Abstract
Purpose
Zinc is an essential micronutrient involving in multiple enzymatic reactions of human metabolism and biological functions affecting the cancer development. However, the relationship between dietary zinc intake and colorectal cancer (CRC) risk has been unclear. Herein, our study investigated the relationship between dietary zinc intake and CRC risk, and examined how the SLC30A8 rs3802177 genetic variant affects this association.
Methods
A total of 1431 CRC cases and 2704 controls were selected to investigate the relationship between dietary zinc intake and CRC risk. After excluding individuals without genotype data, 1097 CRC cases and 1559 controls were used to evaluate the interaction between dietary zinc intake and the rs3802177 polymorphism in CRC risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were measured using unconditional logistic regression models.
Results
Higher dietary zinc intake was inversely associated with the risk of CRC in the total population [adjusted OR (aOR) = 0.80, 95% CI 0.66–0.96, p for trend = 0.018]. In the codominant model, G+ carriers of the SLC30A8 rs3802177 with higher consumption of zinc were observed to have a significantly lower risk of CRC in all participants (p for interaction = 0.020). In females, GG carriers with higher zinc intake showed a stronger protective effect against the development of CRC (p for interaction = 0.008).
Conclusions
In summary, our findings suggest an inverse association between dietary zinc intake and CRC risk, and this relationship may be modified by SLC30A8 rs3802177 polymorphism.
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Ahn Y, Kwon E, Shim JE, Park MK, Joo Y, Kim K et al (2008) Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr 61:1435–1441. https://doi.org/10.1038/sj.ejcn.1602657
Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V et al (2012) Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res 2012:7891. https://doi.org/10.1155/2012/789174
Barch DH, Kuemmerle SC, Hollenberg PF, Iannaccone PM (1984) Esophageal microsomal metabolism of N-nitrosomethylbenzylamine in the zinc-deficient rat. Can Res 44(12 Pt 1):5629–5633
Bin BH, Seo J, Kim ST (2018) Function, structure, and transport aspects of ZIP and ZnT Zinc transporters in immune cells. J Immunol Res 2018:9365747. https://doi.org/10.1155/2018/9365747
Chadha VD, Vaiphei K, Dhawan DK (2007) Zinc mediated normalization of histoarchitecture and antioxidant status offers protection against initiation of experimental carcinogenesis. Mol Cell Biochem 304(1):101–108. https://doi.org/10.1007/s11010-007-9490-x
Chimienti F, Sv D, Fo P, Schuit F, Garcia-Cuenca R, Vandewalle B et al (2006) In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion. J Cell Sci 119(20):4199–4206. https://doi.org/10.1242/jcs.03164
Clinton SK, Giovannucci EL, Hursting SD (2020) The world cancer research fund/American institute for cancer research third expert report on diet, nutrition, physical activity, and cancer: impact and future directions. J Nutr 150(4):663–671. https://doi.org/10.1093/jn/nxz268
Corella D, Coltell O, Sorlí JV, Estruch R, Quiles L, Martínez-González MÁ et al (2016) Polymorphism of the transcription factor 7-like 2 gene (TCF7L2) interacts with obesity on type-2 diabetes in the predimed study emphasizing the heterogeneity of genetic variants in type-2 diabetes risk prediction: time for obesity-specific genetic risk scores. Nutrients 8(12):793. https://doi.org/10.3390/nu8120793
Dani V, Goel A, Vaiphei K, Dhawan DK (2007) Chemopreventive potential of zinc in experimentally induced colon carcinogenesis. Toxicol Lett 171(1):10–18. https://doi.org/10.1016/j.toxlet.2007.02.002
Deng L, Gui Z, Zhao L, Wang J, Shen L (2012) Diabetes mellitus and the incidence of colorectal cancer: an updated systematic review and meta-analysis. Dig Dis Sci 57(6):1576–1585. https://doi.org/10.1007/s10620-012-2055-1
Dimou N, Kim AE, Flanagan O, Murphy N, Diez-Obrero V, Shcherbina A et al (2023) Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses. Br J Cancer 129(3):511–520. https://doi.org/10.1038/s41416-023-02312-z
Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131(11):S3109–S3120. https://doi.org/10.1093/jn/131.11.3109S
Gu H (2015) Genetic, epigenetic and biological effects of zinc transporter (SLC30A8) in type 1 and type 2 diabetes. Curr Diabetes Rev. https://doi.org/10.2174/1573399812666151123104540
Gunathilake M, Lee J, Ae Cho Y, Hwan OJ, Jin Chang H, Kyung Sohn D et al (2018) Interaction between physical activity, PITX1 rs647161 genetic polymorphism and colorectal cancer risk in a Korean population: a case-control study. Oncotarget. https://doi.org/10.18632/oncotarget.24136
Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N et al (2012) Zinc and heme iron intakes and risk of colorectal cancer: a population-based prospective cohort study in Japan. Am J Clin Nutr 96:864–873. https://doi.org/10.3945/ajcn.112.041202
He XY, Xiang C, Zhang CX, Xie YY, Chen L, Zhang GX et al (2015) p53 in the myeloid lineage modulates an inflammatory microenvironment limiting initiation and invasion of intestinal tumors. Cell Rep 13(5):888–897. https://doi.org/10.1016/j.celrep.2015.09.045
Ho E (2004) Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem 15(10):572–578. https://doi.org/10.1016/j.jnutbio.2004.07.005
Ho E, Ames BN (2002) Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFκB, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line. Proc Natl Acad Sci 99(26):16770–16775. https://doi.org/10.1073/pnas.222679399
Hoang BX, Han B, Shaw DG, Nimni M (2016) Zinc as a possible preventive and therapeutic agent in pancreatic, prostate, and breast cancer. Eur J Cancer Prev 25(5):457–461. https://doi.org/10.1097/CEJ.0000000000000194
Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, Yamagata K et al (2008) Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab 93(8):3136–3141. https://doi.org/10.1210/jc.2008-0452
Huang X, Liu G, Guo J, Su Z (2018) The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci 14(11):1483–1496. https://doi.org/10.7150/ijbs.27173
Jaiswal AS, Narayan S (2004) Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cells. J Cell Biochem 93(2):345–357. https://doi.org/10.1002/jcb.20156
Johnson CH, Golla JP, Dioletis E, Singh S, Ishii M, Charkoftaki G et al (2021) Molecular mechanisms of alcohol-induced colorectal carcinogenesis. Cancers. https://doi.org/10.3390/cancers13174404
Jung SY, Mancuso N, Han S, Zhang Z-F (2020) The role of genetically determined glycemic traits in breast cancer: a mendelian randomization study. Front Genet. https://doi.org/10.3389/fgene.2020.540724
Kang YJ, Zhou Z (2005) Zinc prevention and treatment of alcoholic liver disease. Mol Aspects Med 26(4):391–404. https://doi.org/10.1016/j.mam.2005.07.002
Kang MJ, Won YJ, Lee JJ, Jung KW, Kim HJ, Kong HJ et al (2022) Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2019. Cancer Res Treat 54(2):330–344. https://doi.org/10.4143/crt.2022.128
Khoshdel Z, Naghibalhossaini F, Abdollahi K, Shojaei S, Moradi M, Malekzadeh M (2016) Serum copper and zinc levels among Iranian colorectal cancer patients. Biol Trace Elem Res 170(2):294–299. https://doi.org/10.1007/s12011-015-0483-4
Koveitypour Z, Panahi F, Vakilian M, Peymani M, Seyed Forootan F, Nasr Esfahani MH et al (2019) Signaling pathways involved in colorectal cancer progression. Cell Biosci 9:97–97. https://doi.org/10.1186/s13578-019-0361-4
Lee DH, Anderson KE, Harnack LJ, Folsom AR, Jacobs DR Jr (2004) Heme iron, zinc, alcohol consumption, and colon cancer: Iowa women’s health study. JNCI J Natl Cancer Inst. 96(5):403–407. https://doi.org/10.1093/jnci/djh047
Li P, Xu J, Shi Y, Ye Y, Chen K, Yang J et al (2014) Association between zinc intake and risk of digestive tract cancers: a systematic review and meta-analysis. Clin Nutr 33(3):415–420. https://doi.org/10.1016/j.clnu.2013.10.001
Lin Y, Li P, Cai L, Zhang B, Tang X, Zhang X et al (2010) Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population. BMC Med Genet 11(1):97. https://doi.org/10.1186/1471-2350-11-97
Lu Y, Kweon SS, Cai Q, Tanikawa C, Shu X, Jia WH et al (2019) Identification of novel loci and new risk variant in known loci for colorectal cancer risk in East Asians. Cancer Epidemiol Biomarkers Prev. https://doi.org/10.1158/1055-9965.EPI-19-0755
Luo H, Fang YJ, Zhang X, Feng XL, Zhang NQ, Abulimiti A et al (2021) Association between dietary zinc and selenium intake, oxidative stress-related gene polymorphism, and colorectal cancer risk in chinese population - a case-control study. Nutr Cancer 73(9):1621–1630. https://doi.org/10.1080/01635581.2020.1804950
Molina-Montes E, Coscia C, Gómez-Rubio P, Fernández A, Boenink R, Rava M et al (2021) Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses. Gut 70(2):319. https://doi.org/10.1136/gutjnl-2019-319990
Oneta CM, Lieber CS, Li J, Rüttimann S, Schmid B, Lattmann J et al (2002) Dynamics of cytochrome P4502E1 activity in man: induction by ethanol and disappearance during withdrawal phase. J Hepatol 36(1):47–52. https://doi.org/10.1016/s0168-8278(01)00223-9
Qiao L, Feng Y (2013) Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies. Cancer Causes Control 24(6):1175–1183. https://doi.org/10.1007/s10552-013-0197-x
