 12 mo). sizes and daily nutrient intakes were calculated from the 1994-1996 USA Department of Agriculture’s Continuing Survey of Food Intakes by Individuals. A risk factor questionnaire sent 6 mo later elicited detailed information on meat intake and cooking preferences. Nitrate and nitrite intake from processed meat was estimated using a database of measured values from types 10 of processed meats, which represented 90% of processed meats consumed in the USA

258 Red meat and processed meat Covariates controlled Age, smoking status, years of cigarette smoking, number of cigarettes smoked per total day, energy intake, BMI, alcohol intake, vegetable intake), fruit intake, levels of education, non-occupational physical activity

Risk estimate (95% CI) 1.00 0.77 (0.51–1.15) 0.79 (0.53–1.18) 1.04 (0.71–1.52) (0.63–1.37) 0.93 1.02 (0.91–1.15) 1.00 1.51 (0.86–2.64) 0.89 (0.47–1.68) (0.71–2.24) 1.26 1.49 (0.81–2.75) 1.15 (0.71–1.86) 1.00 1.05 (0.71–1.56) (0.64–1.44) 0.96 1.09 (0.73–1.63) 1.19 (0.78–1.79) Exposed cases/ Exposed cases/ deaths 54 44 48 67 64 NR 23 34 21 29 32 139 62 65 59 66 77 value: 0.615 value: value: 0.34 value: 0.36 P P P

: : Exposure category or level Nitrite (quintile median, μg/1000 kcal) Q1 (12.1) Q2 (34.6) Q3 (61.4) Q4 (102.9) Q5 (199.2) All nitrite, continuous kcal) μg/1000 100 (per Trend-test Processed meat intake Men Q1 Q2 Q3 Q4 Q5 Continuous g/day (50 increment) Trend-test Processed meat intake (quintiles) Men Q1 Q2 Q3 Q4 Q5 Trend-test Organ site Stomach/ non-cardia adenocarcinoma Stomach/cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma

Population size, description, exposure assessment method 120 852 individuals were recruited, and finally,3923 sub-cohort members were used in the analysis (case–cohort design); the sample was selected from 204 municipal population registries throughout the Netherlands by sex-stratified random sampling method: assessment Exposure questionnaire; FFQ

(2012)

et al. Table 2.3.2 CohortTable studies on consumption of processed meat and cancer of the stomach Reference, location, enrolment/follow-up period, study design Cross et al. (2011) (cont.) Keszei TheNetherlands 1986–2002 Cohort study

259 IARC MONOGRAPHS – 114

H. pylori Covariates controlled Age, smoking, history gastritis, of regular aspirin use, total energy intake, high-risk infection

Risk estimate (95% CI) 1.00 1.19 (0.41–3.44) 1.12 (0.36–3.47) 0.70 (0.14–3.47) 1.00 1.21 (0.81–1.81) 1.11 (0.73–1.70) 1.00 1.13 (0.74–1.72) 1.01 (0.66–1.55) 1.00 0.96 (0.53–1.72) (0.41–1.51) 0.79 1.00 1.42 (0.80–2.52) (0.76–2.36) 1.34 Exposed cases/ Exposed cases/ deaths 7 8 9 24 51 56 53 71 81 74 37 29 20 34 52 54 proteins), tertiles proteins), value: 0.89 value: 0.7 value: 0.99 value: 0.49 0.09 value: H. pylori P P P P P proteins), tertiles proteins),

: : H. pylori Exposure category or level Processed meat intake Women T1 T2 T3 Continuous g/day (50 increment) Trend-test Processed meat intake (tertiles) Women T1 T2 T3 Trend-test Processed meat intake tertiles (times/mo), 0.20) (≤ T1 (0.21–1.42) T2 T3 (1.42) Trend-test Processed meat intake (times/mo) in risk low residents (0–4 seropositive results to 6 T1 T2 T3 Trend-test Processed meat intake (times/mo) in high risk residents (seropositive results to 6 T1 T2 T3 Trend-test Organ site Stomach/cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma

Population size, description, exposure assessment method Cases: 226 incident cases; permanent residents of urban Shanghai permanent residents Controls: 451; urbanof Shanghai method: assessment Exposure questionnaire; validated FFQ; frequency of intake and not amount; preserved meat was smoked meat, salted meat, and Chinese sausage

