Explaining Cancer Incidence in the Jejudo Population
Jong-Myon Bae
Department of Preventive Medicine, Cheju National University College of Medicine, Jejudo, Republic of Korea Objectives : Using the population-based cancer registry
in Jejudo, we found that Jejudo had lower incidence in stomach cancer than other regions in Korea. The aim of this study was to evaluate reasons for this difference.
Methods : Citrus is the leading agricultural production in Jejudo, suggesting that lower cancer incidence in Jejudo could be explained by citrus fruit intake. We evaluated this hypothesis with quantitative systematic review (QSR).
Results : Stomach cancer incidence was significantly lower, with a summary odds ratio (SOR) after QSR of 0.72 [95% CI=0.64-0.81]. In addition, the SOR of pancreatic cancer tended to be lower at 0.83 [95% CI=0.70-0.98]. The
SOR of prostate cancer was slightly higher at 1.03 [0.89- 1.19].
Conclusions : Quantitative systematic reviews for the effect of citrus fruit intake on cancer occurrence suggested that lower cancer incidence in Jejudo could be explained by intake of citrus fruits.
J Prev Med Public Health 2009;42(1):67-72
Key words : Citrus, Incidence, Neoplasm, Pancreas, Prostate, Stomach
(population-based regional cancer registry)
- , , -
,
[1].
[2], .
2001
2008
[3]. 2000-2002 2007
(International Agency of Cancer
Research: IARC)
(Cancer incidence in 5 continents: CI5) 9 [4]
, 7
[5]. 8
Table 1,2
. 95%
(CI) 7
,
(All) (C16)
. .
, 1
. ,
[6].
, 2001
1 1
[7].
Helicobacter pylori (H. pylori) 174
[8]. H.pylori
,
.
.
Table 1 2 .
(carcino- genesis)
, (somatic
mutations)
[9],
. [10-14]
[15-17], carotenoids
A [18], DNA
[19-26].
bata-carotene
[27], bata-carotene
1980 [28-32].
, beta-carotene
, beta-carotene
[11,33,34].
1994 The Alpha-
Tocopherol, Beta Carotene Cancer Prevention
Study (ATBC) , 50-69
beta-carotene
[34]. 2 Physician s
Health Study (PHS) 40-84
beta-carotene
[35].
The Beta Carotene and Retinol Efficacy Trial (CARET)
2001 2005
[7]
.
.
( )
(case series study), (cross-sectional study)
(descriptive epidemiological study)
, -
(cross-sectional study),
(cohort study) (analytic
epidemiological study) .
(clinical trial),
(community trial) (interven-
tional study) ,
[47].
, Table 1 Table 2
,
- , -
- , -
. , (unknown intervention factor)
.
. beta-carotene
[36].
beta-carotene
[37], ATBC CARET
1994 1996
[38,39].
ATBC
beta-carotene alpha-tocopherol [40]. 2004
(systematic review) [41], 2006
[42].
beta-carotene , 2001 Arab [43]
. 2003 ATBC
-
lutein, zeaxanthin, beta-cryptoxanthin
[44].
2004 7
(raw data)
(pooled analy-
sis) beta-cryptoxanthin
[45].
beta-cryptoxanthin
carotenoid , (citrus
fruits) [18].
1 ,
[46].
.
lycopene [55].
. 2007 8
11 [56].
OR
RR 95%
random-effect .
,
.
(Table 1).
, ATBC 1994 1998
, 50-69 alpha-tocophenol
[34,51]. 1999
PHS beta-carotene
[52]. 2000 -
alpha-tocopherol, gamma-tocopherol,
selenium 3 2
[53].
2005 vitamin C/E
PSA
[54] , 2006
, .
( )
(meta-analysis)
(qualitative systematic review) .
(bias) (random
error) ,
[48,49].
,
(expert
overview) (Table 3).
2000-2002
.
. 2007 4
14 [50].
OR
RR 95%
fixed-effect model .
(summary odds ratio) 0.72 [95% CI=
0.64-0.81] .
