Skip to main content

Advertisement

SpringerLink
Log in

Fish consumption and n-3 polyunsaturated fatty acids, and risk of hepatocellular carcinoma: systematic review and meta-analysis

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

To investigate the association between fish consumption and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of hepatocellular carcinoma (HCC).

Methods

We identified eligible studies in MEDLINE and EMBASE up to July 2014 and the reference lists of original studies and review articles on this topic. Summary relative risks (SRR) with their 95 % confidence intervals (CI) were calculated with a random effects model.

Results

Eleven studies (three cohort studies, seven retrospective case–control studies, and one nested case–control study) met eligibility criteria. Ten articles investigated fish consumption, two articles investigated n-3 PUFA, and two articles investigated alpha-linolenic acid (ALA). The current data suggest that fish consumption was associated with 35 % reduction in HCC risk (highest vs. lowest category SRRs = 0.65, 95 % CI 0.51–0.79; test for heterogeneity p = 0.057, I 2 = 44.1 %). n-3 PUFA was associated with 51 % reduction in HCC risk (highest vs. lowest category SRRs = 0.49, 95 % CI 0.19–0.79). However, no significant inverse association was found in ALA (SRRs = 0.70, 95 % CI 0.30–1.10).

Conclusion

Our meta-analysis of observational studies provides evidence that fish consumption and n-3 PUFA has inverse association with the risk of HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

BMI:

Body mass index

DM:

Diabetes mellitus

PUFA:

Polyunsaturated fatty acids

ALA:

Alpha-linolenic acid

EPA:

Eicosapentaenoic acid

DPA:

Docosapentaenoic acid

DHA:

Docosahexaenoic acid

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107

    Article  PubMed  Google Scholar 

  2. Beasley RP (1988) Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61(10):1942–1956

    Article  CAS  PubMed  Google Scholar 

  3. Shiratori Y, Shiina S, Imamura M, Kato N, Kanai F, Okudaira T, Teratani T, Tohgo G, Toda N, Ohashi M, Et A (1995) Characteristic difference of hepatocellular carcinoma between hepatitis B- and C-viral infection in Japan. Hepatology 22(4 Pt 1):1027–1033

    Article  CAS  PubMed  Google Scholar 

  4. Altekruse SF, McGlynn KA, Reichman ME (2009) Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27(9):1485–1491. doi:10.1200/JCO.2008.20.7753

    Article  PubMed Central  PubMed  Google Scholar 

  5. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557–2576. doi:10.1053/j.gastro.2007.04.061

    Article  CAS  PubMed  Google Scholar 

  6. Purohit V, Rapaka R, Kwon OS, Song BJ (2013) Roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma. Life Sci 92(1):3–9. doi:10.1016/j.lfs.2012.10.009

    Article  CAS  PubMed  Google Scholar 

  7. Montella M, Polesel J, La Vecchia C, Dal Maso L, Crispo A, Crovatto M, Casarin P, Izzo F, Tommasi LG, Talamini R, Franceschi S (2007) Coffee and tea consumption and risk of hepatocellular carcinoma in Italy. Int J Cancer 120(7):1555–1559. doi:10.1002/ijc.22509

    Article  CAS  PubMed  Google Scholar 

  8. Kew MC (2014) Hepatic iron overload and hepatocellular carcinoma. Liver Cancer 3(1):31–40. doi:10.1159/000343856

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Fedirko V, Trichopolou A, Bamia C, Duarte-Salles T, Trepo E, Aleksandrova K, Nothlings U, Lukanova A, Lagiou P, Boffetta P, Trichopoulos D, Katzke VA, Overvad K, Tjonneland A, Hansen L, Boutron-Ruault MC, Fagherazzi G, Bastide N, Panico S, Grioni S, Vineis P, Palli D, Tumino R, Bueno-de-Mesquita HB, Peeters PH, Skeie G, Engeset D, Parr CL, Jakszyn P, Sanchez MJ, Barricarte A, Amiano P, Chirlaque M, Quiros JR, Sund M, Werner M, Sonestedt E, Ericson U, Key TJ, Khaw KT, Ferrari P, Romieu I, Riboli E, Jenab M (2013) Consumption of fish and meats and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition (EPIC). Ann Oncol 24(8):2166–2173. doi:10.1093/annonc/mdt168