(2014)

et al. Table 2.3.2 CohortTable studies on consumption of processed meat and cancer of the stomach Reference, location, enrolment/follow-up period, study design Keszei et al. (2012) TheNetherlands 1986–2002 Cohort study (cont.) Epplein Shanghai, China Recruitment, 2002– 2009 2006; follow-up, case–control Nested study BMI, body mass index; CI, confidence interval; EPIC, European Prospective Investigation into Cancer Nutrition;and FFQ,food frequencyClassification questionnaire; of Diseases; h, hour; ICD, mo,International month; NR, not reported; wk,week; yearyr,

260 Red meat and processed meat Covariates controlled Adjusted for only risk factors significantly associated with stomach cancer in univariate analysis Adjusted for age, sex, hospital, raw vegetables, citrus fruit, cheese, wholemeal bread Risk estimate CI) (95% 1.00 1.24 2.90 1.00 1.26 3.26 1.00 1.61 1.72 1.00 2.04 2.31 1.00 1.48 3.18 1.00 (0.82–2.31) 1.37 2.21 (1.32–3.71) – Exposed cases/ deaths 129 50 31 137 55 18 31 156 23 23 146 41 266 105 49 NR NR NR NR for trend for = 9.46 2 Exposure category level or 2–5 meals/mo ≥ 6 meals/mo Salted meat consumption, between ages 20 and 39 2–5 meals/mo ≥ 6 meals/mo Cured meat consumption, before age 20 2–5 meals/mo ≥ 6 meals/mo Cured meat consumption, between ages 20 and 39 2–5 meals/mo ≥ 6 meals/mo Salted meat consumption (frequency/mo) 2–5 meals/mo ≥ 6 meals/mo Processed meat, tertile 1 (lowest) Processed meat, tertile 3 (highest) χ Salted meat consumption, before age 20 < 1 meal/mo < 1 meal/mo < 1 meal/mo < 1 meal/mo < 1 meal/mo Processed meat, tertile 2 Organ site Stomach Stomach

Population size, description, exposure assessment method Cases: the 143; local coordinators identified all patients younger than 80 yr with histologically confirmed incident stomach cancer admitted to hospitals, organized interviewsand in the hospitals, which conductedwere trained by interviewers Cases: serial 210; patients with stomach cancer from four major teaching hospitals in Taipei City Controls: hospital 810; controls, group-matched to cases by hospital, age, and sex, recruitedwere from among ophthalmic patients in study hospitals Exposure assessment method: questionnaire

(1991b)

(1990) et al.

et al. Table 2.3.4 Case–control the of cancer Table stomach and processed of meat studies consumption on (hospital-based) Reference, location, enrolment/follow-up period Lee Taiwan, City, Taipei China NA Boeing Germany 1985–1988

261 IARC MONOGRAPHS – 114 Covariates controlled Adjusted for age, sex, hospital Age, sex, hospital, vitamin C, carotene, calcium Risk estimate CI) (95% 1.00 0.88 (0.59–1.34) 3.19 (1.50–6.75) 1.00 0.93 (0.53–1.64) 0.61 (0.32–1.19) (0.30–1.27) 0.61 1.26 (0.59–2.70) Exposed cases/ deaths 68 57 18 NR NR NR NR NR

Smoking meat of home, at yes (specifying spruce) Nitrate (quintiles) Q1 Exposure category level or Smoking meat of home, at no Smoking meat of home, at wood)yes (other Q2 Q3 Q4 Q5 Organ site Population size, description, exposure assessment method Controls: group one 579; of patients of consisted controls from the hospitals, usually two controls the of same sex for each case and comparable of age; patients with a history of chronic atrophic gastritis intestinalor metaplasia were considerednot to be eligible as controls; another type of of consisted group control visitors to the hospitals, who approachedwere directly by the interviewers during their temporary stay the at hospital; the interviewers advised were to keep their selection visitor of controls within age limits similar to those the of cases Exposure assessment method: questionnaire

Table 2.3.4 Case–control the of cancer Table stomach and processed of meat studies consumption on (hospital-based) Reference, location, enrolment/follow-up period Boeing et al. (1991b) Germany 1985–1988 (cont.)

