Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Serum Phospholipid Fatty Acids in Benign Breast Tumor and Breast Cancer

양성 유방 종양과 유방암 환자의 혈청 인지질 지방산 조성

  • Shim, Eu-Gene (National Hypertension Center, Yonsei University Health System) ;
  • Ahn, Sei-Hyun (Department of Surgery, College of Medicine University of Ulsan, Asan Medical Center) ;
  • Hwang, You-Jeong (Research Institute of Food & Nutritional Sciences, Yonsei University) ;
  • Leekim, Yang-Cha (Research Institute of Food & Nutritional Sciences, Yonsei University)
  • 심유진 (연세대학교의료원 국민고혈압사업단) ;
  • 안세현 (울산대학교 의과대학 서울아산병원 외과학교실) ;
  • 황유정 (연세대학교 식품영양과학연구소) ;
  • 이양자 (연세대학교 식품영양과학연구소)
  • Published : 2009.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Studies on the relationship between blood fatty acids and the risk of breast cancer have not yielded definite conclusions. The role of fatty acids in the development and progression of breast cancer is unclear. We conducted a case-control study to determine serum phospholipid fatty acid composition in benign breast tumor and breast cancer. Subjects consisted of 27 benign breast tumor and 68 breast cancer patients, and 28 matched controls. The levels of fatty acids were measured by gas chromatography. Higher arachidonic and palmitic acids were observed in breast cancer patients as compared with control and benign breast tumor patients. The percentage of total saturated fatty acids in breast cancer was higher than in control and benign breast tumor patients. The level of stearic acid was lower in benign breast tumor and breast cancer patients. Saturation index, the ratio of stearic to oleic acid, was lower in benign breast tumor and breast cancer patients compared to the control. Moreover, stearic acid was negatively and arachidonic acid was positively correlated with the cancer stage. In conclusion, our results support that serum phospholipid compositions of specific fatty acids are associated with the risk of benign breast tumor as well as breast cancer. Further studies are necessary to investigate mechanisms linked to the breast cancer etiology.

본 연구에서는 유방암과 유방 양성종양 환자의 혈청 인지질 지방산 조성을 대조군과 비교, 분석하였으며, 유방암군을 병기에 따라 네 개의 군으로 분류하거나 림프절 전이 여부에 따라 두 군으로 나누어 혈청 인지질 지방산 조성에 차이가 있는지를 조사하였다. 그 결과를 요약하면 아래와 같다. 1) 출산 자녀수에서 양성 유방 종양과 유방암 환자군이 대조군에 비하여 유의하게 적었다. 2) 대조군과 양성 유방 종양환자에 비해 유방암 환자에서 ${\omega}$3계 PUFA인 혈청 인지질 DGLA와 AA의 수준이 높았으며 ${\omega}$3계 PUFA인 eicosatrienoic acid는 대조군에 비하여 양성 유방종양군과 유방암군에서 낮았으며, DPA는 대조군에 비하여 유방암 환자에서 낮은 수준이었다. 3) 총 SFA의 합은 대조군과 양성 유방종양 환자에 비하여 유방암 환자에서 높은 것으로 나타났다. Palmitic acid는 대조군과 양성 유방 종양 환자군에 비하여 유방암 환자군에서 높았으나, stearic acid는 대조군에 비하여 양성 유방 종양 환자군과 유방암 환자군에서 낮은 것이 특징적이었다. 4) SI로서 C18 : 0/C18 : 1 비율은 대조군에 비하여 양성 유방 종양 환자군과 유방암 환자군에서 낮았다. 5) AA 수준은 0기에 비하여 I, II, III기에서 높았으며, 림프절 전이 음성인 군과 양성인 군을 비교했을 때 양성인군에서 높은 것으로 나타났다. Stearic acid의 수준은 네개의 군 중에서 가장 낮은 수준의 병기인 0기와 가장 높은 수준의 병기인 III기 간에 유의한 차이가 있었으며 0기에 비하여 III기에서 stearic acid가 낮은 것으로 나타났다. 이상에서와 같이 혈청 인지질의 지방산 조성은 유방암 환자군에서 변화되어 있었으며 특히 양성 유방종양 단계에서 변화가 나타난 지방산도 있었다. 또한 AA와 stearic acid 등 일부 개별 지방산들은 유방암의 진행 단계와도 관련되어 있었다. 따라서 혈청 인지질의 지방산 조성은 유방암의 예방 뿐 아니라 진행의 단계에 따라 유의 깊게 관찰해야 할 중요한 요소로 사료된다.