. Helcobacter pylori
Table 1. Comparison of age-standardized incidence rates (per 100,000) in men among 8 population- based regional cancer registries in Korea*
Site (ICD-10) Jejudo (95% CI) Busan Daegu Daejeon Gwangju Incheon Seoul Ulsan All
Stomach (C16) Lung (C33-34) Liver (C22) Prostate (C61) Colon (C18) Gallbladder (C23-24) Esophagus (C15) Bladder (C67) Larynx (C32) Pancreas (C25)
* Modified from Curado MP, et al. [4]
256.8 (244.6- 268.4) 054.3 (49.0- 59.7) 045.0 (39.8- 50.2) 044.4 (39.6- 49.1) 011.8 (9.0- 14.5) 011.2 (8.7- 13.6) 008.5 (6.2- 10.7) 007.2 (5.2- 9.2) 006.8 (4.8- 8.7) 006.3 (4.5- 8.1) 005.0 (3.3- 6.7)
273.7 59.9 46.2 49.8 7.3 12.7 9.3 8.1 10.2 4.8 7.7
293.2 69.2 52.8 46.1 7.7 13.5 10.4 8.1 9.2 5.1 7.3
277.3 73.8 46.3 35.4 5.8 16.7 7.0 6.0 10.1 4.6 7.9
301.3 66.6 51.4 50.2 9.0 14.6 10.0 10.6 10.2 5.0 8.3
267.6 62.4 50.2 36.7 7.8 15.5 7.1 6.3 8.9 4.4 7.8
298.3 63.7 49.7 44.1 12.7 18.7 8.0 7.1 11.0 4.7 8.7
288.2 67.4 57.6 42.7 8.6 14.8 10.1 7.9 8.5 5.4 8.7
Table 2. Comparison of age-standardized incidence rates (per 100,000) in women among 8 population-based regional cancer registries in Korea*
Site (ICD-10) Jejudo (95% CI) Busan Daegu Daejeon Gwangju Incheon Seoul Ulsan All (C00-96)
Stomach (C16) Breast (C50) Cervix Uteri (C53) Thyroid (C73) Liver (C22) Lung (C33-34) Gallbladder (C23-24) Colon (C18) Pancreas (C25) Bladder (C67) Larynx (C32)
*Modified from Curado MP, et al. [4]
144.9 (137.2- 152.3) 019.8 (17.1- 22.4) 016.6 (14.0- 19.2) 013.8 (11.4- 16.1) 013.1 (10.8- 15.4) 012.0 (9.9- 14.2) 010.7 (8.7- 12.7) 008.0 (6.3- 9.6) 006.9 (5.3- 8.5) 003.6 (2.5- 4.8) 001.1 (0.5- 1.7) 000.8 (0.2- 1.4)
158.2 23.9 21.2 15.3 8.5 14.9 12.2 7.4 7.8 3.8 1.7 0.6
175.9 28.8 24.9 16.0 10.1 12.9 13.6 7.5 9.1 4.4 2.1 0.4
168.4 29.1 25.2 18.6 8.8 10.3 11.7 4.8 8.8 4.5 2.0 0.4
175.6 27.5 21.2 14.5 21.4 10.8 13.3 5.8 8.9 4.4 2.1 0.3
167.6 22.5 25.0 19.8 10.3 11.7 13.0 5.0 9.8 3.8 1.6 0.5
190.7 27.1 28.8 17.8 14.1 13.0 14.4 6.3 11.5 5.0 2.1 0.4
165.4 26.8 21.3 14.2 12.3 11.0 13.9 7.0 9.9 4.6 1.4 0.3
Table 3. Comparison between expert overview and systematic review
Expert overview Systematic review Protocol
Searching Selection Criteria Appraisal Criteria Repeatability Summary
No or Yes Haphazard Undefined Unfixed No or Yes Tables
Should Comprehensive Defined Fixed Should Forest Plot
model .
1.03 [95% CI=0.89, 1.19]
.
(sensitivity analysis) (subgroup analysis)
.
.
(Table 1),
(Table 2).
.
30-50%
[57], C
[58-61]. C E
[62].
. 2007 12
9 [63].
,
OR
RR 95%
.
(subgroup
analysis) -
,
. random-effect
model ,
0.83 [95% CI=0.70-0.98]
.
.
.