262 Red meat and processed meat Covariates controlled Age, sex, occupation, education, residency, fruit and vegetable score, non-white bread, cheese score Risk estimate CI) (95% 1.00 1.20 (0.95–1.51) 1.55 (1.07–2.26) 1.00 1.09 (0.79–1.52) 1.74 (1.00–3.01) 1.00 1.19 (0.79–1.79) 1.63 (0.85–3.15) 1.00 0.89 0.87 Exposed cases/ deaths 388 266 87 NR NR NR NR NR NR 313 268 160 value: 0.01 value: 0.09 value: 0.13 value: 0.29 P P P P

Exposure category level or Tertile 3 (high) Trend-test Sausages Tertile 1 (low) Tertile 2 Tertile 3 (high) Trend-test Sausages Tertile 1 (low) Tertile 3 (high) Trend-test Ham Tertile 1 (low) Tertile 3 (high) Trend-test Sausages Tertile 1 (low) Tertile 2 Tertile 2 Tertile 2 Organ site Stomach/ adenocarcinoma (all) Stomach/ adenocarcinoma type) (intestinal Stomach/ adenocarcinoma (diffuse type) Stomach/ adenocarcinoma (all)

Population size, description, exposure assessment method Cases: 741 (including 374 Cases: (including 374 741 and intestinalis carcinoma carcinoma259 the of diffuse- consecutive type cases); incident cases of gastric cancer (adenocarcinoma), histologically confirmed (histological diagnosis from the surgical if excision or, the patient was operable, not endoscopy-based diagnosis using the obtained biopsy material) hospital-basedControls: 741; controls admitted to the hospital surgical wards for other reasons, matched to the cases sex by and age (≥ 5 yr) Exposure assessment method: questionnaire; dietary intake measured an by FFQ including 43 single-food items; frequency was estimated a scale on of six categories (ranging from “never” to “everyday”), “no but effortswere made to quantify consumption”; food tertiles based the on distribution of frequency categories among the controls usedwere in the analysis; “processed meat” was estimated theby items “sausages” and “ham good of quality”

(1991a)

et al. Table 2.3.4 Case–control the of cancer Table stomach and processed of meat studies consumption on (hospital-based) Reference, location, enrolment/follow-up period Boeing Poland (nine university hospitals) 1986–1990

263 IARC MONOGRAPHS – 114 Covariates controlled Age, sex, residence, status, urban/rural duration,tobacco total alcohol consumption, mate drinking; red barbecued meat, meat, salted meat, processed meat, vegetables, and fruits were also included in the model Risk estimate CI) (95% (0.42–0.67) 0.53 0.96 (0.79–1.17) Exposed cases/ deaths NR NR Exposure category level or Nitrite Processed meat Organ site Stomach

Population size, description, exposure assessment method Cases: 340; all newly diagnosed and microscopically confirmed patients with gastric cancer admitted to the four major hospitals in Montevideo Controls: 698; all controls selectedwere from the same hospitals and in the same period as the cases; controls agedwere 25–84 free yr, of conditions related to digestive tract or nutritional disorders, and free of conditions related to tobacco and alcohol consumption Exposure assessment method: questionnaire

(1998) et al. Table 2.3.4 Case–control the of cancer Table stomach and processed of meat studies consumption on (hospital-based) Reference, location, enrolment/follow-up period De Stefani Montevideo, Uruguay 1993–1996

264 Red meat and processed meat Covariates controlled sex Age, Risk estimate CI) (95% 1.03 (0.86–1.22) (0.61–1.26) 0.87 Exposed cases/ deaths NR NR Exposure category level or Risk frequency by sausage for ≥ 3 times/wk vs < 3 times/ wk, without gastric cancer history family ≥ 3 times/wk vs < 3 times/ wk, with gastric cancer history family Organ site Stomach

Cases: 1988; a total of 80 420 of first-visitoutpatients who visited the Aichi Cancer Center Hospital between January 1988 and June 1998; 8057 outpatients excludedwere to due interviewer absence, inadmissible age (younger than visit or yr), a for 18 consultation; the questionnaire was finally administered to 72 363 subjects; among them, completed the (98.5%) 71 277 questionnaire adequately; after linkage between questionnaire data and medical data, 9032 excluded, were subjects (12.7%) as the cancer history least at of their of one parents siblings or was unknown Controls: 50 706; first-visitnon- cancer subjects were regarded as the group referent Exposure assessment method: questionnaire; FFQ Population size, description, exposure assessment method

