Olio di oliva nella prevenzione. Carlo La Vecchia Università degli Studi di Milano Enrico Pira Università degli Studi di Torino

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1 Olio di oliva nella prevenzione della patologia cronicodegenerativa, con focus sul cancro Carlo La Vecchia Università degli Studi di Milano Enrico Pira Università degli Studi di Torino

2 Olive oil and cancer: a review and meta-analysis

3 Olive oil and cancer risk Olive oil is a major source of monounsaturated fats in Mediterranean countries, but also an important source of several micronutrients and food components. It appears to be a favourable indicator of the risk of various common cancers.

4 Olive oil and cancer risk We considered data from a network of large multricentric studies conducted in Italy on breast, ovarian, colorectal and upper digestive and respiratory tract cancers. We also derived meta-analytic estimates from all published studies to December 21.

5 Olive oil and cancer risk Data on breast cancer included 2,564 women hospitalized with histologically confirmed, incident breast cancer. Controls were 2,588 women admitted to the same network of hospitals for acute, nonneoplastic, non-hormone related, nondigestive tract disorders. Cases and controls were interviewed using a validated food-frequency questionnaire.

Olive oil, other seasoning fats and breast cancer Oil or fat Continuing OR (95% CI) per unit difference between 1 and 4 quintile Olive oil.89 (unit= 3 g) (.81-.

6 Olive oil, other seasoning fats and breast cancer Oil or fat Continuing OR (95% CI) per unit difference between 1 and 4 quintile Olive oil.89 (unit= 3 g) ( ) Specific seed oils.88 (unit= 9.5 g) ( ) Mixed seed oils.96 (unit= 2.8 g) (.96-1.) Butter 1. (unit= 4.5 g) ( ) Margarine.96 (unit= 4.2 g) ( ) (La Vecchia et al., 1995)

7 Olive oil and breast cancer The RR for the highest quintile was.87, and the continuous RR for a 3g/day increase was.89 (95% CI , La Vecchia et al., 1995).

8 Olive oil and breast cancer. Pooled estimates (Pelucchi et al., 211)

9 Olive oil and breast cancer All six studies of breast cancer that provided ORs according to level of olive oil consumption reported risk estimates below unity for the highest level of intake. We pooled these estimates and calculated a summary RR of.62 (95% CI, ) for the highest level of olive oil consumption. Thus, epidemiological studies collectively support an inverse association between olive oil consumption and breast cancer.

10 Breast cancer. Overall evidence Animal data, ecologic evidence, and results of analytic epidemiologic studies converge in indicating a beneficial effect of olive oil.

11 Olive oil and other cancers (Lipworth et al., 1997)

12 Ovarian cancer We analyzed data from a multicentre case control study conducted between 1992 and 1999 in Italy, including a total of 131 incident epithelial ovarian cancers and 2411 hospital controls. The subjects usual diet was investigated through a validated food-frequency questionnaire, including specific questions aimed at assessing added fat intake patterns. (Bosetti et al., 22)

13 Ovarian cancer After allowance for study centre, year at interview, age, education, parity, oral contraceptive use, and total energy intake, a reduced risk of ovarian cancer was observed for high intake of olive oil (OR =.68, 95% CI.5.93 for the highest quintile of intake, compared to the lowest one). No significant associations were observed for mixed seed oils, butter, and margarine.

Ovarian cancer RR for subsequent quintile of olive oil intake Added fat Quintile of intake 2 3 4 5 Olive oil OR 1.3.78.84.68 95% CI.77-1.38.57-1.7.62-1.14.5-.93 Specific seed oils OR.78.59 95% CI.

14 Ovarian cancer RR for subsequent quintile of olive oil intake Added fat Quintile of intake Olive oil OR % CI Specific seed oils OR % CI Mixed seed oils OR % CI Butter OR % CI Margarine OR.85 95% CI (Bosetti et al., 22)

15 Ovarian cancer The present study the largest case control investigation on diet and ovarian cancer, conducted on a population with appreciable heterogeneity of fat intake provides a suggestion for a favorable effect of olive oil, the major source of mono- and polyunsaturated fatty acids in the Italian diet. This was only partly accounted for by vegetable intake.