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Bettinger D, Schultheiss M, Hennecke N, Panther E, Knuppel E, Blum HE, Thimme R, Spangenberg HC (2013) Selenium levels in patients with hepatitis C virus-related chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma: a pilot study. Hepatology 57(6):2543–2544. doi:10.1002/hep.26142

    Article  CAS  PubMed  Google Scholar 

  11. Fedirko V, Duarte-Salles T, Bamia C, Trichopoulou A, Aleksandrova K, Trichopoulos D, Trepo E, Tjonneland A, Olsen A, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Kvaskoff M, Kuhn T, Lukanova A, Boeing H, Buijsse B, Klinaki E, Tsimakidi C, Naccarati A, Tagliabue G, Panico S, Tumino R, Palli D, Bueno-de-Mesquita HB, Siersema PD, Peters PH, Lund E, Brustad M, Standahl OK, Weiderpass VE, Zamora R, Sanchez MJ, Ardanaz E, Amiano P, Navarro C, Quiros JR, Werner M, Sund M, Lindkvist B, Malm J, Travis RC, Khaw KT, Stepien M, Scalbert A, Romieu I, Lagiou P, Riboli E, Jenab M (2014) Pre-diagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case–control study. Hepatology. doi:10.1002/hep.27079

    PubMed Central  Google Scholar 

  12. Fernandez E, Chatenoud L, La Vecchia C, Negri E, Franceschi S (1999) Fish consumption and cancer risk. Am J Clin Nutr 70(1):85–90

    CAS  PubMed  Google Scholar 

  13. Rose DP, Connolly JM (1999) Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 83(3):217–244

    Article  CAS  PubMed  Google Scholar 

  14. Wu S, Feng B, Li K, Zhu X, Liang S, Liu X, Han S, Wang B, Wu K, Miao D, Liang J, Fan D (2012) Fish consumption and colorectal cancer risk in humans: a systematic review and meta-analysis. Am J Med 125(6):551–559. doi:10.1016/j.amjmed.2012.01.022

    Article  PubMed  Google Scholar 

  15. Song J, Su H, Wang BL, Zhou YY, Guo LL (2014) Fish consumption and lung cancer risk: systematic review and meta-analysis. Nutr Cancer 66(4):539–549. doi:10.1080/01635581.2014.894102

    Article  CAS  PubMed  Google Scholar 

  16. Szymanski KM, Wheeler DC, Mucci LA (2010) Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr 92(5):1223–1233. doi:10.3945/ajcn.2010.29530

    Article  CAS  PubMed  Google Scholar 

  17. Zheng JS, Hu XJ, Zhao YM, Yang J, Li D (2013) Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ 346:f3706

    Article  PubMed  Google Scholar 

  18. Wu S, Liang J, Zhang L, Zhu X, Liu X, Miao D (2011) Fish consumption and the risk of gastric cancer: systematic review and meta-analysis. BMC Cancer 11:26. doi:10.1186/1471-2407-11-26

    Article  PubMed Central  PubMed  Google Scholar 

  19. Jiang PY, Jiang ZB, Shen KX, Yue Y (2014) Fish intake and ovarian cancer risk: a meta-analysis of 15 case–control and cohort studies. PLoS One 9(4):e94601. doi:10.1371/journal.pone.0094601

    Article  PubMed Central  PubMed  Google Scholar 

  20. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283(15):2008–2012

    Article  CAS  PubMed  Google Scholar 

  21. La Vecchia C, Negri E, Decarli A, D’Avanzo B, Franceschi S (1988) Risk factors for hepatocellular carcinoma in northern Italy. Int J Cancer 42(6):872–876

    Article  PubMed  Google Scholar 

  22. Kurozawa Y, Ogimoto I, Shibata A, Nose T, Yoshimura T, Suzuki H, Sakata R, Fujita Y, Ichikawa S, Iwai N, Fukuda K, Tamakoshi A (2004) Dietary habits and risk of death due to hepatocellular carcinoma in a large scale cohort study in Japan. Univariate analysis of JACC study data. Kurume Med J 51(2):141–149