(2004) et al. Table 2.3.4 Case–control the of cancer Table stomach and processed of meat studies consumption on (hospital-based) Reference, location, enrolment/follow-up period Huang Nagoya, Japan 1988–1998

265 IARC MONOGRAPHS – 114 Covariates controlled Age, residence, BMI, smoking status, smoking cessation, number of cigarettes smoked per day among current smokers, alcohol mate drinking, consumption, total energy intake, total vegetable and fruit intake, total white meat and red meat intake. Risk estimate CI) (95% 0.64 (0.49–0.83) 1.02 (0.86–1.21) 0.99 (0.87–1.14) 0.99 (0.86–1.15) 1.22 (1.03–1.44) 1.49 (1.30–1.70) 0.96 (0.81–1.14) 1.02 (0.87–1.19) 0.72 (0.46–1.13) (0.88–1.53)1.16 1.25 (1.01–1.56) (0.58–0.99) 0.76 1.48 (1.07–2.04) 1.50 (1.23–1.83) 1.24 (1.03–1.44) (0.36–1.07) 0.62 1.00 1.60 (1.02–2.49) 1.93 (1.25–2.98) 1.00 3.07 (1.58–5.98) 4.51 (2.34–8.70) Exposed cases/ deaths NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR

value: 0.003 0.0001 value: P P Exposure category level or Sausage Mortadella Salami Saucisson Hot dog Ham Salted meat Processed meat type by Women Bacon Sausage Mortadella T2 (11.5–28.2 g/day) 28.3 g/day)T3 (≥ Trend-test Processed meat Women g/day) T2 (11.5–28.2 28.3T3 (≥ g/day) Trend-test Processed meat type by Men Bacon Salami Saucisson Hot dog Ham Salted meat Processed meat Men g/day) 11.4 (< T1 g/day) 11.4 (< T1 Organ site Stomach = 274) = 274) n

Population size, description, exposure assessment method Cases: incident 234 274; cases stomachof cancer ( diagnosed in the four major hospitals in Montevideo and microscopically confirmed (C15) Controls: 2532; hospital- based controls the (from same hospitals) with conditions unrelated to tobacco smoking and alcohol drinking Exposure assessment method: questionnaire; dietary intake measured an by FFQ including 64 food items (quantities recorded as servings/wk) and tested for reproducibility with good results; “processed meat” was sausage, bacon, mortadella, salami, saucisson, dog, hot ham, and air-dried and salted lamb; intakes energy- were adjusted the by residual method

(2012) et al.

Table 2.3.4 Case–control the of cancer Table stomach and processed of meat studies consumption on (hospital-based) Reference, location, enrolment/follow-up period De Stefani Uruguay 1996–2004 BMI, body mass index; CI, confidence intervals; FFQ,food frequency questionnaire; mo, month;NA, not available; NR, not reported

266 Red meat and processed meat Covariates controlled Total food consumption and ethnicity Matched by age, sex, area of residence, and adjusted for total consumption, food ethnicity, and consumption of grains, chocolate, eggs, foods, fibrous and public water supply Risk estimate CI) (95% 2.22 (1.19–4.15) 1.71 (1.24–2.37) 0.66 (0.54–0.81) 0.94 (0.14–6.13) 3.92 (1.76–8.75) Exposed cases/ deaths 246 246 246 246 246

Exposure category level or Smoked meats (per g/day 100 increase) Nitrite (1 mg/day) Nitrate (100 g/day) Dimethylnitrosamine μg/day) (10 Smoked meats g/day (per 100 increase) Organ site Stomach

Population size, description, exposure assessment method Cases: 246; aged yr 35–79 with newly diagnosed gastric cancer; all cases histologically were verified Controls: 246; randomly selected population controls; individually matched age, by sex, and area of residence Exposure assessment method: questionnaire

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period Risch et al. (1985) Winnipeg,Toronto, Canadaand St John’s, 1979–1982

