Kolorektal Kanserlerde Sigara Kullanımı ve Lenf Nodu Metastazının Sağkalım ile İlişkisi

Year 2022, Volume: 6 Issue: 2, 126 - 131, 30.08.2022

Sevda Yeşim Özdemir Murat Çağ Yusuf Özkul

https://doi.org/10.46332/aemj.963344

Abstract

Amaç: En yaygın kanser türlerinden biri olan kolorektal kanserler ölüm oranı açısından da ilk sıralarda yer almaktadır. Bu oranı azaltmak için sıklık ve risklerin iyi tanımlanması önem taşır. KRK’da sigara kullanımı gibi birçok faktör polip veya kolorektal kanser gelişme olasılığını artırdıkları için risk faktörü olarak kabul edilir. Bu çalışmada, Yeni Nesil Dizileme analizi ile 18 gendeki germline mutasyonları incelenmiş olup kolon kanserlerinde genetik etki ile sigaranın oynadıkları rol karşılaştırıldı.

Araçlar ve Yöntem: Erciyes Üniversitesi Tıbbi Onkoloji Anabilim Dalı'nda 2010-2018 yılları arasında izlenen toplam 50 kolon kanserli hastaya ait parafin bloklar retrospektif bu çalışmaya dahil edildi. Yeni nesil dizileme sonrası SOPHiA DDM® (Saint-Sulpice, İsviçre) biyoinformatik programında gerçekleştirildi. Çalışmanın verileri IBM SPSS Statistics Standard Concurrent User V 25 (IBM Corp, Armonk, New York, USA) istatistik programıyla değerlendirildi. 

Bulgular: Çalışmada uzak organ metastazı olan hastalarda, metastazı olmayan hastalara göre APC ve MUTYH genetik mutasyonlarının varlığı 3.083 kat daha fazla görüldü ve bu hastalar 6.364 kat daha fazla TP53 genetik mutasyonu sergiledi. nAPC, MUTYH ve MSH2 ile tümör evresi arasında bir ilişki tespit edildi. Sigara içme durumu ile uzak organ metastazı olan ve olmayan hastalar arasında
istatistiksel olarak önemli bir ilişki saptanmadı. Ayrıca Gen mutasyon sayısı ile sağkalım arasında istatistiksel olarak önemli bir ilişki saptanmadı.

Sonuç: APC ve MUTYH ‘nin genel sağkalım üzerinde kötü bir etkiye sahip olduğu belirlendi. Hastaların derece, evre ve LNM ile genel sağ kalım durumları arasında anlamlı bir ilişki olduğu belirlendi. Yaş ve grade ile beklenen survey arasında, uzak organ metastazı olan hastalarda anlamlı ilişki bulundu

Keywords

kolorektal kanserler (KRK), metastaz, sağ kalım, sigara

Supporting Institution

YOK

The Relationship of Smoking and Lymph Node Metastasis with Survival in Colorectal Cancers

Abstract

Purpose: Colorectal cancers, which are one of the most common types of cancer, take the first ranks in terms of mortality. Various factors, such as smoking, are considered risk factors in CRC. In this study, germline mutations in 18 genes were examined by Next Generation Sequencing analysis and the role played by smoking and genetic effects in colon cancers were compared. 

Materials and Methods: In this retrospective study, paraffin blocks of 50 patients with colon cancer that were followed up in between 2010 and 2018 were included. The bioinformatics program SOPHiA DDM® was used for next-generation sequencing. The data of the study were evaluated by the IBM SPSS Statistics Standard Concurrent User V 25 (IBM Corp, Armonk, New York, USA) statistics program.

Results: In the study, it was concluded that the presence of APC and MUTYH genetic mutations was 3.083 times more common in patients with distant organ metastasis compared to patients without metastasis and these patients exhibited 6.364 times more TP53 genetic mutations. Also, a relationship was found between APC, MUTYH, and MSH2 and tumor stage. There was no statistically significant relationship between smoking status and Colon Ca patients with and without distant organ metastasis. 

