Associations among dietary seaweed intake, c-MYC rs6983267 polymorphism, and risk of colorectal cancer in a Korean population: a case–control study

  • Jimi Kim
  • Jeonghee Lee
  • Jae Hwan Oh
  • Hee Jin Chang
  • Dae Kyung Sohn
  • Aesun Shin
  • Jeongseon KimEmail author
Original Contribution



The effects of seaweed compounds have been studied in relation to colorectal cancer (CRC) based on their ability to modulate carcinogen metabolism in vivo and in vitro. However, no epidemiological studies on the interaction between edible seaweed and genetic variants relevant to CRC have been reported. This study examined the associations among dietary seaweed intake (gim, miyeok, and dashima), single-nucleotide polymorphisms (SNPs; rs6983267, rs7014346, and rs719725), and CRC risk in a Korean population.


The participants comprised 923 CRC patients and 1846 controls who visited the National Cancer Center Korea. We used a Semiquantitative Food Frequency Questionnaire and genotyped SNPs using genomic DNA samples.


The intake of total seaweed, miyeok, and dashima showed a significant inverse association with CRC risk after adjusting for potential confounding factors (total seaweed odds ratio (OR) [95% CI] = 0.65 [0.50–0.85], P for trend < 0.001; miyeok = 0.82 [0.62–1.09], P for trend < 0.05; dashima = 0.58 [0.44–0.76], P for trend < 0.001, highest vs. lowest tertile). We confirmed that the homozygous T/T allele of rs6983267 c-MYC indicated an interaction between dietary seaweed intake and both overall CRC and rectal cancer (CRC OR [95% CI] = 0.52 [0.34–0.81], P for interaction = 0.015; rectal cancer = 0.45 [0.25–0.79], P for interaction = 0.007, T/T carriers with high total seaweed intake vs. T/T carriers with low total seaweed intake).


This study provides evidence of the effect of dietary seaweed intake on CRC risk with respect to c-MYC gene variants.


Seaweed c-MYC rs6983267 Genetic polymorphism Colorectal cancer 



Body mass index


Confidence interval


Colorectal cancer


Genome-wide association study


Hardy–Weinberg equilibrium


Odds ratio


Single-nucleotide polymorphism


Semiquantitative Food Frequency Questionnaire



We are thankful to all participants involved in this study. This research was supported by grants from the National Cancer Center in Korea (1710882, 1810090).

Author contributions

The authors’ responsibilities were as follows: JMK and JSK designed the research, performed the statistical analysis, and had primary responsibility for the final content; JL, JHO, HJC, DKS, and AS recruited the study participants, collected the data, and conducted the research; JMK and JSK wrote the manuscript; and all authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors (Jimi Kim, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, and Jeongseon Kim) declare that they have no conflicts of interest.

Ethical standards

Written and signed informed consent was obtained from all patients in adherence to the National Cancer Center Korea guidelines. This study was approved by the Institutional Review Board of the National Cancer Center Korea (IRB no. NCCNCS-10-350 and no. NCC2015-0202).

Supplementary material

394_2019_2046_MOESM1_ESM.docx (33 kb)
Table S1. Description of SNPs (DOCX 34 kb)
394_2019_2046_MOESM2_ESM.pdf (110 kb)
Supplementary figure 1. Flow chart of case and control recruitment (PDF 110 kb)