267 IARC MONOGRAPHS – 114 Covariates controlled sex Age, Risk estimate CI) (95% 1.00 0.62 1.04 1.00 0.56 1.27 1.00 0.95 0.77 Exposed cases/ deaths 75 37 94 114 31 61 187 15 4 Exposure category level or Raw ham intake (frequency) Low Intermediate High Salami and other sausages intake (frequency) Low Intermediate High Canned meat intake (frequency) Low Intermediate High Organ site Stomach

Population size, description, exposure assessment method Cases: 206; incident cases of histologically confirmed gastric cancer diagnosed within the year preceding the interview and admitted to the National Cancer Institute, to several university clinics (chiefly surgery), to and the Ospedale Maggiore in Milan Controls: hospital-based 474; controls who admitted were to the Ospedale Maggiore in Milan and to several university clinics; patients admitted for malignant disorders, any disease the of digestive tract, or any condition related to consumption of alcohol tobaccoor that might resulted have in modificationof the diet were excluded Exposure assessment method: questionnaire; dietary intake was based an on FFQ including 29 food items; individuals were asked to indicate the frequency of consumption these of items per week before the onset the of disease that led to hospital admission and to recall any major change in frequency intake of the of same foods during the 10-yr period preceding the diagnosis; items related to processed meat “ham”, ham”, “salami “raw were and other sausages”, and “canned meat”

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period La et Vecchia al. (1987) Greater Milan area, Italy 1985–June January 1986

268 Red meat and processed meat Covariates controlled Matched year by of birth, sex, municipality of residence Age, sex, total calories, chilli pepper consumption, added salt, history of peptic ulcer, cigarette smoking, socioeconomic status Risk estimate CI) (95% 1.00 3.34 (1.51–7.37) 1.00 3.55 (1.59–7.94) 1.0 2.0 (1.0–3.8) 2.8 (1.4–5.7) 3.2 (1.5–6.6) 1.0 2.2 (0.9–5.2) 2.6 (1.0–6.4) 2.6 (1.0–7.0) 1.0 1.1 (0.5–2.8) 1.8 (0.7–4.6) 2.2 (0.8–6.0) Exposed cases/ deaths 13 42 9 40 25 67 68 60 NR NR NR NR NR NR NR NR value: 0.002 P Exposure category level or Homemade sausages, not consumed Homemade sausages, daily consumption Smoked sausages, not consumed Smoked sausages, daily consumption Processed meat intake (times/wk) < 1 1–2 3–5 ≥ 6 Trend-test Processed meat intake (times/wk) < 1 1–2 3–5 ≥ 6 Processed meat intake (times/wk) < 1 1–2 3–5 ≥ 6 Organ site Stomach Stomach/ adenocarcinoma Stomach/ adenocarcinoma (intestinal) Stomach/ adenocarcinoma (diffuse)

Population size, description, exposure assessment method Cases: total 109; cases diagnosed between and 1975 a specific 1986 at study site Controls: 123; all people born locally who or had been living in the area the for past yr; 10 one control was randomly selected and matched year by birth, of sex, and municipality of residence Exposure assessment method: questionnaire Cases: 220; 267 newly diagnosed cases gastric of cancer in patients aged 20 yr and older were identified between1989 and 1990 metropolitan 15 at area hospitals in Mexico City; these cases represented approximately 80% those of reported to the Mexican Cancer Registry in the same period; the of 22 (8.2%) identified caseswere unavailable interview;for a further 20 cases excluded were because the (7.5%) pathology material could not be obtained, were and five (1.9%) cases excluded because their tumours adenocarcinomas not were the of stomach Controls: controls 752; an were age- stratified random sampleMexicoof City metropolitan area residents selected from the 1986–1987 household sampling frame of the Mexican National Survey for Health and Nutrition Exposure assessment method: questionnaire

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period Sanchez-Diez et al. (1992) Province of León, Spain 1975–1986 & López-Ward Carrillo (1999) Mexico City, Mexico 1989–1990