. 1994 American Journal of Epidemiology Shapiro
[64,65], Petitti [66] Greenland [67]
.
1998 Egger
,
,
[68].
, ,
, .
1. Hiatt RA, Rimer BK. A new strategy for cancer control research. Cancer Epidemiol Biomarkers Prev 1999; 8(11): 957-964.
2. Kabuto M, Nitta H, Yamamoto S, Yamaguchi N, Akiba S, Honda Y, et al. Childhood leukemia and magnetic fields in Japan: A case-control study of childhood leukemia and residential power-frequency magnetic fields in Japan. Int J Cancer 2006; 119(3): 643-650.
3. Yang YJ, Bae JM. Survival rates of the 5 major cancers in Jeju Island residents, 2000-2001. J Prev Med Public Health 2007; 40(3): 213-217.
(Korean)
4. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, et al, editors. Cancer incidence in five continents, vol. IX. IARC
Scientific Publication No. 160. Lyon: IARC;
2007.
5. The community of population-based regional cancer registries in Korea: An estimation of the national cancer incidence in Korea for 2000- 2002 using the databases of 8 population-based regional cancer registries. J Prev Med Public Health 2008; 41(6): 380-386. (Korean) 6. DeVita VT, Hellman S, Rosenberg SA. Cancer:
Principles and Practice of Oncology. 7th ed.
Philadelphia: Lippincott Williams & Wilkins;
2005. p.910.
7. Korea Health Industry Development Institute.
2001 Report of Korea National Health and Nutrition Survey. [cited 2008 Dec 10]. Available from: URL:http://knhanes.cdc.go.kr. (Korean) 8. Yim JY, Kim N, Choi SH, Kim YS, Cho KR,
Kim SS, et al. Seroprevalence of Helicobacter pylori in South Korea. Helicobacter 2007;
12(4): 333-340.
9. Stewart BW, Kleihues P. World Cancer Report.
Lyon: WHO IARC Press; 2003. p.83-88.
10. Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 1975; 15(4): 617-631.
11. Ziegler RG. A review of epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr 1989; 119(1): 116-122.
12. Mayne ST, Graham S, Zheng TZ. Dietary retinol: Prevention or promotion of carcino- genesis in humans? Cancer Causes Control 1991; 2(6): 443-450.
13. Byers T, Perry G. Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. Annu Rev Nutr 1992; 12: 139- 159.
14. van Popple G. Carotenoids and cancer: An update with emphasis on human intervention studies. Eur J Cancer 1993; 29A(9): 1335- 1344.
15. Steinmetz KA, Potter JD. Vegetables, fruit, and cancer: I. Epidemiology. Cancer Causes Control 1991; 2(5): 325-357.
16. Block G, Patterson B, Subar A. Fruit, vegetables, and cancer prevention: A review of the epidemiological evidence. Nutr Cancer 1992; 18(1): 1-29.
17. Choices for good health: American cancer society guidelines for nutrition and physical activity for cancer prevention. CA Cancer J Clin 2006; 56(5): 310-312.
18. Chug-Ahuja JK, Holden JM, Forman MR, Mangels AR, Beecher GR, Lanza E. The development and application of a carotenoid database for fruits, vegetables, and selected multicomponent foods. J Am Diet Assoc 1993;
93(3): 318-323.
19. Di Mascio P, Kaiser S, Sies H. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys 1989; 274(2): 532-538.
20. Di Mascio P, Murphy ME, Sies H. Antioxidant defense systems: The role of carotenoids, tocopherols, and thiols. Am J Clin Nutr 1991;
53(1 Suppl): 194S-200S.
21. Halliwell B, Gutteridge JM, Cross CE. Free radicals, antioxidants, and human disease:
Where are we now? J Lab Clin Med 1992;
119(6): 598-620.
22. Ames BN, Shigenaga MK, Hagen TM.
Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993; 90(17): 7915-7922.
23. Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: Role in inflammatory disease and progression to cancer. Biochem J 1996; 313(Pt 1): 17-29.
24. Palozza P. Prooxidant actions of carotenoids in biologic systems. Nutr Rev 1998; 56(9): 257- 265.
25. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 2007; 121(11): 2381-2386.