    Article  PubMed  Google Scholar 

  23. Greenland S (1987) Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 9:1–30

    CAS  PubMed  Google Scholar 

  24. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. doi:10.1002/sim.1186

    Article  PubMed  Google Scholar 

  25. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  PubMed Central  PubMed  Google Scholar 

  26. Sterne JA, Egger M (2001) Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 54(10):1046–1055

    Article  CAS  PubMed  Google Scholar 

  27. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463

    Article  CAS  PubMed  Google Scholar 

  28. Lu SN, Lin TM, Chen CJ, Chen JS, Liaw YF, Chang WY, Hsu ST (1988) A case–control study of primary hepatocellular carcinoma in Taiwan. Cancer 62(9):2051–2055

    Article  CAS  PubMed  Google Scholar 

  29. Qiu XQ, Tan SK, Yu HP, Zeng XY, Li LQ, Hu L (2008) Synergistic effect of HBV infection, alcohol and raw fish consumption on oncogenisis of primary hepatic carcinoma. Zhonghua Zhong Liu Za Zhi 30(2):113–115

    PubMed  Google Scholar 

  30. Tan SK, Qiu XQ, Yu HP, Zeng XY, Xiao ZM, Hu L (2008) Etiologic fraction and interaction of risk factors for primary hepatic carcinoma in Guangxi, China. Zhonghua Yu Fang Yi Xue Za Zhi 42(3):169–172

    PubMed  Google Scholar 

  31. Kuper H, Tzonou A, Lagiou P, Mucci LA, Trichopoulos D, Stuver SO, Trichopoulou A (2000) Diet and hepatocellular carcinoma: a case–control study in Greece. Nutr Cancer 38(1):6–12. doi:10.1207/S15327914NC381_2

    Article  CAS  PubMed  Google Scholar 

  32. Sawada N, Inoue M, Iwasaki M, Sasazuki S, Shimazu T, Yamaji T, Takachi R, Tanaka Y, Mizokami M, Tsugane S (2012) Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology 142(7):1468–1475. doi:10.1053/j.gastro.2012.02.018

    Article  CAS  PubMed  Google Scholar 

  33. Daniel CR, Cross AJ, Graubard BI, Hollenbeck AR, Park Y, Sinha R (2011) Prospective investigation of poultry and fish intake in relation to cancer risk. Cancer Prev Res (Phila) 4(11):1903–1911. doi:10.1158/1940-6207.CAPR-11-0241

    Article  Google Scholar 

  34. Wang MP, Thomas GN, Ho SY, Lai HK, Mak KH, Lam TH (2011) Fish consumption and mortality in Hong Kong Chinese–the LIMOR study. Ann Epidemiol 21(3):164–169. doi:10.1016/j.annepidem.2010.10.010

    Article  CAS  PubMed  Google Scholar 

  35. Kanazir M, Boricic I, Delic D, Tepavcevic DK, Knezevic A, Jovanovic T, Pekmezovic T (2010) Risk factors for hepatocellular carcinoma: a case–control study in Belgrade (Serbia). Tumori 96(6):911–917

    PubMed  Google Scholar 

  36. Polesel J, Talamini R, Montella M, Maso LD, Crovatto M, Parpinel M, Izzo F, Tommasi LG, Serraino D, La Vecchia C, Franceschi S (2007) Nutrients intake and the risk of hepatocellular carcinoma in Italy. Eur J Cancer 43(16):2381–2387. doi:10.1016/j.ejca.2007.07.012

    Article  CAS  PubMed  Google Scholar 

  37. Talamini R, Polesel J, Montella M, Dal Maso L, Crispo A, Tommasi LG, Izzo F, Crovatto M, La Vecchia C, Franceschi S (2006) Food groups and risk of hepatocellular carcinoma: a multicenter case–control study in Italy. Int J Cancer 119(12):2916–2921. doi:10.1002/ijc.22267

    Article  CAS  PubMed  Google Scholar 

  38. Yu SZ, Huang XE, Koide T, Cheng G, Chen GC, Harada K, Ueno Y, Sueoka E, Oda H, Tashiro F, Mizokami M, Ohno T, Xiang J, Tokudome S (2002) Hepatitis B and C viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in Haimen, China. Jpn J Cancer Res 93(12):1287–1292