269 IARC MONOGRAPHS – 114 Covariates controlled Adjusted for non- dietary variables sex,(age, social class, family history of gastric cancer, area of residence, BMI total), energy, consumption tertiles of each food of interest (reference, lowest tertile) Age, sex, smoking, drinking Risk estimate CI) (95% 1.0 1.0 (0.5–2.4) 1.0 (0.4–2.6) 1.0 1.2 (0.6–2.3) 1.9 (1.0–3.7) 1.00 3.82(2.24–6.50) 2.36 (1.08–5.15) Exposed cases/ deaths NR NR NR NR NR NR NR NR NR

value: 0.1 value: 0.05 value: 0.001

P P P Exposure category level or Cured and canned meat intake, MSI+ Tertile 1 Tertile 2 Tertile 3 Trend-test Cured and canned meat intake, MSI– Tertile 1 Tertile 2 Tertile 3 Trend-test Salted meat, < 1 time/mo Salted meat, times/mo 1–3 Salted meat, ≥ 1 time/wk Trend-test Organ site Stomach Stomach

Population size, description, exposure assessment method Cases: 382; all gastric cancer cases histologicallywere confirmed and originally classified according to the Lauren classificationreviewby allof available surgical pathology specimens Controls: computerized 561; lists residentsof used were to identify a random sample eligible of population controls Exposure assessment method: questionnaire Cases: stomach 187 cancer; incident cases of histopathologically confirmed casesof stomach cancer who visited the Pizhou City Municipal Hospital Controls: healthy 333; residents of Pizhou, matched to cases sex, by ethnicity, controls 2 yr); and age (≤ came from three different sources: individuals from a population- based ecological study conducted selected individuals 1995–1996; in between and 1995 1998 in the general population; individuals selected between 1998 and 2000 Exposure assessment method: consumption food questionnaire; frequency was measured the at time the of interview yr and 10 previously; among the available items, only “salted meat” could be used to estimate “processed meat” consumption; previously used in a case–control and ecological study

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period Palli et al. (2001) Florence, Italy 1985–1987 Takezaki et al. (2001) Pizhou, Jiangsu China Province, 1996 (1995 for controls)–2000

270 Red meat and processed meat Covariates controlled Age, sex, energy intake, respondent type, BMI, alcohol use, tobacco use, education, family history, vitamin usesupplement Risk estimate CI) (95% 1.00 (0.77–3.70) 1.70 1.20 (0.55–2.70) 1.70 (0.72–3.90) Exposed cases/ deaths NR NR NR NR Exposure category level or Processed quartiles meat (times/day), Q1 Q2 Q3 Q4 Organ site Stomach/distal adenocarcinoma

Population size, description, exposure assessment method Cases: 124 (distal stomach); incident, histologically confirmed cases of stomach adenocarcinoma, identified from Nebraska the Cancer Registry participating 14 or hospitals covering > 90% the of study population Controls: 449; population-based controls selected from the control group a previous of case–control study conducted in 1986–1987 in the same base population; frequency-matched to the whole distribution cases of age, by sex, and vital status Exposure assessment method: questionnaire; dietary assessment was based a modified on version theof short HHHQ, with the addition of several food items processed for (e.g. subjects meat); askedwere to recall frequency of consumption 54 of dietary items before “processed 1985; meat” was bacon; sausage, including breakfast sausage; processed smoked or ham bought from the store; meat that was cured smoked or home; at sandwich meats, such as bologna or salami; and dogs hot

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period Chen et al. (2002) Nebraska, Eastern USA June 1 July 1988–31 1993

271 IARC MONOGRAPHS – 114 Covariates controlled Age, ethnicity, smoking, education, history of gastric ulcer, NSAID use, family history of gastric cancer, total calories, intake of other foods and food groups Age, sex, education, smoking, calories from food Risk estimate CI) (95% 1.0 1.8 (1.0–3.3) 1.7 (0.9–3.3) 1.0 0.6 (0.3–1.3) (0.3–1.5) 0.7 1.0 1.3 (0.7–2.2) 1.3 (0.7–2.4) 1.0 0.6 (0.3–1.3) 1.1 (0.5–2.3) 1.00 1.13 (0.74–1.71) 0.75 (0.48–1.17) 1.23 (0.79–1.93) Exposed cases/ deaths NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR

value: 0.19 value: 0.43 value: 0.36 value: 0.4 value: 0.81 P P P P P

Exposure category level or Processed meat Men T1 T2 T3 Trend-test Processed meat, Tertiles Women T1 T2 T3 Trend-test Tertiles Bacon, Men T1 T2 T3 Trend-test Bacon Women T1 T2 T3 Trend-test Sausages ,Quartiles (frequency/wk) Q1 Q2 Q3 Q4 Trend-test Organ site Stomach Stomach