Keywords

References

  1. Ministry for Health, Welfare and Family Affairs, Cancer Incidence in Korea 1999-2005. Seoul; 2005
  2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55(2): 74-108 https://doi.org/10.3322/canjclin.55.2.74
  3. Nelson NJ. Migrant studies aid the search for factors linked to breast cancer risk. J Natl Cancer Inst 2006; 98(7): 436-438 https://doi.org/10.1093/jnci/djj147
  4. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med 2008; 233(6): 674-688 https://doi.org/10.3181/0711-MR-311
  5. Chen YQ, Edwards IJ, Kridel SJ, Thornburg T, Berquin IM. Dietary fat-gene interactions in cancer. Cancer Metastasis Rev 2007; 26(3-4): 535-551 https://doi.org/10.1007/s10555-007-9075-x
  6. Berquin IM, Edwards IJ, Chen YQ. Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett 2008; 269(2): 363-377 https://doi.org/10.1016/j.canlet.2008.03.044
  7. Boyd NF, Stone J, Vogt KN, Connelly BS, Martin LJ, Minkin S. Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature. Br J Cancer 2003; 89(9): 1672-1685 https://doi.org/10.1038/sj.bjc.6601314
  8. Smith-Warner SA, Stampfer MJ. Fat intake and breast cancer revisited. J Natl Cancer Inst 2007; 99(6): 418-419 https://doi.org/10.1093/jnci/djk124
  9. Thiebaut AC, Kipnis V, Chang SC, Subar AF, Thompson FE, Rosenberg PS, Hollenbeck AR, Leitzmann M, Schatzkin A. Dietary fat and postmenopausal invasive breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort. J Natl Cancer Inst 2007; 99(6): 451-462 https://doi.org/10.1093/jnci/djk094
  10. Saadatian-Elahi M, Toniolo P, Ferrari P, Goudable J, Akhmedkhanov A, Zeleniuch-Jacquotte A, Riboli E. Serum fatty acids and risk of breast cancer in a nested case-control study of the New York University Women's Health Study. Cancer Epidemiol Biomarkers Prev 2002; 11(11): 1353-1360
  11. Riccardi G, Giacco R, Rivellese AA. Dietary fat, insulin sensitivity and the metabolic syndrome. Clin Nutr 2004; 23(4): 447-456 https://doi.org/10.1016/j.clnu.2004.02.006
  12. Scaglia N, Igal RA. Stearoyl-CoA desaturase is involved in the control of proliferation, anchorage-independent growth, and survival in human transformed cells. J Biol Chem 2005; 280(27): 25339-25349 https://doi.org/10.1074/jbc.M501159200
  13. Fermor BF, Masters JR, Wood CB, Miller J, Apostolov K, Habib NA. Fatty-acid composition of normal and malignant cells and cytotoxicity of stearic, oleic and sterculic acids in vitro. Eur J Cancer 1992; 28A(6-7): 1143-1147 https://doi.org/10.1016/0959-8049(92)90475-H
  14. Chajes V, Hulten K, Van Kappel AL, Winkvist A, Kaaks R, Hallmans G, Lenner P, Riboli E. Fatty-acid composition in serum phospholipids and risk of breast cancer: an incident case-control study in Sweden. Int J Cancer 1999; 83(5): 585-590 https://doi.org/10.1002/(SICI)1097-0215(19991126)83:5<585::AID-IJC2>3.0.CO;2-Z
  15. Pala V, Krogh V, Muti P, Chajès V, Riboli E, Micheli A, Saadatian M, Sieri S, Berrino F. Erythrocyte membrane fatty acids and subsequent breast cancer: a prospective Italian study. J Natl Cancer Inst 2001; 93(14): 1088-1095 https://doi.org/10.1093/jnci/93.14.1088
  16. Shannon J, King IB, Moshofsky R, Lampe JW, Gao DL, Ray RM, Thomas DB. Erythrocyte fatty acids and breast cancer risk: a case-control study in Shanghai, China. Am J Clin Nutr 2007; 85(4): 1090-1097
  17. Ma J, Folsom AR, Shahar E, Eckfeldt JH. Plasma fatty acid composition as an indicator of habitual dietary fat intake in middle- aged adults. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Am J Clin Nutr 1995; 62(3): 564-571
  18. Olveira G, Dorado A, Olveira C, Padilla A, Rojo-Martínez G, García-Escobar E, Gaspar I, Gonzalo M, Soriguer F. Serum phospholipid fatty acid profile and dietary intake in an adult Mediterranean population with cystic fibrosis. Br J Nutr 2006; 96(2): 343-349 https://doi.org/10.1079/BJN20051655
