Cancer Causes & Control

, Volume 21, Issue 2, pp 237–242 | Cite as

Citrus fruit and cancer risk in a network of case–control studies

  • Roberto Foschi
  • Claudio PelucchiEmail author
  • Luigino Dal Maso
  • Marta Rossi
  • Fabio Levi
  • Renato Talamini
  • Cristina Bosetti
  • Eva Negri
  • Diego Serraino
  • Attilio Giacosa
  • Silvia Franceschi
  • Carlo La Vecchia
Original paper



Citrus fruit has shown a favorable effect against various cancers. To better understand their role in cancer risk, we analyzed data from a series of case–control studies conducted in Italy and Switzerland.

Patients and methods

The studies included 955 patients with oral and pharyngeal cancer, 395 with esophageal, 999 with stomach, 3,634 with large bowel, 527 with laryngeal, 2,900 with breast, 454 with endometrial, 1,031 with ovarian, 1,294 with prostate, and 767 with renal cell cancer. All cancers were incident and histologically confirmed. Controls were admitted to the same network of hospitals for acute, nonneoplastic conditions. Odds ratios (OR) were estimated by multiple logistic regression models, including terms for major identified confounding factors for each cancer site, and energy intake.


The ORs for the highest versus lowest category of citrus fruit consumption were 0.47 (95% confidence interval, CI, 0.36–0.61) for oral and pharyngeal, 0.42 (95% CI, 0.25–0.70) for esophageal, 0.69 (95% CI, 0.52–0.92) for stomach, 0.82 (95% CI, 0.72–0.93) for colorectal, and 0.55 (95% CI, 0.37–0.83) for laryngeal cancer. No consistent association was found with breast, endometrial, ovarian, prostate, and renal cell cancer.


Our findings indicate that citrus fruit has a protective role against cancers of the digestive and upper respiratory tract.


Citrus Epidemiology Neoplasms Risk factors 



The authors thank Mrs. M. P. Bonifacino for editorial assistance, and Mrs. O. Volpato for study coordination (Unit of Epidemiology and Biostatistic). We are also deeply grateful to Drs. G. Chiara (I General Surgery Department), G. Tosolini (II General Surgery Department) for helping in case enrollment at the General Hospital, Pordenone, as well as to Drs. L. Forner (Eye Diseases Department), A. Mele (Hand Surgery and Microsurgery Department, and E. Trevisanutto (Dermatology Department) for providing control patients at the General Hospital, Pordenone. This study was conducted with the contribution of the Italian Association for Cancer Research and the Italian League against Cancer.