Population size, description, exposure assessment method Cases: 658; from eight major hospitals the on Hawaiian Islands and identifiedby the rapid reporting system the of Hawaii RegistryTumor Controls: 446; controls identified from lists Oahu of residents interviewed the by Health Surveillance Program, which identifies1% representative a random sample of all households in the state Exposure assessment method: questionnaire Cases: cases 274; consisted of Warsaw residents newly diagnosed with stomach cancer; identified by collaborating physicians in each of the 22 hospitals Controls: 463; controls randomly selected from the general population in Warsaw Exposure assessment method: questionnaire

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period Nomura et al. (2003) Hawaii, USA 1993–1999 Lissowska et al. (2004) Poland Warsaw, 1994–1996

272 Red meat and processed meat ), reflux,), use 2 Covariates controlled Age, sex, race, birthplace, education, smoking, BMI (kg/ m of vitamins, total calories

, , H. pylori H. pylori Risk estimate CI) (95% 1.00 0.84 (0.60–1.30) 0.76 (0.50–1.20) 0.89 (0.60–1.40) 1.00 1.54 (1.10–2.20) 1.22 (0.80–1.80) 1.65 (1.10–2.50) 1.00 1.16 (0.60–2.40) 0.40 (0.20–0.96) 0.57 (0.20–1.30) 1.00 2.46 (1.10–5.20) 1.40 (0.60–3.10) 1.97 (0.90–4.50) Exposed cases/ deaths NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR value: 0.57 0.049 value: value: 0.08 value: 0.3 P P P P Exposure category level or Processed meat, quartiles (g/day) Q1 Q2 Q3 Q4 Trend-test Processed meat, quartiles (g/day) Q1 Q2 Q3 Q4 Trend-test Processed meat among subjects infected with quartiles intake of (g/day) Q1 Q2 Q3 Q4 Trend-test Processed meat among subjects infected with quartiles intake of (g/day) Q1 Q2 Q3 Q4 Trend-test Organ site Stomach/cardia adenocarcinoma Stomach/distal adenocarcinoma Stomach/cardia adenocarcinoma Stomach/distal adenocarcinoma

Population size, description, exposure assessment method Cases: 829; all incident cancers identifiedwere by the Los Angeles Cancer Surveillance Program, a population-based tumour registry Controls: 1308; control subjects were individually matched to interviewed case patients sex, by race, and date birth of in (± 5 yr) the neighbourhoods Exposure assessment method: questionnaire

273 IARC MONOGRAPHS – 114 Covariates controlled Sex; site; age, “race”; proxy status; income; education; usual BMI; cigarettes per day; consumption wine, beer, of and liquor each; energy intake Risk estimate CI) (95% 1.19 (0.74–1.91) 1.88 (1.24–2.84) Exposed cases/ deaths NR NR NR NR Exposure category level or High-nitrite meats, for an increase in intake of 1 serving/day High-nitrite meats, for an increase in intake of 1 serving/day Organ site Stomach/cardia adenocarcinoma Stomach/ non-cardia adenocarcinoma Population size, description, exposure assessment method Cases: incident 607; cases of stomach adenocarcinoma (255 non-cardia 352 cases, cardia cases); this population was part of a larger population cases of also containing cases cardia of and non- adenocarcinoma; gastric cardia gastric cardia adenocarcinoma consideredwere as the “target gastric non-cardia whereas cases”, adenocarcinoma cases were considered as the “comparison case which group”, was frequency- matched to the “target group”

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period Navarro Silvera et al. (2008) Connecticut, New Jersey and western Washington, USA 1993–early 1995

274 Red meat and processed meat Covariates controlled Risk estimate CI) (95% Exposed cases/ deaths Exposure category level or Organ site Population size, description, exposure assessment method Controls: population-based 687; controls frequency-matched to the expected distribution the of “target cases” 5-yr by age group, sex New Jersey (in and Washington “race” New and Jersey), (in state), study site; controls aged 30–64 yr identifiedwere by the random digit dialling method, and controls aged yr65–79 identified were Healthby Care Financing Administration rosters Exposure assessment method: questionnaire; an expanded version an of FFQ developed and validated investigators by the at Fred Hutchinson Cancer Research Center was used to assess usual food consumption in the period 3–5 yr before diagnosis or (cases) interview processed (controls); meat was defined as “ high-nitrite includingmeats”, smoked turkey lunchmeat; cured, smoked ham lunchmeat; bologna; salami; dogs;hot sausage, including not breakfast sausage; bacon; and sausage breakfast