26. World Cancer Research Fund, American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington DC: American Institute for Cancer Research;
2007. p.37-46.
27. Campbell DR, Gross MD, Martini MC, Grandits GA, Slavin JL, Potter JD. Plasma carotenoids as biomarkers of vegetable and fruit intake. Cancer Epidemiol Biomarkers Prev 1994; 3(6): 493-500.
28. Peto R, Doll R, Buckley JD, Sporn MB. Can dietary beta-carotene materially reduce human cancer rates? Nature 1981; 290(5803): 201- 208.
29. Colditz GA, Branch LG, Lipnick RJ, Willett WC, Rosner B, Posner BM, Hennekens CH.
Increased green and yellow vegetable intake and lowered cancer deaths in an elderly population. Am J Clin Nutr 1985; 41(1): 32-36.
30. Stähelin HB, Gey KF, Eichholzer M, Lüdin E, Brubacher G. Cancer mortality and vitamin E status. Ann N Y Acad Sci 1989; 570: 391-399.
31. Steinmetz KA, Potter JD. Vegetables, fruits and cancer: II. Mechanisms. Cancer Causes Control 1991; 2(6): 427-442.
32. Wang XD, Russell RM. Procarcinogenic and anticarcinogenic effects of beta-carotene. Nutr Rev 1999; 57(9 Pt 1): 263-272.
33. Knekt P, Järvinen R, Seppänen R, Rissanen A, Aromaa A, Heinonen OP, et al. Dietary
antioxidants and the risk of lung cancer. Am J Epidemiol 1991; 134(5): 471-479.
34. van Poppel G, Goldbohm RA. Epidemiologic evidence for beta-carotene and cancer prevention. Am J Clin Nutr 1995; 62(6 Suppl):
1393S-1402S.
35. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996; 334(18): 1145-1149.
36. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996; 334(18): 1150-1155.
37. Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. Beta-carotene supplemen- tation and incidence of cancer and cardiovas- cular disease: The Women s Health Study. J Natl Cancer Inst 1999; 91(24): 2102-2106.
38. Virtamo J, Pietinen P, Huttunen JK, Korhonen P, Malila N, Virtanen MJ, et al. Incidence of cancer and mortality following alpha- tocopherol and beta-carotene supple- mentation: A postintervention follow-up.
JAMA 2003; 290(4): 476-485.
39. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL Jr, Omenn GS, et al.
The beta-carotene and retinol efficacy trial:
Incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supple- ments. J Natl Cancer Inst 2004; 96(23): 1743- 1750.
40. Malila N, Taylor PR, Virtanen MJ, Korhonen P, Huttunen JK, Albanes D, et al. Effects of alpha-tocopherol and beta-carotene supple- mentation on gastric cancer incidence in male smokers (ATBC study, Finland). Cancer Causes Control 2002; 13(7): 617-623.
41. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: A systematic review and meta-analysis. Lancet 2004; 364(9441): 1219-1228.
42. Davies AA, Davey Smith G, Harbord R, Bekkering GE, Sterne JA, Beynon R, et al.
Nutritional interventions and outcome in patients with cancer or preinvasive lesions:
Systematic review. J Natl Cancer Inst 2006;
98(14): 961-973.
43. Arab L, Steck-Scott S, Bowen P. Participation of lycopene and beta-carotene in carcino- genesis: Defenders, aggressors, or passive bystanders? Epidemiol Rev 2001; 23(2): 211- 230.
44. Goodman GE, Schaffer S, Omenn GS, Chen C, King I. The association between lung and prostate cancer risk, and serum micronutrients:
Results and lessons learned from beta-carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev 2003; 12(6): 518-526.
45. Männistö S, Smith-Warner SA, Spiegelman D, Albanes D, Anderson K, van den Brandt PA, et al. Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Cancer Epidemiol Biomarkers Prev 2004; 13(1): 40-48.
46. Ministry of Agriculture & Forestry, Republic of Korea. Agricultural & Forestry Statistical Yearbook 2007. [cited 2008 Dec 10]. Availa- ble from: URL: http://ebook.maf.go.kr.