16 Endometrial cancer A study of 274 cases of endometrial neoplasms and 572 controls from the Swiss Canton of Vaud and two areas of northern Italy found limited evidence for a beneficial role of olive oil consumption, with ORs of.56 for intermediate and.82 for high use, compared with low use (p for trend=.54, Levi et al., 1993).

17 Colorectal cancer The relationship between various seasoning fats and colorectal carcinoma risk was investigated using data from a case-control study conducted in six Italian areas. Cases were 1953 patients with incident, colorectal carcinoma (1225 of the colon and 728 of the rectum). Controls were 4154 subjects with no history of cancer. (Braga et al., 1998)

18 Colorectal cancer The ORs for successive tertiles of olive oil intake, compared with the lowest one, were.87 and.83 when colorectal carcinoma was analyzed as a whole,.82 and.81 for colon carcinoma, and.96 and.88 for rectal carcinoma.

Olive oil and colorectal cancer Tertile of intake Allowance for vegetable intake 2 3 (high) Olive oil Colorectal No.87 (.75-1.1).83 (.7-.99) Yes.92 (.79-1.7).94 (.

19 Olive oil and colorectal cancer Tertile of intake Allowance for vegetable intake 2 3 (high) Olive oil Colorectal No.87 ( ).83 (.7-.99) Yes.92 ( ).94 ( ) Colon No.82 ( ).81 ( ) Yes.87 ( ).94 ( ) Rectum No.96 ( ).88 ( ) Yes 1. ( ).97 ( ) (Braga et al., 1998)

20 Colorectal cancer. Italian studies Seasoning fats did not appear to increase the risk of colorectal carcinoma, and there was little evidence for a differential effect by fat type. If such a differential effect exists, it could favor olive oil. (Braga et al., 1998)

21 Fried foods, fats added to cooking and colorectal cancer Total fried food Type of oil Olive oil Specific-seed oils Mixed-seed oils Colon OR (95% CI) ( ) ( ) (.9-1.6) Rectum OR (95% CI) ( ) ( ) ( ) Colorectum OR (95% CI) (.86-1.) ( ) ( ) (Galeone et al., 27)

22 Fried foods, fats added to cooking and colorectal cancer Our results do not indicate a relevant role of fried foods on colorectal cancer risk in Italy. We found a possible favorable effect of (fried) olive oil on colon cancer risk. (Galeone et al., 27)

23 Colorectal cancer-summary results (Pelucchi et al., 211)

24 Stomach cancer- summary results (Pelucchi et al., 211)

25 Stomach cancer The earliest study of gastric cancer, conducted in four areas of Italy between 1985 and 1987, was based on 116 cases and 1159 controls and focused on various dietary items and food groups. Subjects reporting daily consumption of olive oil, compared with those with less frequent use, had a significantly decreased OR of gastric cancer (OR=.8, 95% CI,.6-.9), adjusted for several covariates, but not energy intake (Buiatti et al., 1989).

26 Stomach cancer A second analysis was based on a subset of participants from the same study, including 126 cases tested for microsatellite instability (MSI) status and 561 controls. After adjustment for selected non-dietay covariates and total energy intake, the ORs for increasing tertiles of olive oil consumption, compared with the lowest one, were.4 (95% CI,.2-1.O) and.5 (95% CI,.2-1.1), respectively, for MSI+ cancers and.7 (95% CI,.4-1.2) and.6 (95% CI,.3-1.), for MSI- cancers (Pardi et al., 21).

27 Pancreatic cancer An inverse relation between olive oil use and pancreatic cancer risk was reported in a study conducted in Milan, Italy, between 1983 and Information on use of seasoning fats was collected using a selfreported score. As compared to low use of olive oil, the ORs were.76 (95% CI, ) for intermediate use and.6 (95% CI, ) for high use (p for trend<.5, La Vecchia and Negri, 1997).