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–386. CrossRefGoogle Scholar
  2. 2.
    Haggar FA, Boushey RP (2009) Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 22(4):191–197. CrossRefGoogle Scholar
  3. 3.
    Hughes LAE, Simons C, van den Brandt PA, van Engeland M, Weijenberg MP (2017) Lifestyle, diet, and colorectal cancer risk according to (Epi)genetic instability: current evidence and future directions of molecular pathological epidemiology. Curr Colorectal Cancer Rep 13(6):455–469. CrossRefGoogle Scholar
  4. 4.
    Park Y, Lee J, Oh JH, Shin A, Kim J (2016) Dietary patterns and colorectal cancer risk in a Korean population: a case–control study. Medicine (Baltimore) 95(25):e3759. CrossRefGoogle Scholar
  5. 5.
    Brown ES, Allsopp PJ, Magee PJ, Gill CI, Nitecki S, Strain CR, McSorley EM (2014) Seaweed and human health. Nutr Rev 72(3):205–216. CrossRefGoogle Scholar
  6. 6.
    Susan Løvstad Holdt SK (2011) Bioactive compounds in seaweed: functional food applications and legislation. J Appl Phycol 23(3):543–597CrossRefGoogle Scholar
  7. 7.
    Rupérez P (2002) Mineral content of edible marine seaweeds. Food Chem 79(1):23–26. CrossRefGoogle Scholar
  8. 8.
    Gutierrez-Rodriguez AG, Juarez-Portilla C, Olivares-Banuelos T, Zepeda RC (2018) Anticancer activity of seaweeds. Drug Discov Today 23(2):434–447. CrossRefGoogle Scholar
  9. 9.
    Ruan BF, Ge WW, Lin MX, Li QS (2018) A review of the components of seaweeds as potential candidates in cancer therapy. Anticancer Agents Med Chem 18(3):354–366. CrossRefGoogle Scholar
  10. 10.
    Tenesa A, Dunlop MG (2009) New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 10(6):353–358. CrossRefGoogle Scholar
  11. 11.
    Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W et al (2007) A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet 39(8):984–988. CrossRefGoogle Scholar
  12. 12.
    Tenesa A, Farrington SM, Prendergast JG, Porteous ME, Walker M, Haq N, Barnetson RA, Theodoratou E, Cetnarskyj R, Cartwright N et al (2008) Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet 40(5):631–637. CrossRefGoogle Scholar
  13. 13.
    Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, Farrington SM, Prendergast J, Olschwang S, Chiang T, Crowdy E et al (2007) Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet 39(8):989–994. CrossRefGoogle Scholar
  14. 14.
    Poynter JN, Figueiredo JC, Conti DV, Kennedy K, Gallinger S, Siegmund KD, Casey G, Thibodeau SN, Jenkins MA, Hopper JL et al (2007) Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry. Cancer Res 67(23):11128–11132. CrossRefGoogle Scholar
  15. 15.
    Nan H, Morikawa T, Suuriniemi M, Imamura Y, Werner L, Kuchiba A, Yamauchi M, Hunter DJ, Kraft P, Giovannucci EL et al (2013) Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer according to CTNNB1 alterations. J Natl Cancer Inst 105(24):1852–1861. CrossRefGoogle Scholar
  16. 16.
    Xiong F, Wu C, Bi X, Yu D, Huang L, Xu J, Zhang T, Zhai K, Chang J, Tan W et al (2010) Risk of genome-wide association study-identified genetic variants for colorectal cancer in a Chinese population. Cancer Epidemiol Biomark Prev 19(7):1855–1861. CrossRefGoogle Scholar
  17. 17.
    Murphy DJ, Junttila MR, Pouyet L, Karnezis A, Shchors K, Bui DA, Brown-Swigart L, Johnson L, Evan GI (2008) Distinct thresholds govern Myc's biological output in vivo. Cancer Cell 14(6):447–457. CrossRefGoogle Scholar
  18. 18.
    Moussavou G, Kwak DH, Obiang-Obonou BW, Maranguy CA, Dinzouna-Boutamba SD, Lee DH, Pissibanganga OG, Ko K, Seo JI, Choo YK (2014) Anticancer effects of different seaweeds on human colon and breast cancers. Mar Drugs 12(9):4898–4911. CrossRefGoogle Scholar
  19. 19.
    Zorofchian Moghadamtousi S, Karimian H, Khanabdali R, Razavi M, Firoozinia M, Zandi K, Abdul Kadir H (2014) Anticancer and antitumor potential of fucoidan and fucoxanthin, two main metabolites isolated from brown algae. Sci World J 2014:768323. CrossRefGoogle Scholar
