Effects of genetic polymorphisms of ERCC1, XRCC1, GSTP1, ABCB1, and CYP on prognosis of patients with non-small cell lung cancer receiving platinum-based chemotherapy

Abstract

Aim: Lung cancer has the greatest mortality rates among both men and women and is the primary cause of cancer-related fatalities globally. The effectiveness of chemotherapy as a treatment for lung cancer varies greatly from patient to patient. Genetic factors affect the effectiveness of chemotherapy. Material and Methods: Age of patients, types of lung cancer, smoking status, genetic profiles (ERCC-C8062A, ERCC-G28152A, GSTP1-A313G, ABCB1-C1236T, ABCB1-C3435T, CYP3A52B, CYP3A41B), clinical stages of cancer, and treatment were evaluated by Kaplan-Meier estimates, and a Cox regression model was conducted to assess survival probability and hazard of death of different groups. Results: Cox regression analysis revealed that ABCB1-C1236T and ABCB1-C3435T wild and heterozygous alleles, smoking, adenocarcinoma, and other types of cancer were used for predicting progression time in advanced-stage lung cancer patients. However, no variables were found to be significant predictors of progression time in early-stage lung cancer patients. Conclusions: Overall, our results imply that genetic variables may play a substantial influence in the rate of lung cancer progression and emphasize the need for tailored medication in the treatment of this disease. Discovering genetic markers that can predict the advancement time of lung cancer could assist clinicians in customizing treatment approaches for individual patients and improving the prognosis for people afflicted with this dreadful disease.

Keywords

• Lung cancer
• NSCLC
• Chemotherapy
• Polymorphism
• Platinum

Supporting Institution

The authors received no financial support for the research and/or authorship of this article.

Project Number

none

Ethical Statement

Ethical approval was obtained from the Pamukkale University Non-Interventional Clinical Research Ethics Committee (Decision No: E-60116787-020-443429, dated October 31, 2023).

ERCC1, XRCC1, GSTP1, ABCB1 ve CYP genetik polimorfizmlerinin platin tabanlı kemoterapi alan küçük hücreli dışı akciğer kanseri hastalarının prognozu üzerine etkileri

Abstract

Amaç: Akciğer kanseri, hem erkekler hem de kadınlar arasında en yüksek ölüm oranlarına sahip ve küresel olarak kanserle ilişkili ölümlerde birinci sırada yer almaktadır. Kemoterapinin akciğer kanseri tedavisindeki verimliliği, genetik faktörlerin kemoterapinin etkinliğini etkilemesinden dolayı hastadan hastaya büyük ölçüde değişiklik göstermektedir. Gereç ve Yöntemler: Hastaların yaşı, akciğer kanseri tipleri, sigara içme durumu, genetik profili (ERCC-C8062A, ERCC-G28152A, GSTP1-A313G, ABCB1-C1236T, ABCB1-C3435T, CYP3A52B, CYP3A41B), kanserin klinik evreleri ve tedavi yöntemleri Kaplan-Meier tahminleri ve farklı grupların sağ kalma olasılıkları ve ölüm tehlikesini değerlendirmek amacıyla yapılan Cox regresyon modeli ile değerlendirildi. Bulgular: Progresyon süresini tahmin etmek için ileri evre akciğer kanseri hastalarında ABCB1-C1236T ve ABCB1-C3435T yabanıl ve heterozigot alelleri, sigara içme, adenokarsinom ve diğer kanser türlerinin kullanılabileceği, Cox regresyon analizi ile ortaya konulmuştur. Ancak, erken evre akciğer kanseri hastalarında progresyon süresini tahmin etmek için anlamlı bir değişken bulunamamıştır. Sonuçlar: Genel olarak, sonuçlarımız genetik değişkenlerin akciğer kanseri ilerleme oranında önemli bir etkiye sahip olabileceğini ve bu hastalığın tedavisinde kişiye özel ilaç tedavisine olan ihtiyacı vurgulamaktadır. Akciğer kanserinin progresyon süresini tahmin edebilecek genetik belirteçlerin keşfedilmesi, klinisyenlerin bireysel hastalar için tedavi yaklaşımlarını özelleştirmelerine ve bu ciddi hastalıktan muzdarip kişilerin prognozunu iyileştirmelerine yardımcı olabilir.

Keywords

• Akciğer kanseri
• NSCLC
• Kemoterapi
• Polimorfizm
• Platin

Project Number

none

References

1. Thandra KC, Barsouk A, Saginala K, Aluru JS, Barsouk A. Epidemiology of lung cancer. Contemp Oncol (Poznan, Poland) 2021; 25: 45–52.
2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74: 229–63.
3. Zhang C, Xu C, Gao X, Yao Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics 2022; 12: 2115–32.
4. Khan MA, Vikramdeo KS, Sudan SK, Singh S, Wilhite A, Dasgupta S et al. Platinum-resistant ovarian cancer: From drug resistance mechanisms to liquid biopsy-based biomarkers for disease management. Semin Cancer Biol 2021; 77: 99–109.
5. Turan C, Kantar M, Aktan Ç, Kosova B, Orman M, Bilgen C et al. Cisplatin ototoxicity in children: risk factors and its relationship with polymorphisms of DNA repair genes ERCC1, ERCC2, and XRCC1. Cancer Chemother Pharmacol 2019; 84: 1333–8.
6. Kim W, Cho Y-A, Kim D-C, Lee K-E. Association between Genetic Polymorphism of GSTP1 and Toxicities in Patients Receiving Platinum-Based Chemotherapy: A Systematic Review and Meta-Analysis. Pharmaceuticals 2022; 15.
7. Loos NHC, Beijnen JH, Schinkel AH. The inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins. Biomed Pharmacother 2023; 162: 114636.
8. Engle K, Kumar G. Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update. Eur J Med Chem 2022; 239: 114542.

9. Park DJ, Zhang W, Stoehlmacher J, Tsao-Wei D, Groshen S, Gil J et al. ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy. Clin Adv Hematol Oncol 2003; 1: 162-6.
10. Alves AA, Laurinho K, Franco FC, de Araujo Nascimento F, Nunes HF, de Melo E Silva D. The Incidence of the XRCC1 rs25487 and PON1 rs662 Polymorphisms in a Population from Central Brazil: Patterns in an Area with a High Level of Agricultural Activity. Biochem Genet 2023.
11. Karagur ER, Demiray A, Karagenc N, Elver E, Tokgun O, Yaren A et al. Is there an advantage of monitoring via exosome-based detection of EGFR mutations during treatment in non-small cell lung cancer patients? Genetika 2023; 55: 89–93.
12. Butkiewicz D, Drosik A, Suwiński R, Krześniak M, Rusin M, Kosarewicz A et al. Influence of DNA repair gene polymorphisms on prognosis in inoperable non-small cell lung cancer patients treated with radiotherapy and platinum-based chemotherapy. Int J Cancer 2012; 131: 1100-8.
13. Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006; 355: 983–91.
14. Liu W, Wang Y, Luo J, Yuan H, Luo Z. Genetic Polymorphisms and Platinum-Based Chemotherapy-Induced Toxicities in Patients With Lung Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2019; 9: 1573.
15. Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 2001; 70: 189–99.
16. Zhong J, Guo Z, Fan L, Zhao X, Zhao B, Cao Z et al. ABCB1 polymorphism predicts the toxicity and clinical outcome of lung cancer patients with taxane-based chemotherapy. Thorac Cancer 2019; 10: 2088–95.
17. Hecht SS. Lung carcinogenesis by tobacco smoke. Int J Cancer 2012; 131: 2724–32.
18. Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med 2008; 359: 1367–80.