Leptin ve Leptin Reseptörü Gen Varyantları ile Kolorektal Kanser Arasındaki İlişki Üzerine Bir Çalışma / Examining the Relationship Between Colorectal Cancer and Gene Polymorphisms of Leptin and Leptin Receptors

Neslihan Korkmaz, Adnan Selim Kimyon, Esra Ermiş, Tuba Edgünlü, Erkan Arpacı, Hüseyin Engin, Sevim Karakaş Çelik

Özet


Özet
Kolorektal kanser; kalın bağırsak ve rektumda görülen malign oluşumlardır. Etyopatolojisi henüz net olarak aydınlatılmamış olan çevresel ve genetik faktörlerin etkili olduğu bilinen bir hastalıktır. Çalışmamızda, adipositler tarafından salgılanan enerji dengesi, besin alınımın düzenlenmesi ve besin emiliminde önemli rol oynayan leptin (LEP) ve leptin reseptörlerine (LEPR) ait gen polimorfizimlerinin kolorektal kanser ile ilişkisini araştırmayı amaçladık. Çalışmamıza 55 kolorektal kanseri tanısı almış hasta ve 54 sağlıklı birey dahil edildi. Bireylerden alınan kanlardan DNA izolasyon kiti yöntemiyle DNA lar elde edildi. LEP rs7799039 ve LEPR rs1137101 gen polimorfizmleri PCR-RFLP yöntemi ile analiz edildi. Elde edilen veriler istatistiksel olarak değerlendirildiğinde, LEPR rs1137101 gen polimorfizmine ait AG genotipinin hastalık riskini 2.6 kat artırdığı tespit edildi (p<0.05). Ancak, kolorektal kanserli olgular ve LEP rs7799039 geni arasında anlamlı bir ilişki bulunamadı (p>0.05). Çalışmamız sonucunda LEPR rs7799039 gen polimorfizminin kolorektal kanser etyopatogenezinde etkili olabileceği tespit edilmiştir. Sonraki aşamalarda, daha geniş popülasyonlarda ve genlere ait ekspresyon düzeyleri de araştırılması uygun olacaktır.
Anahtar Kelimeler: Kolorektal Kanser, Leptin, Leptin Reseptörü, Polimorfizm

Abstract
Colorectal cancer is defined as malignant occurrences observed in the large intestine and rectum. It is a disease whose etiopathology has known to be influenced by environmental and genetic factors that are not yet clearly understood. We aimed to investigate the relationship between colorectal cancer and gene polymorphisms of leptin (LEP) and leptin receptors (LEPR), which play an important role in regulation of nutrient uptake and regulation of nutrient uptake and energy balance secreted by adipocytes. The study included 55 patients with colorectal cancer and 54 healthy individuals. DNA was obtained from the blood of individuals by DNA isolation kit method. LEP rs7799039 and LEPR rs1137101 gene polymorphisms were analyzed by PCR-RFLP method. The statistical analysis of the results shows that AG genotype of LEPR rs1137101 gene polymorphism was found to increase the risk of disease 2.6 times (p <0.05). However, no significant correlation was found between colorectal cancer and LEP rs7799039 gene polymorphism (p> 0.05). As a result of our study, it was determined that LEPR rs7799039 gene polymorphism may be effective in the etiopathogenesis of colorectal cancer. As a further study, these gene expression levels should be investigated in large populations.
Keywords: Colorectal Cancer, Leptin, Leptin Receptor, Polymorphism

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Referanslar


Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917.

Ahima RS, Flier JS. Leptin. Annu Rev Physiol. 2000;62:413–37.

Ogunwobi, Olorunseun O., Ian LP Beales. The anti-apoptotic and growth stimulatory actions of leptin in human colon cancer cells involves activation of JNK mitogen activated protein kinase, JAK2 and PI3 kinase/Akt. Int J Colorectal Dis. 2007; 22(4):401-9.

Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells. Gastroenterology. 2001;121(1):79-90.

Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263-71.

Nordström V, Willershäuser M, Herzer S, et al. Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis. PLoS Biol. 2013;11(3):e1001506.

Ahima RS, Flier JS. Leptin. Annu Rev Physiol. 2000;62:413-37.

Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev 2007;16: 2533–47.

Nam SY, Kim BC, Han KS, et al. Abdominal visceral adipose tissue predicts risk of colorectal adenoma in both sexes. Clin Gastroenterol Hepatol 2010;8: 443–450 e441–442.

Amemori S, Ootani A, Aoki S, et al. Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. Am J Physiol Gastrointest Liver Physiol 2007;292: G923–9.

Brabant G, Horn R, von zur Mühlen A, et al. Free and protein bound leptin are distinct and independently controlled factors in energy regulation. Diabetologia. 2000;43(4):438-42.

Donahue RP, Prineas RJ, Donahue RD, et al. Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study. Diabetes Care. 1999;22(7):1092-6.

Marik PE. Leptin, obesity, and obstructive sleep apnea. Chest. 2000;118(3):569-71.

Hager J, Dina C, Francke S, et al. A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Nat Genet. 1998;20(3):304-8.

Pechlivanis S, Bermejo JL, Pardini B, et al. Genetic variation in adipokine genes and risk of colorectal cancer. Eur J Endocrinol. 2009;160(6):933–40.

Slattery ML, Wolff RK, Herrick J, Caan BJ, Potter JD. Leptin and leptin receptor genotypes and colon cancer: Gene–gene and gene–lifestyle interactions. Int J Cancer. 2008 Apr 1;122(7):1611-7.

Liu P, Shi H, Liu R, et al. Lack of association between LEPR Q223R polymorphisms and cancer susceptibility: evidence from a meta-analysis. J BUON. 2014 Jul-Sep;19(3):855-62.

Partida-Perez M, de la Luz Ayala-Madrigal M, Peregrina-Sandoval J, et al. Association of LEP and ADIPOQ common variants with colorectal cancer in Mexican patients. Cancer Biomark. 2010;7(3):117–21.

Pechlivanis S, Bermejo JL, Pardini B, et al. Genetic variation in adipokine genes and risk of colorectal cancer. Eur J Endocrinol. 2009;160(6):933-40.


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