275 IARC MONOGRAPHS – 114 H. pylori Covariates controlled Sex, age group, education, family history of gastric cancer, citrus fruits, garlic, onion, red meat, fish, dairy products, strength and warmth tea, of preference for salt intake, Risk estimate CI) (95% (0.40–2.09) 0.91 1.00 1.14 (0.55–2.37) 1.00 Exposed cases/ deaths 20 189 23 188 Exposure category level or Smoked meats, ≥ 1 time/mo Smoked meats, never Processed meats, ≥ 1 time/mo Processed meats, never Organ site Stomach

Population size, description, exposure assessment method identifiedCases: from 217; the Ardabil Cancer Registry; cases eligiblewere if they in were people who had been Ardabil residents for leastat 5 yr before diagnosis, were aged older than had yr, had not 18 previous gastric surgery, and had a positive histopathological report gastricof carcinoma; in addition to the cases routinely reported to the cancer registry, active surveillance gastricfor cancer was conducted theby cancer registry through all particularly clinics, and hospitals those of three gastroenterologists, to maximize the completeness of ascertainment case Controls: 394; two controls were sought each for case and frequency- matched to the case group age by (5 andyr) sex; controls had to satisfy the same residency and age criteria as cases, and randomly were selected from the community using a computer-based sampling frame that had been created for the annual household survey theby health department; this database was used to select random households, which then were visited by health professionals seeking eligible individuals; if such a person was available not did or satisfynot the inclusion criteria, the immediate neighbour to the right-hand side was visited Exposure assessment method: questionnaire

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period Pourfarzi et al. (2009) Ardabil Province, Iran 2004–2005

276 Red meat and processed meat

Covariates controlled Age, province, education, BMI, alcohol drinking, smoking, vegetable and fruit intake, total energy Age, sex, smoking status,, education, vitamin C, fibre, carbohydrates, total calories Risk estimate CI) (95% 1.0 1.2 (1.0–1.6) 1.3 (1.0–1.7) 1.7 (1.3–2.2) 1.00 (0.45–1.46) 0.81 1.17 (0.66–2.10) (0.51–1.85) 0.97 1.03 (0.97–1.10) Exposed cases/ deaths NR NR NR NR 30 38 40 46 NR ; HHHQ, Health Habits and History Questionnaire; mo, month; value: 0.0001 value: value: 0.87 P P Helicobacter pylori , Exposure category level or Processed meat (servings/wk) ≤ 0.94 0.95–2.41 2.42–5.41 ≥ 5.42 Trend-test Processed meat g/day) 16.1 (≤ Q1 Q2 (16.2–29.6 g/day) (29.7–52.3 g/day) Q3 52.3Q4 g/day) (> (per 10 g/day) OR Trend-test H. pylori Organ site Stomach Stomach

Population size, description, exposure assessment method Cases: this study 1182; involved histologically confirmed cancer cases Controls: 5039; individuals without cancer selected were from a random sample the of population within each province, with an age and sex distribution similar to that allof cancer cases Exposure assessment method: questionnaire Cases: stomach; 154 for incident cases adenocarcinoma of the of stomach, identified from the Nebraska Cancer Registry and confirmedby histologicalreview Controls: 449; controls randomly selected from a previous population-based case–control study in the same geographical region; matched race, by age, sex, and vital status Exposure assessment method: questionnaire; dietary information was obtained using a short version theof HHHQ; “processed meat” was bacon, sausage, luncheon meats, dogs, hot ham, and home- cured meat

Table 2.3.5 Case–controlTable the of cancer studies stomach and processed of meat (population-based) consumption on Reference, location, enrolment/follow-up period et al.Hu (2011) Canada 1994–1997 et al.Ward (2012) counties (66 USA in Nebraska) eastern 1 July 1988–30 June 1993 BMI, body mass index; CI, confidence intervals; FFQ,food frequency questionnaire; MSI, microsatellite instability; NR, not reported; OR, odds ratio

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