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Obesity-related genes variability in Czech patients with sporadic colorectal cancer: preliminary results

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Abstract

Background

Genetic variability in obesity-related genes and the resulting phenotypes are being recognized as major risk factors for colorectal cancer and/or severity of the disease.

Materials and methods

A total of 102 patients (aged 68 ± 10.2 years, 79 men and 23 women) and 101 age-matched (68.1 ± 5.4 years old) individuals without colorectal cancer, 59 men and 42 women, were recruited. All the individuals were genotyped for the following subset of polymorphisms in obesity-related genes: angiotensinogen gene (M235T and -6A/G), in IL-6 gene (-174 G/C and -596 A/G), in leptin gene (-2548 A/G), and polymorphism Gln223Arg within the leptin receptor (LEPR) gene.

Results

A significant increase in frequency of double heterozygote genotype (MTAG) of both angiotensinogen polymorphisms in males with colorectal cancer was observed when compared to control men [odds ratio (OR) = 3.77, P corr = 0.001]. A marginally significant difference in genotype distribution of -174 G/C IL-6 polymorphism between the patients in stage I–II compared to patients in III–IV was found (P g = 0.05, P a = 0.173). The GG genotype of -174 G/C IL-6 polymorphism in the patients in stage III–IV carries an increased risk compared to those in stage I–II (OR = 2.83, P corr = 0.06). Similarly, a difference in genotype distribution of Gln223Arg in LEPR gene between the patients staged I–II compared to III–IV was observed (P g = 0.05). The AA genotype was shown to be risky for the patients staged III–IV (OR = 3.35, P corr = 0.06).

Conclusions

The investigated single nucleotide polymorphisms within the genes encoding for obesity-related genes were observed to be associated both with clinical manifestation of colorectal cancer and with severity of the disease. Thus, we suggest that defined genetic variability in the genes might become DNA markers for colorectal cancer in the future.

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References

  1. Bray GA, Paeratakul S, Popkin BM (2004) Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol Behav 83:549–555

    Article  PubMed  CAS  Google Scholar 

  2. John BJ, Irukulla S, Abulafi AM, Kumar D, Mendall MA (2006) Systematic review: adipose tissue, obesity and gastrointestinal diseases. Aliment Pharmacol Ther 23:1511–1523

    Article  PubMed  CAS  Google Scholar 

  3. Rondinone CM (2006) Adipocyte-derived hormones, cytokines, and mediators. Endocrine 29:81–90

    Article  PubMed  CAS  Google Scholar 

  4. Sherman CT, Brasier AR (2001) Role of signal transducers and activators of transcription 1 and -3 in inducible regulation of the human angiotensinogen gene by interleukin-6. Mol Endocrinol 15:441–457

    Article  PubMed  Google Scholar 

  5. Ronti T, Lupattelli G, Mannarino E (2006) The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf) 64:355–365

    CAS  Google Scholar 

  6. Mohamed-Ali V, Pinkney JH, Coppack SW (1998) Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord 22:1145–1158

    Article  PubMed  CAS  Google Scholar 

  7. Makino T, Noguchi Y, Yoshikawa T, Doi C, Nomura K (1998) Circulating interleukin 6 concentrations and insulin resistance in patients with cancer. Br J Surg 85:1658–1662

    Article  PubMed  CAS  Google Scholar 

  8. Dymicka-Piekarska V, Matowicka-Karna J, Gryko M, Kemona-Chetnik I, Kemona H (2007) Relationship between soluble P-selectin and inflammatory factors (interleukin-6 and C-reactive protein) in colorectal cancer. Thromb Res 120:585–590

    Article  PubMed  CAS  Google Scholar 

  9. Chung YC, Chaen YL, Hsu CP (2006) Clinical significance of tissue expression of interleukin-6 in colorectal carcinoma. Anticancer Res 26:3905–3911

    PubMed  CAS  Google Scholar 

  10. Ahima RS, Osei SY (2001) Molecular regulation of eating behavior: new insights and prospects for therapeutic strategies. Trends Mol Med 7:205–213

    Article  PubMed  CAS  Google Scholar 

  11. Zhang F, Chen Y, Heiman M, Dimarchi R (2005) Leptin: structure, function and biology. Vitam Horm 71:345–372

    Article  PubMed  CAS  Google Scholar 

  12. Papathanassoglou E, El-Haschimi K, Li XC, Matarese G, Strom T, Mantzoros C (2006) Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. J Immunol 176:7745–7752

    PubMed  CAS  Google Scholar 

  13. Moses AG, Dowidar N, Holloway B, Waddell I, Fearon KC, Ross JA (2001) Leptin and its relation to weight loss, ob gene expression and the acute-phase response in surgical patients. Br J Surg 88:588–593