    Article  CAS  PubMed  Google Scholar 

  39. Metwally NS, Kholeif TE, Ghanem KZ, Farrag AR, Ammar NM, Abdel-Hamid AH (2011) The protective effects of fish oil and artichoke on hepatocellular carcinoma in rats. Eur Rev Med Pharmacol Sci 15(12):1429–1444

    CAS  PubMed  Google Scholar 

  40. Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79(6):935–945

    CAS  PubMed  Google Scholar 

  41. Sanzo JM, Dorronsoro M, Amiano P, Amurrio A, Aguinagalde FX, Azpiri MA (2001) Estimation and validation of mercury intake associated with fish consumption in an EPIC cohort of Spain. Public Health Nutr 4(5):981–988

    Article  CAS  PubMed  Google Scholar 

  42. Sjodin A, Hagmar L, Klasson-Wehler E, Bjork J, Bergman A (2000) Influence of the consumption of fatty baltic sea fish on plasma levels of halogenated environmental contaminants in Latvian and Swedish men. Environ Health Perspect 108(11):1035–1041

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Rojas E, Herrera LA, Poirier LA, Ostrosky-Wegman P (1999) Are metals dietary carcinogens? Mutat Res 443(1–2):157–181

    Article  CAS  PubMed  Google Scholar 

  44. Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, Gerber L, Taylor LA, McKeever MG, Freedland SJ (2011) A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. Nutr Res 31(1):1–8. doi:10.1016/j.nutres.2011.01.002

    Article  CAS  PubMed  Google Scholar 

  45. Funahashi H, Satake M, Hasan S, Sawai H, Newman RA, Reber HA, Hines OJ, Eibl G (2008) Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth. Pancreas 36(4):353–362. doi:10.1097/MPA.0b013e31815ccc44

    Article  CAS  PubMed  Google Scholar 

  46. Tokudome S, Kuriki K, Suzuki S, Nahomi I, Goto C, Tokudome Y, Takeda E, Ichikawa Y, Okuyama H (2003) n-6 Polyunsaturated fatty acids and breast cancer. Nutr Cancer 47(2):210–212. doi:10.1207/s15327914nc4702_14

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors’ responsibilities were as follows—LS and LN: contributed to the study design and writing of the manuscript; GM and SK: contributed to the data search and data collection; GMJ, GH, and LK: contributed to the data extraction and quality assessment; and YCC: contributed to the data analysis.

Conflict of interest

This work was supported by a grant from the International S&T Cooperation Program of China (No. 2013DFA11150) and the Plan Project of Science & Technology from Jining city (2014JNNK21&2014JNYYF03). The authors have declared that no competing interests exist.

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Jining NO. 1 People’s Hospital, 6 Jiankang Road, Jining, 272011, China

    Min Gao

  2. Department of Hepatobiliary Surgery, Shandong Qianfoshan Hospital, 16766 Jingshi Road, Jinan, 250014, China

    Kai Sun

  3. Department of Radiology, Affiliated Hospital of Jining Medical University, 79 Guhuai Road, Jining, 272029, China

    Mujie Guo

  4. Department of Radiology, Jining NO. 2 People’s Hospital, 107 Hongxingdong Road, Jining, 272049, China

    Hang Gao

  5. Clinic Institute of Jining Medical University, 16 Hehua Road, Jining, 272067, China

    Kun Liu

  6. Department of Life Science, University of Jinan, 336 Nanxinzhuangxi Road, Jinan, 250022, China

    Cuicui Yang

  7. Department of Biochemistry, Dalian Medical University, Dalian, 116044, China

    Sheng Li

  8. Yulong Biomedical Group, Shanghai, 200433, China

    Sheng Li

  9. Department of Information Technology, Jining Medical University, 16 Hehua Road, Jining, 272067, China

    Ning Liu

Authors
  1. Min Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kai Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mujie Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cuicui Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ning Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ning Liu.

Additional information

Min Gao and Kai Sun have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, M., Sun, K., Guo, M. et al. Fish consumption and n-3 polyunsaturated fatty acids, and risk of hepatocellular carcinoma: systematic review and meta-analysis. Cancer Causes Control 26, 367–376 (2015). https://doi.org/10.1007/s10552-014-0512-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-014-0512-1

Keywords

Search

Navigation