  1. 1.
    World Cancer Research Fund and American Institute for Cancer Research (1997) Food, Nutrition and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington, DCGoogle Scholar
  2. 2.
    La Vecchia C, Tavani A (1998) Fruit and vegetables, and human cancer. Eur J Cancer Prev 7:3–8CrossRefPubMedGoogle Scholar
  3. 3.
    Hung HC, Joshipura KJ, Jiang R et al (2004) Fruit and vegetable intake and risk of major chronic disease. J Natl Cancer Inst 96:1577–1584PubMedGoogle Scholar
  4. 4.
    Riboli E, Norat T (2003) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr 78:559S–569SPubMedGoogle Scholar
  5. 5.
    Vastag B (2005) Recent studies show limited association of fruit and vegetable consumption and cancer risk. J Natl Cancer Inst 97:474–476PubMedGoogle Scholar
  6. 6.
    World Cancer Research Fund and American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington, DCGoogle Scholar
  7. 7.
    Benavente-Garcia O, Castillo J, Alcaraz M, Vicente V, Del Rio JA, Ortuno A (2007) Beneficial action of citrus flavonoids on multiple cancer-related biological pathways. Curr Cancer Drug Targets 7:795–809CrossRefPubMedGoogle Scholar
  8. 8.
    Franke AA, Cooney RV, Custer LJ, Mordan LJ, Tanaka Y (1998) Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents. Adv Exp Med Biol 439:237–248PubMedGoogle Scholar
  9. 9.
    Frei B, Lawson S (2008) Vitamin C and cancer revisited. Proc Natl Acad Sci USA 105:11037–11038CrossRefPubMedGoogle Scholar
  10. 10.
    Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74:418–425PubMedGoogle Scholar
  11. 11.
    Odin AP (1997) Vitamins as antimutagens: advantages and some possible mechanisms of antimutagenic action. Mutat Res 386:39–67CrossRefPubMedGoogle Scholar
  12. 12.
    Onogi N, Okuno M, Matsushima-Nishiwaki R et al (1998) Antiproliferative effect of carotenoids on human colon cancer cells without conversion to retinoic acid. Nutr Cancer 32:20–24CrossRefPubMedGoogle Scholar
  13. 13.
    Padayatty SJ, Katz A, Wang Y et al (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22:18–35PubMedGoogle Scholar
  14. 14.
    Rauscher R, Edenharder R, Platt KL (1998) In vitro antimutagenic and in vivo anticlastogenic effects of carotenoids and solvent extracts from fruits and vegetables rich in carotenoids. Mutat Res 413:129–142PubMedGoogle Scholar
  15. 15.
    Steinmetz KA, Potter JD (1991) Vegetables, fruit, and cancer. II. Mechanisms. Cancer Causes Control 2:427–442CrossRefPubMedGoogle Scholar
  16. 16.
    Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP, Gescher AJ (2007) Dietary polyphenolic phytochemicals—promising cancer chemopreventive agents in humans? A review of their clinical properties. Int J Cancer 120:451–458CrossRefPubMedGoogle Scholar
  17. 17.
    Pavia M, Pileggi C, Nobile CG, Angelillo IF (2006) Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. Am J Clin Nutr 83:1126–1134PubMedGoogle Scholar
  18. 18.
    Bae JM, Lee EJ, Guyatt G (2008) Citrus fruit intake and stomach cancer risk: a quantitative systematic review. Gastric Cancer 11:23–32CrossRefPubMedGoogle Scholar
  19. 19.
    Bae JM, Lee EJ, Guyatt G (2009) Citrus fruit intake and pancreatic cancer risk: a quantitative systematic review. Pancreas 38:168–174CrossRefPubMedGoogle Scholar
  20. 20.
    Bae JM, Lee EJ, Guyatt G (2008) Citrus fruits intake and prostate cancer risk: a quantitative systematic review. J Prev Med Public Health 41:159–164CrossRefPubMedGoogle Scholar
  21. 21.
    Bravi F, Bosetti C, Scotti L et al (2007) Food groups and renal cell carcinoma: a case–control study from Italy. Int J Cancer 120:681–685CrossRefPubMedGoogle Scholar
  22. 22.
    Bosetti C, La Vecchia C, Talamini R et al (2000) Food groups and risk of squamous cell esophageal cancer in northern Italy. Int J Cancer 87:289–294CrossRefPubMedGoogle Scholar
  23. 23.
    Levi F, Pasche C, Lucchini F, Chatenoud L, Jacobs DR Jr, La Vecchia C (2000) Refined and whole grain cereals and the risk of oral, oesophageal and laryngeal cancer. Eur J Clin Nutr 54:487–489CrossRefPubMedGoogle Scholar
  24. 24.
    Lucenteforte E, Scita V, Bosetti C, Bertuccio P, Negri E, La Vecchia C (2008) Food groups and alcoholic beverages and the risk of stomach cancer: a case–control study in Italy. Nutr Cancer 60:577–584CrossRefPubMedGoogle Scholar
  25. 25.
    Franceschi S, Favero A, La Vecchia C et al (1997) Food groups and risk of colorectal cancer in Italy. Int J Cancer 72:56–61CrossRefPubMedGoogle Scholar
  26. 26.
    Franceschi S, Parpinel M, La Vecchia C, Favero A, Talamini R, Negri E (1998) Role of different types of vegetables and fruit in the prevention of cancer of the colon, rectum, and breast. Epidemiology 9:338–341PubMedCrossRefGoogle Scholar
  27. 27.
    Bosetti C, La Vecchia C, Talamini R et al (2002) Food groups and laryngeal cancer risk: a case–control study from Italy and Switzerland. Int J Cancer 100:355–360CrossRefPubMedGoogle Scholar