(Korean)
47. Ahn YO, Yoo KY, Park BJ, Kim DH, Bae JM, Kang DH, et al. Epidemiology: The Principles and Applications. Seoul: Seoul National University Press; 2005. p.232-247.
(Korean)
48. Mulrow CD. Rationale for systematic reviews.
BMJ 1994; 309(6954): 597-599.
49. Flather MD, Farkouh ME, Pogue JM, Yusuf S.
Strengths and limitations of meta-analysis:
Larger studies may be more reliable. Control Clin Trials 1997; 18(6): 568-579.
50. Bae JM, Lee EJ, Guyatt G. Citrus fruit intake and stomach cancer risk: A quantitative systematic review. Gastric Cancer 2008;
11(1): 23-32.
51. Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, et al. Prostate cancer and supplementation with alpha- tocopherol and beta-carotene: Incidence and mortality in a controlled trial. J Natl Cancer Inst 1998; 90(6): 440-446.
52. Cook NR, Stampfer MJ, Ma J, Manson JE, Sacks FM, Buring JE, et al. Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma. Cancer 1999; 86(9): 1783-1792.
53. Helzlsouer KJ, Huang HY, Alberg AJ, Hoffman S, Burke A, Norkus EP, et al.
Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst 2000;
92(24): 2018-2023.
54. Hoenjet KM, Dagnelie PC, Delaere KP, Wijckmans NE, Zambon JV, Oosterhof GO.
Effect of a nutritional supplement containing vitamin E, selenium, vitamin c and coenzyme Q10 on serum PSA in patients with hormonally untreated carcinoma of the prostate: A randomised placebo-controlled study. Eur Urol 2005; 47(4): 433-439.
55. Kirsh VA, Mayne ST, Peters U, Chatterjee N,
Leitzmann MF, Dixon LB, et al. A prospective study of lycopene and tomato product intake and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2006; 15(1): 92-98.
56. Bae JM, Lee EJ, Guyatt G. Citrus fruit intake and prostate cancer risk: A quantitative systematic review. J Prev Med Public Health 2008; 41(3): 159-164.
57. World Cancer Research Fund in association with the American Institute of Cancer Research. Food, Nutrition, and Cancer Prevention: A Global Perspective. Washington DC: American Institute of Cancer Research;
1997.
58. Howe GR, Jain M, Miller AB. Dietary factors and risk of pancreatic cancer: Results of a Canadian population-based case-control study.
Int J Cancer 1990; 45(4): 604-608.
59. Ghadirian P, Boyle P, Simard A, Baillargeon J,
Maisonneuve P, Perret C. Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada.
Int J Pancreatol 1991; 10(3-4): 183-196.
60. Kalapothaki V, Tzonou A, Hsieh CC, Karakatsani A, Trichopoulou A, Toupadaki N, et al. Nutrient intake and cancer of the pancreas: A case-control study in Athens, Greece. Cancer Causes Control 1993; 4(4):
383-389.
61. Howe GR, Burch JD. Nutrition and pancreatic cancer. Cancer Causes Control 1996; 7(1): 69- 82.
62. Coulter ID, Hardy ML, Morton SC, Hilton LG, Tu W, Valentine D, et al. Antioxidants vitamin C and vitamin E for the prevention and treatment of cancer. J Gen Intern Med 2006;
21(7): 735-744.
63. Bae JM, Lee EJ, Guyatt G. Citrus fruit intake and pancreatic cancer risk: A quantitative systematic review. Pancreas 2008 Sep 26.
[Epub ahead of print]
64. Shapiro S. Meta-analysis/Shmeta-analysis. Am J Epidemiol 1994; 140(9): 771-778.
65. Shapiro S. Is there is or is there ain t no baby?
Dr. Shapiro replies to Drs. Petitti and Greenland. Am J Epidemiol 1994; 140(9): 788- 791.
66. Petitti DB. Of babies and bathwater. Am J Epidemiol 1994; 140(9): 779-782.
67. Greenland S. Can meta-analysis be salvaged?
Am J Epidemiol 1994; 140(9): 783-787.
68. Egger M, Schneider M, Davey Smith G.
Spurious precision? Meta-analysis of observational studies. BMJ 1998; 316(7125):
140-144.
