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


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.
Vasků
Anna
A
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, University Campus Bohunice, A18, Kamenice 5, 625 00 Brno, Czech Republic. avasku@med.muni.cz
Vokurka
Jirí
J
Bienertová-Vasků
Julie
J
D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000150:complications* / Q000235:genetics*; D018153:Czech Republic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D020738:Leptin / Q000235:genetics; D008297:Male; D009765:Obesity / Q000150:complications* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054411:Receptors, Leptin / Q000235:genetics; D044465:White People / Q000235:genetics*
D015850:Interleukin-6; D020738:Leptin; D054411:Receptors, Leptin; D000808:Angiotensinogen