  20. 20.
    Kim EJ, Park SY, Lee JY, Park JH (2010) Fucoidan present in brown algae induces apoptosis of human colon cancer cells. BMC Gastroenterol 10:96. CrossRefGoogle Scholar
  21. 21.
    Park HK, Kim IH, Kim J, Nam TJ (2012) Induction of apoptosis by laminarin, regulating the insulin-like growth factor-IR signaling pathways in HT-29 human colon cells. Int J Mol Med 30(4):734–738. CrossRefGoogle Scholar
  22. 22.
    Park HK, Kim IH, Kim J, Nam TJ (2013) Induction of apoptosis and the regulation of ErbB signaling by laminarin in HT-29 human colon cancer cells. Int J Mol Med 32(2):291–295. CrossRefGoogle Scholar
  23. 23.
    Kazlowska K, Lin HT, Chang SH, Tsai GJ (2013) In Vitro and In Vivo anticancer effects of sterol fraction from red algae Porphyra dentata. Evid Based Complement Altern Med 2013:493869. CrossRefGoogle Scholar
  24. 24.
    Ahn Y, Kwon E, Shim JE, Park MK, Joo Y, Kimm K, Park C, Kim DH (2007) Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr 61(12):1435–1441. CrossRefGoogle Scholar
  25. 25.
    Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65(4 Suppl):1220S–1228S (discussion 1229S–1231S) CrossRefGoogle Scholar
  26. 26.
    Hoshiyama Y, Sasaba T (1992) A case–control study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan. Cancer Causes Control 3(5):441–448CrossRefGoogle Scholar
  27. 27.
    Yang YJ, Nam SJ, Kong G, Kim MK (2010) A case–control study on seaweed consumption and the risk of breast cancer. Br J Nutr 103(9):1345–1353. CrossRefGoogle Scholar
  28. 28.
    Michikawa T, Inoue M, Shimazu T, Sawada N, Iwasaki M, Sasazuki S, Yamaji T, Tsugane S, Japan Public Health Center-based Prospective Study G (2012) Seaweed consumption and the risk of thyroid cancer in women: the Japan Public Health Center-based Prospective Study. Eur J Cancer Prev 21(3):254–260. CrossRefGoogle Scholar
  29. 29.
    Hoshiyama Y, Sekine T, Sasaba T (1993) A case–control study of colorectal cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan. Tohoku J Exp Med 171(2):153–165CrossRefGoogle Scholar
  30. 30.
    MacArtain P, Gill CI, Brooks M, Campbell R, Rowland IR (2007) Nutritional value of edible seaweeds. Nutr Rev 65(12 Pt 1):535–543CrossRefGoogle Scholar
  31. 31.
    Ruan BF, Ge WW, Lin MX, Li QS (2017) A review of the components of seaweeds as potential candidates in cancer therapy. Anticancer Agents Med Chem. Google Scholar
  32. 32.
    Evan GI, Vousden KH (2001) Proliferation, cell cycle and apoptosis in cancer. Nature 411(6835):342–348. CrossRefGoogle Scholar
  33. 33.
    Hosokawa M, Kudo M, Maeda H, Kohno H, Tanaka T, Miyashita K (2004) Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPAR gamma ligand, troglitazone, on colon cancer cells. Biochim Biophys Acta 1675(1–3):113–119. CrossRefGoogle Scholar
  34. 34.
    Kim JM, Araki S, Kim DJ, Park CB, Takasuka N, Baba-Toriyama H, Ota T, Nir Z, Khachik F, Shimidzu N et al (1998) Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation. Carcinogenesis 19(1):81–85CrossRefGoogle Scholar
  35. 35.
    Das SK, Hashimoto T, Shimizu K, Yoshida T, Sakai T, Sowa Y, Komoto A, Kanazawa K (2005) Fucoxanthin induces cell cycle arrest at G0/G1 phase in human colon carcinoma cells through up-regulation of p21WAF1/Cip1. Biochim Biophys Acta 1726(3):328–335. CrossRefGoogle Scholar
  36. 36.
    Hyun JH, Kim SC, Kang JI, Kim MK, Boo HJ, Kwon JM, Koh YS, Hyun JW, Park DB, Yoo ES et al (2009) Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells. Biol Pharm Bull 32(10):1760–1764CrossRefGoogle Scholar
  37. 37.
    Go H, Hwang HJ, Nam TJ (2010) A glycoprotein from Laminaria japonica induces apoptosis in HT-29 colon cancer cells. Toxicol In Vitro 24(6):1546–1553. CrossRefGoogle Scholar
  38. 38.
    Jeong SY, Seol DW (2008) The role of mitochondria in apoptosis. BMB Rep 41(1):11–22CrossRefGoogle Scholar
  39. 39.