  19. Russo J, Moral R, Balogh GA, Mailo D, Russo IH. The protective role of pregnancy in breast cancer. Breast Cancer Res 2005; 7(3): 131-142 https://doi.org/10.1186/bcr1029
  20. Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A. Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 2004; 79(6): 935-945
  21. Terry PD, Rohan TE, Wolk A. Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence. Am J Clin Nutr 2003; 77(3): 532-543
  22. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC. Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA 2006; 295(4): 403-415 https://doi.org/10.1001/jama.295.4.403
  23. Kuriki K, Hirose K, Wakai K, Matsuo K, Ito H, Suzuki T, Hiraki A, Saito T, Iwata H, Tatematsu M, Tajima K. Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese. Int J Cancer 2007; 121(2): 377-385 https://doi.org/10.1002/ijc.22682
  24. Chajés V, Lanson M, Fetissof F, Lhuillery C, Bougnoux P. Membrane fatty acids of breast carcinoma: contribution of host fatty acids and tumor properties. Int J Cancer 1995; 63(2): 169-175 https://doi.org/10.1002/ijc.2910630204
  25. Pockaj BA, Basu GD, Pathangey LB, Gray RJ, Hernandez JL, Gendler SJ, Mukherjee P. Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer. Ann Surg Oncol 2004; 11(3): 328-339 https://doi.org/10.1245/ASO.2004.05.027
  26. Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY. Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem 2006; 52(12): 2265-2272 https://doi.org/10.1373/clinchem.2006.072322
  27. de Alaniz MJ, Marra CA. Steroid hormones and fatty acid desaturases. Prostaglandins Leukot Essent Fatty Acids 2003; 68(2): 163-170 https://doi.org/10.1016/S0952-3278(02)00266-1
  28. Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, Vierkant RA, Maloney SD, Pankratz VS, Hillman DW, Suman VJ, Johnson J, Blake C, Tlsty T, Vachon CM, Melton LJ 3rd, Visscher DW. Benign breast disease and the risk of breast cancer. N Engl J Med 2005; 353(3): 229-237 https://doi.org/10.1056/NEJMoa044383
  29. Wang J, Costantino JP, Tan-Chiu E, Wickerham DL, Paik S, Wolmark N. Lower-category benign breast disease and the risk of invasive breast cancer. J Natl Cancer Inst 2004; 96(8): 616-620 https://doi.org/10.1093/jnci/djhs105
  30. Liu H, Liu Y, Zhang JT. A new mechanism of drug resistance in breast cancer cells: fatty acid synthase overexpression-mediated palmitate overproduction. Mol Cancer Ther 2008; 7(2): 263-270 https://doi.org/10.1158/1535-7163.MCT-07-0445
  31. Marra CA, Mangionil JO, Tavella M, del Alaniz MJ, Ortiz D, Sala C. Hormonal-induced changes on the lipid composition and DPH fluorescence anisotropy of erythrocyte ghost from pre- and postmenopausal women. Acta Physiol Pharmacol Ther Latinoam 1998; 48(1): 8-17
  32. Choi Y, Park Y, Storkson JM, Pariza MW, Ntambi JM. Inhibition of stearoyl-CoA desaturase activity by the cis-9, trans-11 isomer and the trans-10, cis-12 isomer of conjugated linoleic acid in MDA-MB-231 and MCF-7 human breast cancer cells. Biochem Biophys Res Commun 2002; 294(4): 785-790 https://doi.org/10.1016/S0006-291X(02)00554-5
  33. Wood CB, Habib NA, Thompson A, Bradpiece H, Smadja C, Hershman M, Barker W, Apostolov K. Increase of oleic acid in erythrocytes associated with malignancies. Br Med J 1985; 291 (6489): 163-165 https://doi.org/10.1136/bmj.291.6489.163
  34. Mannello F, Qin W, Zhu W, Fabbri L, Tonti GA, Sauter ER. Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2. Breast Cancer Res Treat 2008; 111(2): 209-218 https://doi.org/10.1007/s10549-007-9779-1
  35. Wang J, John EM, Ingles SA. 5-lipoxygenase and 5-lipoxygenase- activating protein gene polymorphisms, dietary linoleic acid, and risk for breast cancer. Cancer Epidemiol Biomarkers Prev 2008; 17(10): 2748-2754 https://doi.org/10.1158/1055-9965.EPI-08-0439
  36. Le Floch O. Prognostic significance of tumor phosphatidylcholine stearic acid level in breast carcinoma. Breast Cancer Res Treat 1991; 20(3): 185-194 https://doi.org/10.1007/BF01834624