28 Oral and pharyngeal cancers Cases were 512 men and 86 women with cancers of the oral cavity and pharynx, and controls were 18 men and 483 women who had been admitted to hospital for a broad range of acute non-neoplastic conditions (Franceschi et al., 1999).

29 Olive oil, other seasoning fats and oral and pharyngeal cancers (Franceschi et al., 1999)

30 Oral and pharyngeal cancers High intake of olive oil (OR in highest vs lowest quintile =.4, 95% CI:.3.7) was associated with significantly lowered risk. The beneficial effect of olive oil was attenuated by the introduction of vegetable intake in the model. Mixed seed oils and margarine were not related to cancer risk, whereas a strong positive association emerged for butter (OR = 2.3, 95% CI: , Franceschi et al., 1999).

31 Olive oil and oral and pharyngeal cancers In terms of potential biologic mechanisms, olive oil may have antioxidant properties. It is not clear whether such activity is due to oleic acid itself or to the presence of other antioxidants, such as vitamin E and polyphenols, in olive oil. Fat intake patterns exerted a stronger influence on the risk of cancer of the oral cavity and pharynx than on colorectal cancer or breast cancer in companion Italian studies.

32 Olive oil and esophageal cancer We conducted a case-control study in 3 areas of northern Italy, including a total of 34 incident, histologically confirmed cases of squamous cell carcinoma of the esophagus (275 men, 29 women) and 743 hospital controls (593 men, 15 women) with acute, non-neoplastic conditions, not related to smoking, alcohol consumption or long-term diet modification. (Bosetti et al., 2)

33 Olive oil and esophageal cancer Olive oil intake showed a significant reduction of cancer risk (OR=.3, 95% CI.1.5 for the highest vs. the lowest quintile), while butter consumption was directly associated with cancer risk (OR 2.2, 95% CI ). No significant associations emerged with consumption of specific seed oils, mixed seed oils or margarine. The introduction into the model of total vegetables slightly reduced the association between olive oil and cancer risk, which however remained significant.

34 Olive oil, other seasoning fats and esophageal cancer (Bosetti et al., 2)

35 Olive oil and laryngeal cancer Besides tobacco and alcohol, diet has been associated with laryngeal cancer risk. We analyzed the role of various food groups, as well as specific seasoning fats, in a case-control study conducted in Northern Italy and the Swiss Canton of Vaud. This study included 527 incident, histologically confirmed cases and 1,297 frequency-matched controls, selected among patients admitted to the same hospitals as cases for acute, nonneoplastic conditions, unrelated to smoking, alcohol consumption and long term modifications of diet. (Bosetti et al., 22)

36 Olive oil, other seasoning fats and laryngeal cancer A significant reduction of cancer risk was observed for olive oil (OR.4, 95% CI:.3.7, for the highest compared to the lowest quintile) and specific seed oils (OR.6, 95% CI:.4.9), while mixed seed oils were directly associated with laryngeal cancer risk (OR 2.2, 95% CI: ). No significant associations emerged for consumption of butter and margarine.

37 Olive oil, other seasoning fats, and laryngeal cancer (Bosetti et al., 22)

38 Olive oil and laryngeal cancer As for other neoplasms, this could be explained by antioxidant properties, due both to oleic acid itself and to the presence of other antioxidants, such as vitamin E and polyphenols. The observed associations may not be due to specific components of olive oil, but to the fact that these are indicators of healthier dietary habits, and possibly other beneficial lifestyle factors.

39 Olive oil and UADT cancer The largest study providing information on olive oil consumption and risk of UADT cancers overall was a multicentre European investigation (the ARCAGE study) that provided data on olive oil intake from 1981 cases and 1993 controls enrolled in 9 countries. Compared with subjects with consumption below the centrespecific median value, those with intake above the median had ORs of.78 (95% CI,.67-.9) for overall olive oil consumption,.84 (95% CI,.7-1.) for olive oil use in salads and.65 (95% CI, ) for use for cooking (Lagiou et al., 29).