Conclusion: APC and MUTYH were found to have a bad effect on overall survival. It was determined that there was a significant relationship between the patients' grade, stage, and overall survival status. A significant relationship was found between the expected survey of age and grade in patients with distant organ metastasis.

Keywords

colorectal cancers (CRC), metastasis, survival, smoking

References

• 1. Brody H. Colorectal cancer. Nature 2015;521(7551):1.
• 2. Schrembs P, Martin B, Anthuber M, Schenkirsch G, Markl B. The prognostic significance of lymph node size in node-positive colon cancer. PLoS One. 2018;13(8):e0201072.
• 3. Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6:479-507.
• 4. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546-1558.
• 5. Pearlman R, Frankel WL, Swanson B ve ark. Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer. JAMA Oncol. 2017;3(4):464-471.
• 6. Giovannucci E. Modifiable risk factors for colon cancer. Gastroenterol Clin North Am. 2002;31(4):925-943.
• 7. Amri R, Bordeianou LG, Patricia Sylla P, Berger DL. Does active smoking induce hematogenous metastatic spread in colon cancer? Am J Surg. 2015;210(5):930-932.
• 8. Riihimaki M, Thomsen H, Sundquist K, Hemminki K. Colorectal cancer patients: what do they die of?. Frontline Gastroenterol. 2012;3(3):143-149.
• 9. Javier MU, Foncillas JG. Obesity and colorectal cancer: molecular features of adipose tissue. J Transl Med. 2016;14(1):21.
• 10. Botteri E, Iodice S, Bagnardi V, Raimondi S, Lowenfels AB, Maisonneuve P. Smoking and colorectal cancer: a meta-analysis. JAMA. 2008;300(23):2765-2778.
• 11. Cross AJ, Boca S, Freedman ND ve ark. Metabolites of tobacco smoking and colorectal cancer risk. Carcinogenesis. 2014;35(7):1516-1522.
• 12. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol.2010;17(6):1471-1474.
• 13. Luo D, Liu Q, Yu W ve ark. Prognostic value of distant metastasis sites and surgery in stage IV colorectal cancer: a population-based study. Int J Colorectal Dis. 2018;33(9):1241-1249.
• 14. Sauer R, Becker H, Hohenberger W ve ark. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731-1740.
• 15. Howlader N, Mariotto AB, Besson C ve ark. Cancerspecific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era. Cancer. 2017;123(17):3326-3334.
• 16. Johnson PM, Porter GA, Ricciardi R, Baxter NN. Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer. J Clin Oncol. 2006;24(22):3570-3575.
• 17. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 2009;361(25):2449-2460.
• 18. Fang LT, Lee S, Choi H ve ark. Comprehensive genomic analyses of a metastatic colon cancer to the lung by whole exome sequencing and gene expression analysis. Int J Oncol. 2014;44(1):211-221.
• 19. Lee SH, Jung SH, Kim TM ve ark. Whole-exome sequencing identified mutational profiles of highgrade colon adenomas. Oncotarget. 2017;8(4):6579-6588.
• 20. Li W, Qiu T, Zhi W ve ark. Colorectal carcinomas with KRAS codon 12 mutation are associated with more advanced tumor stages. BMC Cancer. 2015;15(1):340.
• 21. Kayhanian H, Goode E, Sclafani F ve ark. Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer: A Retrospective Matched CaseControl Study. Clin Colorectal Cancer. 2018;17(1):69-76.
• 22. Brannon AR, Vakiani E, Sylvester BE ve ark. Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions. Genome Biol. 2014;15(8):454.
• 23. Nakayama M, Oshima M. Mutant p53 in colon cancer. J Mol Cell Biol. 2019;11(4):267-276.
• 24. Amri R, Bordeianou L, Sylla P, Berger D. Does active smoking induce hematogenous metastatic spread in colon cancer? Am J Surg. 2015;210(5):930-932.