We analyzed the potential role of pizza on cancer risk, using data from an integrated network of case‐control studies conducted in Italy between 1991 and 2000. Cancer sites were: oral cavity and pharynx (598 cases), esophagus (304 cases), larynx (460 cases), colon (1,225 cases) and rectum (728 cases). Controls were 4,999 patients admitted for acute, non‐neoplastic conditions to the same hospital network as cases. Odds ratios for regular pizza consumers were 0.66 (95% confidence interval, CI = 0.47–0.93) for oral and pharyngeal cancer, 0.41 (95% CI = 0.25–0.69) for oesophageal, 0.82 (95% CI = 0.56–1.19) for laryngeal, 0.74 (95% CI = 0.61–0.89) for colon and 0.93 (95% CI = 0.75–1.17) for rectal cancer. Pizza appears therefore to be a favorable indicator of risk for digestive tract neoplasms in this population. © 2003 Wiley‐Liss, Inc.

Pizza is one of the best known and most widespread Italian foods, and it is said to be the most common generic commercial sign of Italy worldwide. Investigating and quantifying any potential role of pizza on cancer risk seems to be a curious issue, but may well have interesting implications in respect to dietary advice in Italy as well as elsewhere. Limited and inconclusive information is available on the potential influence of pizza, however, as a food item or as an indicator of any specific dietary pattern, on cancer risk. An inverse trend in risk with increasing number of portions of pizza was observed for prostate cancer in the U.S. Health Professionals Follow‐Up Study.1, 2 In a case‐control study from southern Italy on 132 cases of colorectal cancer, the odds ratio (OR) for frequent consumption of pizza was 0.89 (95% confidence interval, CI = 0.51–1.53).3 We analyzed data from a large and integrated network of case‐control studies conducted in Italy, including detailed information on pizza eating as well as on a large number of potential confounding factors.

MATERIAL AND METHODS Case‐control studies on digestive tract and laryngeal neoplasms have been conducted between 1991 and 2000 in various regions of northern, central and southern Italy.4, 5, 6, 7 Our analysis included 598 patients (512 men, 86 women) with incident, histologically confirmed cancer of the oral cavity and pharynx, 304 (275 men, 29 women) with squamous‐cell oesophageal cancer, 460 (415 men, 45 women) with cancer of the larynx, 1,225 (688 men, 537 women) of the colon and 728 (437 men, 291 women) of the rectum. The comparison group included 4,999 patients (2,724 men, 2,275 women) admitted to the same hospital network as cases for acute, non‐neoplastic diseases. Twenty‐five percent of controls were admitted for traumas, 30% for other non‐traumatic orthopaedic conditions, 18% for acute surgical disorders and 27% for miscellaneous other illnesses. Response rate was more than 95% for both cases and controls. All subjects were interviewed using a standard questionnaire, including information on socio‐demographic factors and lifestyle habits, such as tobacco smoking and alcohol consumption. Subjects' usual diet before diagnosis (or hospital admission) was investigated using a validated 78‐item food frequency questionnaire8, 9 that included a specific question on pizza. For the present analyses, pizza eating was classified in 3 categories: non eaters (<1 portion of pizza/month), occasional eaters (1–3 portions/month) and regular eaters (1 portion of pizza or more/week). OR and the corresponding 95% CI, for subsequent levels of pizza eating were derived by unconditional multiple logistic regression models, including terms for age, gender, study center, education, alcohol and tobacco consumption, energy intake, body mass index and for colon and rectum, a measure of physical activity.