Sainz J, Rudolph A, Hoffmeister M, Frank B, Brenner H, Chang-Claude J et al (2012) Effect of type 2 diabetes predisposing genetic variants on colorectal cancer risk. J Clin Endocrinol Metab 97(5):E845–E851. https://doi.org/10.1210/jc.2011-2565
Seitz HK, Maurer B, Stickel F (2006) Alcohol consumption and cancer of the gastrointestinal tract. Dig Dis 23(3–4):297–303. https://doi.org/10.1159/000090177
Solomou A, Philippe E, Chabosseau P, Migrenne-Li S, Gaitan J, Lang J et al (2016) Over-expression of Slc30a8/ZnT8 selectively in the mouse α cell impairs glucagon release and responses to hypoglycemia. Nutr Metab 13(1):46. https://doi.org/10.1186/s12986-016-0104-z
Song M, Garrett WS, Chan AT (2015) Nutrients, foods, and colorectal cancer prevention. Gastroenterology 148(6):1244-1260.e1216. https://doi.org/10.1053/j.gastro.2014.12.035
Stepien M, Jenab M, Freisling H, Becker NP, Czuban M, Tjonneland A et al (2017) Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European prospective investigation into cancer and nutrition cohort. Carcinogenesis 38(7):699–707. https://doi.org/10.1093/carcin/bgx051
Sun L, Yu S (2012) Diabetes mellitus is an independent risk factor for colorectal cancer. Dig Dis Sci 57(6):1586–1597. https://doi.org/10.1007/s10620-012-2059-x
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660
Tang XH, Shay NF (2001) Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes. J Nutr 131(5):1414–1420. https://doi.org/10.1093/jn/131.5.1414
van Lee L, Heyworth J, McNaughton S, Iacopetta B, Clayforth C, Fritschi L (2011) Selected dietary micronutrients and the risk of right- and left-sided colorectal cancers: a case-control study in Western Australia. Ann Epidemiol 21(3):170–177. https://doi.org/10.1016/j.annepidem.2010.10.005
Virgili F, Ambra R, McCormack J, Simpson EAE, Ciarapica D, Barnaba L et al (2018) Genetic polymorphisms and zinc status: implications for supplementation in metabolic diseases. Curr Pharm Des 24(35):4131–4143. https://doi.org/10.2174/1381612824666181016155903
Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65(4 Suppl):1220S-1228S. https://doi.org/10.1093/ajcn/65.4.1220S
Wong MC, Ding H, Wang J, Chan PS, Huang J (2019) Prevalence and risk factors of colorectal cancer in Asia. Intest Res 17(3):317–329. https://doi.org/10.5217/ir.2019.00021
Yan M, Song Y, Wong CP, Hardin K, Ho E (2008) Zinc deficiency alters DNA damage response genes in normal human prostate epithelial cells. J Nutr 138(4):667–673. https://doi.org/10.1093/jn/138.4.667
Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X (2019) Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer 18(1):26. https://doi.org/10.1186/s12943-019-0954-x
Yu GH, Li SF, Wei R, Jiang Z (2022) Diabetes and colorectal cancer risk: clinical and therapeutic implications. J Diabetes Res 2022:1747326. https://doi.org/10.1155/2022/1747326
Zhang X, Giovannucci EL, Smith-Warner SA, Wu K, Fuchs CS, Pollak M et al (2011) A prospective study of intakes of zinc and heme iron and colorectal cancer risk in men and women. Cancer Causes Control 22(12):1627–1637. https://doi.org/10.1007/s10552-011-9839-z
Zhang C, Cheng R, Ding J, Li X, Niu H, Li X (2022) Serum copper and zinc levels and colorectal cancer in adults: findings from the national health and nutrition examination 2011–2016. Biol Trace Elem Res 200(5):2033–2039. https://doi.org/10.1007/s12011-021-02826-8
Funding
This work was supported by the International Cooperation and Education Program (NCCRI•NCCI 52210–52211, 2022) of the National Cancer Center, Korea, and grants from the National Cancer Center, Korea (2310470), and National Research Foundation of Korea (2021R1A2C2008439).
Author information
Authors and Affiliations
Contributions
LTDN designed and conducted the research, analyzed the data, and wrote the manuscript draft. MG analyzed the data and revised the manuscript draft. JL collected the data. JHO collected the data. HJC collected the data. DKS collected the data. AS designed and conducted the research. JSK designed and conducted the research and revised the manuscript draft. All authors read and approved the final paper.
Corresponding author
Ethics declarations
Conflict of interests
The authors have no relevant financial or non-financial interests to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Nguyen, L.T.D., Gunathilake, M., Lee, J. et al. Zinc intake, SLC30A8 rs3802177 polymorphism, and colorectal cancer risk in a Korean population: a case–control study. J Cancer Res Clin Oncol 149, 16429–16440 (2023). https://doi.org/10.1007/s00432-023-05381-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-023-05381-y