    Article  PubMed  CAS  Google Scholar 

  14. Attoub S, Noe V, Pirola L, Bruyneel E, Chastre E, Mareel M et al (2000) Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways. FASEB J 14:2329–2338

    Article  PubMed  CAS  Google Scholar 

  15. Russ AP, Maerz W, Ruzicka V, Stein U, Gross W (1993) Rapid detection of the hypertension-associated Met235®Thr allele of the human angiotensinogen gene. Hum Mol Genet 5:609–610

    Article  Google Scholar 

  16. Hegele RA, Harris SB, Hanley AJ, Sun F, Connelly PW, Zinman B (1998) -6A promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree. J Hum Genet 43:37–41

    Article  PubMed  CAS  Google Scholar 

  17. Vasku JA, Vasku A, Goldbergova M, Vasku V (2004) Heterozygote AG variant of -596 A/G IL-6 gene polymorphism is a marker for cutaneous T-cell lymphoma (CTCL). Clin Immunol 113:256–560

    Article  PubMed  CAS  Google Scholar 

  18. Mammés O, Betoulle D, Aubert R, Herbeth B, Siest G, Fumeron F (2000) Association of the G-2548A polymorphism in the 5¢ region of the LEP gene with overweight. Ann Hum Genet 64:391–394

    Article  PubMed  Google Scholar 

  19. Mammés O, Aubert R, Betoulle D, Pean F, Herbeth B, Visvikis S et al (2001) LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women. Eur J Clin Invest 5:398–404

    Article  Google Scholar 

  20. Murty VV, Li RG, Mathew S, Reuter VE, Bronson DL, Bosl GJ et al (1994) Replication error-type genetic instability at 1q42-43 in human male germ cell tumors. Cancer Res 54:3983–3985

    PubMed  CAS  Google Scholar 

  21. Theodoropoulos G, Papaconstantinou I, Felekouras E, Nikiteas N, Karakitsos P, Panoussopoulos D et al (2006) Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer. World J Gastroenterol 12:5037–5043

    PubMed  CAS  Google Scholar 

  22. Slattery ML, Wolff RK, Herrick JS, Caan BJ, Potter JD (2007) IL6 genotypes and colon and rectal cancer. Cancer Causes Control 18:1095–1105

    Article  PubMed  Google Scholar 

  23. Tan D, Wu X, Hou M, Lee SO, Lou W, Wang J, Janarthan B, Nallapareddy S, Trump DL, Gao AC (2005) Interleukin-6 polymorphism is associated with more aggressive prostate cancer. J Urol 174:753–756

    Article  PubMed  CAS  Google Scholar 

  24. Brozek W, Bises G, Fabjani G, Cross HS, Peterlik M (2008) Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells. BMC Cancer 18:13

    Article  Google Scholar 

  25. Hoffstedt J, Eriksson P, Mottagui-Tabar S, Arner P (2002) A polymorphism in the leptin gene promoter region (-2548 g/a) influences gene expression and adipose tissue secretion of leptin. Horm Metab Res 34:355–359

    Article  PubMed  CAS  Google Scholar 

  26. Slattery ML, Wolff RK, Herrick J, Caan BJ, Potter JD (2008) Leptin and leptin receptor genotypes and colon cancer: gene–gene and gene–lifestyle interactions. Int J Cancer 122:1611–1617

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathological Physiology, Faculty of Medicine, Masaryk University, University Campus Bohunice, A18, Kamenice 5, 625 00, Brno, Czech Republic

    Anna Vašků & Julie Bienertová-Vašků

  2. 1st Department of Surgery, St. Ann’s Faculty Hospital, Faculty of Medicine, Masaryk University Brno, Pekařská 53, 656 91, Brno, Czech Republic

    Jiří Vokurka

  3. Department of Surgery, Faculty Hospital Bohunice, Faculty of Medicine, Masaryk University Brno, Jihlavská 20, 625 00, Brno, Czech Republic

    Jiří Vokurka

  4. Department of Pathological Physiology, Faculty of Medicine, Masaryk University, University Campus Bohunice, Kamenice 5, 625 00, Brno, Czech Republic

    Anna Vašků

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  1. Anna Vašků
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Correspondence to Anna Vašků.

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Vašků, A., Vokurka, J. & Bienertová-Vašků, J. Obesity-related genes variability in Czech patients with sporadic colorectal cancer: preliminary results. Int J Colorectal Dis 24, 289–294 (2009). https://doi.org/10.1007/s00384-008-0553-6

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  • DOI: https://doi.org/10.1007/s00384-008-0553-6

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