  28. 28.
    Franceschi S, Favero A, La Vecchia C et al (1995) Influence of food groups and food diversity on breast cancer risk in Italy. Int J Cancer 63:785–789CrossRefPubMedGoogle Scholar
  29. 29.
    Levi F, Pasche C, Lucchini F, La Vecchia C (2001) Dietary intake of selected micronutrients and breast cancer risk. Int J Cancer 91:260–263CrossRefPubMedGoogle Scholar
  30. 30.
    Lucenteforte E, Talamini R, Montella M et al (2008) Macronutrients, fatty acids and cholesterol intake and endometrial cancer. Ann Oncol 19:168–172CrossRefPubMedGoogle Scholar
  31. 31.
    Bosetti C, Negri E, Franceschi S et al (2001) Diet and ovarian cancer risk: a case–control study in Italy. Int J Cancer 93:911–915CrossRefPubMedGoogle Scholar
  32. 32.
    Bosetti C, Micelotta S, Dal Maso L et al (2004) Food groups and risk of prostate cancer in Italy. Int J Cancer 110:424–428CrossRefPubMedGoogle Scholar
  33. 33.
    Franceschi S, Favero A, Conti E et al (1999) Food groups, oils and butter, and cancer of the oral cavity and pharynx. Br J Cancer 80:614–620CrossRefPubMedGoogle Scholar
  34. 34.
    Ferraroni M, La Vecchia C, D’Avanzo B, Negri E, Franceschi S, Decarli A (1994) Selected micronutrient intake and the risk of colorectal cancer. Br J Cancer 70:1150–1155PubMedGoogle Scholar
  35. 35.
    La Vecchia C, D’Avanzo B, Negri E, Decarli A, Benichou J (1995) Attributable risks for stomach cancer in northern Italy. Int J Cancer 60:748–752CrossRefPubMedGoogle Scholar
  36. 36.
    Decarli A, Franceschi S, Ferraroni M et al (1996) Validation of a food-frequency questionnaire to assess dietary intakes in cancer studies in Italy. Results for specific nutrients. Ann Epidemiol 6:110–118CrossRefPubMedGoogle Scholar
  37. 37.
    Franceschi S, Negri E, Salvini S et al (1993) Reproducibility of an Italian food frequency questionnaire for cancer studies: results for specific food items. Eur J Cancer 29A:2298–2305CrossRefPubMedGoogle Scholar
  38. 38.
    Breslow NE, Day NE (1980) Statistical methods in cancer research. Volume I—The analysis of case–control studies. IARC Sci Publ 32:5–338PubMedGoogle Scholar
  39. 39.
    Lagiou P, Samoli E, Lagiou A et al (2004) Flavonoids, vitamin C and adenocarcinoma of the stomach. Cancer Causes Control 15:67–72CrossRefPubMedGoogle Scholar
  40. 40.
    Fountoulakis A, Martin IG, White KL et al (2004) Plasma and esophageal mucosal levels of vitamin C: role in the pathogenesis and neoplastic progression of Barrett’s esophagus. Dig Dis Sci 49:914–919CrossRefPubMedGoogle Scholar
  41. 41.
    De Stefani E, Ronco A, Mendilaharsu M, Deneo-Pellegrini H (1999) Diet and risk of cancer of the upper aerodigestive tract. II. Nutrients. Oral Oncol 35:22–26CrossRefPubMedGoogle Scholar
  42. 42.
    Rossi M, Garavello W, Talamini R et al (2007) Flavonoids and risk of squamous cell esophageal cancer. Int J Cancer 120:1560–1564CrossRefPubMedGoogle Scholar
  43. 43.
    Neuhouser ML (2004) Dietary flavonoids and cancer risk: evidence from human population studies. Nutr Cancer 50:1–7CrossRefPubMedGoogle Scholar
  44. 44.
    Hoensch HP, Kirch W (2005) Potential role of flavonoids in the prevention of intestinal neoplasia: a review of their mode of action and their clinical perspectives. Int J Gastrointest Cancer 35:187–195CrossRefPubMedGoogle Scholar
  45. 45.
    La Vecchia C, Chatenoud L, Franceschi S, Soler M, Parazzini F, Negri E (1999) Vegetables and fruit and human cancer: update of an Italian study. Int J Cancer 82:151–152CrossRefPubMedGoogle Scholar
  46. 46.
    D’Avanzo B, La Vecchia C, Katsouyanni K, Negri E, Trichopoulos D (1997) An assessment, and reproducibility of food frequency data provided by hospital controls. Eur J Cancer Prev 6:288–293CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Roberto Foschi
    • 1
  • Claudio Pelucchi
    • 1
    Email author
  • Luigino Dal Maso
    • 2
  • Marta Rossi
    • 1
  • Fabio Levi
    • 3
  • Renato Talamini
    • 2
  • Cristina Bosetti
    • 1
  • Eva Negri
    • 1
  • Diego Serraino
    • 2
  • Attilio Giacosa
    • 4
  • Silvia Franceschi
    • 5
  • Carlo La Vecchia
    • 1
    • 6
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri”MilanItaly
  2. 2.S.O.C. di Epidemiologia e BiostatisticaCentro di Riferimento OncologicoAvianoItaly
  3. 3.Unité d’Épidémiologie du Cancer et Registre Vaudois des Tumeurs, Institut de Medicine Sociale et Preventive (IUMSP)Centre Hospitalier Universitaire Vaudois et Université de LausanneLausanneSwitzerland
  4. 4.Department of Gastroenterology and Clinical NutritionPoliclinico di MonzaMonzaItaly
  5. 5.International Agency for Research on CancerLyon CedexFrance
  6. 6.Istituto di Statistica Medica e Biometria “G.A. Maccacaro”Università Degli Studi di MilanoMilanItaly

Personalised recommendations