RESULTS Table I shows the distribution of cases and controls according to pizza consumption and the corresponding multivariate ORs. Compared to non‐pizza‐consumers, the multivariate ORs for pizza eaters (≥1 portion/month) were 0.73 for oral cavity and pharynx, 0.53 for esophagus, 0.85 for larynx, 0.81 for colon and 0.88 for rectum. Corresponding ORs for regular pizza eaters (≥1 portion/week) were 0.66 for oral and pharyngeal, 0.41 for oesophageal, 0.82 for laryngeal, 0.74 for colon and 0.93 for rectal cancer. The trends in risk were significant for oral and pharyngeal, esophageal and colon cancers. Table I. Odds ratios (OR) and 95% confidence intervals (CI) for various Neoplasms According to Pizza Consumption in Italy 1991–2000 Cancer Pizza eaters OR (95% CI)2 χ2 trend (p)4 Non Occasional3 Regular3 Occasional3 Regular3 All eaters Oral cavity and pharynx 310 213 75 0.76 (0.60–0.95) 0.66 (0.47–0.93) 0.73 (0.59–0.91) 7.92 (0.005) Oesophagus 175 105 24 0.57 (0.42–0.78) 0.41 (0.25–0.69) 0.53 (0.39–0.72) 17.46 (<0.001) Larynx 236 167 57 0.86 (0.66–1.11) 0.82 (0.56–1.19) 0.85 (0.66–1.08) 1.71 (0.191) Colon 503 473 249 0.84 (0.72–0.97) 0.74 (0.61–0.89) 0.81 (0.70–0.93) 10.97 (0.001) Rectum 301 260 167 0.85 (0.71–1.02) 0.93 (0.75–1.17) 0.88 (0.74–1.04) 0.74 (0.390) Controls 1,836 2,016 1,147 — — — — No appreciable difference was found according to gender for colorectal cancer, the ORs of pizza consumers being 0.78 (95% CI: 0.65–0.94) in men and 0.82 (95% CI: 0.66–1.02) in women for colon cancer, and 0.91 (95% CI: 0.73–1.14) and 0.82 (95% CI: 0.63–1.08) respectively for rectal cancer (not shown in Table I). The data were inadequate to analyze women only for upper digestive and respiratory tract neoplasms.

DISCUSSION The findings of this uniquely large and integrated series of case‐control studies from Italy suggest that pizza eating is a favorable indicator of risk for digestive tract neoplasms. In contrast, major sources of refined carbohydrates in Italy, mainly bread and pasta, were directly associated with the risk of colorectal cancer4 but inconsistently related to the risk of cancer of the upper aero‐digestive tract.5, 6, 7 Pizza, however, does not include only variable amounts of carbohydrates (∼50%), but also tomato sauce (20%), mozzarella cheese (20%) and olive oil (4%), plus additional toppings in a proportion of cases. The favorable influence on the risk of the neoplasms investigated may therefore be related to tomatoes or olive oil, which have been shown to be inversely associated to the risk of various cancers, including those of the digestive tract and larynx.4, 5, 6, 7, 10, 11 Cooked tomatoes (and especially tomato sauce) are rich in lycopene, a carotenoid that has been shown inversely related to cancers of the prostate in the US,2 of the digestive tract in Italy,12 and of several other sites.2 Our study has some of the limitations and several strengths of hospital‐based case‐control studies. In particular, controls included a wide range of acute non‐neoplastic conditions unrelated to long term modification of diet, participation was almost complete, and allowance was made for tobacco, alcohol, education and other major potential confounding factors. Reproducibility of information on pizza consumption was 0.66.8 Even if the association is real, drawing inferences about specific components of pizza, nutrients or micronutrients remains difficult, because pizza may simply represent an aspecific indicator of Italian diet. Some (olive oil, fish, vegetables and fruit), though not all, aspects of Mediterranean diet have shown a favorable effect on the risk of several chronic diseases, including cancer.11, 13, 14, 15, 16 In fact, it has been estimated that a traditional healthy Mediterranean diet could prevent 10–25% of several common neoplasms in developed Western countries.10 Extension of the apparently favorable effect of pizza on cancer risk in Italy to other types of diets and populations is therefore not warranted.

Acknowledgements The authors thank Mrs. J. Baggott and M.P. Bonifacino for editorial assistance.