40 Olive oil and UADT cancers: summary results (Pelucchi et al., 211)

41 Olive oil and UADT cancers In conclusion, the evidence, though limited, is suggestive of a protective effect of olive oil consumption on the risk of UADT cancers. Though the described studies differed in the categories of consumption considered and were conducted in different European countries, they all reported significant inverse associations between olive oil and cancer, with reductions in risk from 22% to 74% for the highest consumption.

42 Olive oil and other cancers Scattered evidence suggests a favourable effect of olive oil in lung, prostate, bladder and thyroid cancer.

43 Olive oil and other cancers

44 Mediterranean diet score and cancers of the upper digestive tract An a priori defined score (Trichopoulou et al., 1995), summarising eight of the major characteristics of the Mediterranean diet and including olive oil, was applied to data of case-control studies of oral (n=599), oesophageal (n=34) and laryngeal (n=46) cancers (Bosetti et al., 23).

45 Mediterranean diet score and cancers of the upper digestive tract (Bosetti et al., 23)

Mediterranean diet score and cancers of the upper digestive tract Cancer Mediterranean diet score (number of characteristics) <3 4 6 Oral/pharyngeal Cases/controls 214/241 12/376 41/21 OR (95% CI) 1.

46 Mediterranean diet score and cancers of the upper digestive tract Cancer Mediterranean diet score (number of characteristics) <3 4 6 Oral/pharyngeal Cases/controls 214/241 12/376 41/21 OR (95% CI) 1.41 (.3-.57).4 ( ) Oesophageal Cases/controls 12/147 66/174 14/83 OR (95% CI) 1.63 ( ).26 ( ) Laryngeal Cases/controls 183/225 98/279 19/124 OR (95% CI) 1.47 ( ).23 (.13-.4) (Bosetti et al., 23)

47 Mediterranean diet score and cancers of the upper digestive tract An a priori defined nutritional pattern, which includes olive oil and several aspects of the Mediterranean diet, favourably affects the risk of cancers of the upper aerodigestive tract.

48 Pizza and cancer risk Pizza is one of the best known and most widespread Italian foods, and it is the most common generic commercial sign worldwide. Investigating the role of pizza on cancer risk may have interesting implications in respect to dietary advice not only in Italy.

50 Pizza and cancer risk (Gallus et al., 23)

51 Pizza and cancer risk The favourable influence on the risk of the neoplasms investigated may be related to olive oil, tomatoes or other components.

52 Pizza and cancer risk Inference about specific components of pizza, nutrients or micronutrients remains difficult, because pizza may simply represent an aspecific indicator of Italian diet. Role of selected indicator questions.

53 Conclusions 1 Olive oil and cancer risk Large and multricentric Italian studies, and meta-analyses, showed that olive oil is a favourable indicator of breast, ovarian, colorectal, but mostly of upper digestive and respiratory tract cancers. For these neoplasms, the RR difference between extreme levels of olive oil versus butter consumption reached a factor 4 to 5, pointing to olive oil as a relevant factor of Mediterranean diet on cancer risk.

54 Conclusions 2 Preferring olive oil to other added lipids, particularly those rich in saturated fats, may decrease risk of UADT neoplasms, as well as breast and, possibly, colorectal and other selected cancer sites. Given the high incidence of these neoplasms, increasing olive oil consumption may represent a relevant approach towards cancer prevention.

55 Conclusions 3 Control of body weight is a priority. Still, overweight has not been increasing over the last 2 decades in Italy.

56 Overweight in Italian adults % prevalence (Gallus et al., 26)

57 Conclusions 4 A low risk diet for cancer would not only imply increasing fruit and vegetables, avoiding increasing red meat, but also refined carbohydrate consumption, and preferring olive oil and other unsaturated fats to saturated ones.

Alcol e tumori con focus sulle basse dosi

Alcol e tumori con focus sulle basse dosi Carlo La Vecchia Department of Epidemiology, Istituto Mario Negri Department of Clinical Sciences and Community Health, Università degli Studi di Milano 1 Cancers