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.