    Mellier G, Huang S, Shenoy K, Pervaiz S (2010) TRAILing death in cancer. Mol Asp Med 31(1):93–112. CrossRefGoogle Scholar
  40. 40.
    Hutter CM, Slattery ML, Duggan DJ, Muehling J, Curtin K, Hsu L, Beresford SA, Rajkovic A, Sarto GE, Marshall JR et al (2010) Characterization of the association between 8q24 and colon cancer: gene-environment exploration and meta-analysis. BMC Cancer 10:670. CrossRefGoogle Scholar
  41. 41.
    Li L, Lv L, Liang Y, Shen X, Zhou S, Zhu J, Ma R (2015) Association of 8q23-24 region (8q23.3 loci and 8q24.21 loci) with susceptibility to colorectal cancer: a systematic and updated meta-analysis. Int J Clin Exp Med 8(11):21001–21013Google Scholar
  42. 42.
    Tuupanen S, Niittymaki I, Nousiainen K, Vanharanta S, Mecklin JP, Nuorva K, Jarvinen H, Hautaniemi S, Karhu A, Aaltonen LA (2008) Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution. Cancer Res 68(1):14–17. CrossRefGoogle Scholar
  43. 43.
    Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, Bjorklund M, Wei G, Yan J, Niittymaki I et al (2009) The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet 41(8):885–890. CrossRefGoogle Scholar
  44. 44.
    Bienz M, Clevers H (2000) Linking colorectal cancer to Wnt signaling. Cell 103(2):311–320CrossRefGoogle Scholar
  45. 45.
    Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19(1):1–11CrossRefGoogle Scholar
  46. 46.
    Sur IK, Hallikas O, Vaharautio A, Yan J, Turunen M, Enge M, Taipale M, Karhu A, Aaltonen LA, Taipale J (2012) Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors. Science 338(6112):1360–1363. CrossRefGoogle Scholar
  47. 47.
    Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M et al (2009) The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet 41(8):882–884. CrossRefGoogle Scholar
  48. 48.
    Sugimachi K, Niida A, Yamamoto K, Shimamura T, Imoto S, Iinuma H, Shinden Y, Eguchi H, Sudo T, Watanabe M et al (2014) Allelic imbalance at an 8q24 oncogenic SNP is involved in activating MYC in human colorectal cancer. Ann Surg Oncol 21(Suppl 4):S515–521. CrossRefGoogle Scholar
  49. 49.
    Xue M, Ge Y, Zhang J, Liu Y, Wang Q, Hou L, Zheng Z (2013) Fucoidan inhibited 4T1 mouse breast cancer cell growth in vivo and in vitro via downregulation of Wnt/beta-catenin signaling. Nutr Cancer 65(3):460–468. CrossRefGoogle Scholar
  50. 50.
    Tamas K, Walenkamp AM, de Vries EG, van Vugt MA, Beets-Tan RG, van Etten B, de Groot DJ, Hospers GA (2015) Rectal and colon cancer: not just a different anatomic site. Cancer Treat Rev 41(8):671–679. CrossRefGoogle Scholar
  51. 51.
    Li FY, Lai MD (2009) Colorectal cancer, one entity or three. J Zhejiang Univ Sci B 10(3):219–229. CrossRefGoogle Scholar
  52. 52.
    Muzny DMBM, Chang K, Dinh HH, Drummond JA, Fowler G, Kovar CL, Lewis LR, Morgan MB, Newsham IF et al (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337. CrossRefGoogle Scholar
  53. 53.
    Kapiteijn E, Liefers GJ, Los LC, Kranenbarg EK, Hermans J, Tollenaar RA, Moriya Y, van de Velde CJ, van Krieken JH (2001) Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol 195(2):171–178. CrossRefGoogle Scholar
  54. 54.
    Kato I, Tominaga S, Matsuura A, Yoshii Y, Shirai M, Kobayashi S (1990) A comparative case–control study of colorectal cancer and adenoma. Jpn J Cancer Res 81(11):1101–1108CrossRefGoogle Scholar
  55. 55.
    Hong SN, Park C, Kim JI, Kim DH, Kim HC, Chang DK, Rhee PL, Kim JJ, Rhee JC, Son HJ et al (2015) Colorectal cancer-susceptibility single-nucleotide polymorphisms in Korean population. J Gastroenterol Hepatol 30(5):849–857. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Cancer Biomedical Science, Graduate School of Cancer Science and PolicyNational Cancer CenterGoyang-siSouth Korea
  2. 2.Center for Colorectal Cancer, National Cancer Center HospitalNational Cancer CenterGoyang-siSouth Korea
  3. 3.Department of Preventive MedicineSeoul National University College of MedicineSeoulSouth Korea

Personalised recommendations