Interactive potential of genetic polymorphism in Xenobiotic metabolising and DNA repair genes for predicting lung cancer predisposition and overall survival in North Indians

Purpose Our goal was to determine whether single nucleotide polymorphisms (SNPs) in DNA repair genes influence the clinical outcome of pancreatic cancer. Patients and Methods We evaluated 13 SNPs of eight DNA damage response and repair genes in 92 patients with potentially resectable pancreatic adenocarcinoma. All patients were treated with neoadjuvant concurrent gemcitabine and radiotherapy with or without a component of induction gemcitabine/cisplatin at The University of Texas M.D. Anderson Cancer Center (Houston, TX) from February 1999 to August 2004 and observed through August 2005. Response to the pretreatment was assessed by evaluating time to tumor progression and overall survival. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype. Results The RecQ1 A159C, RAD54L C157T, XRCC1 R194W, and ATM T77C genotypes had a significant effect on the overall survival with log-rank P values of .001, .004, .001, and .02, respectively. A strong combined effect of the four genotypes was observed. Patients with none of the adverse genotypes had a mean survival time of 62.1 months, and those with one, two, or three or more at-risk alleles had median survival times of 27.5, 14.4, and 9.9 months, respectively (log-rank P < .001). There is a significant interaction between the RecQ1 gene and other genotypes. All four genes except XRCC1 remained as independent predictors of survival in multivariate Cox regression models adjusted for other clinical predictors. Conclusion These observations support the hypothesis that polymorphic variants of DNA repair genes affect clinical prognosis of patients with pancreatic cancer.

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Use a survival model to correlate single-nucleotide polymorphisms of DNA repair genes with radiation dose–response in patients with non-small cell lung cancer

Radiotherapy and Oncology ◽

10.1016/j.radonc.2015.07.024 ◽

2015 ◽

Vol 117 (1) ◽

pp. 77-82 ◽

Cited By ~ 6

Author(s):

Jian-Yue Jin ◽

Weili Wang ◽

Randall K. Ten Haken ◽

Jie Chen ◽

Nan Bi ◽

...

Keyword(s):

Lung Cancer ◽

Dna Repair ◽

Radiation Dose ◽

Dose Response ◽

Small Cell ◽

Dna Repair Genes ◽

Nucleotide Polymorphisms ◽

Small Cell Lung ◽

Single Nucleotide ◽

Repair Genes

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Associations between polymorphisms in DNA repair genes and TP53 mutations in non-small cell lung cancer

Lung Cancer ◽

10.1016/j.lungcan.2010.10.023 ◽

2011 ◽

Vol 73 (1) ◽

pp. 25-31 ◽

Cited By ~ 7

Author(s):

Sukki Cho ◽

Min Jung Kim ◽

Yi Young Choi ◽

Seung Soo Yoo ◽

Won Kee Lee ◽

...

Keyword(s):

Lung Cancer ◽

Dna Repair ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Dna Repair Genes ◽

Small Cell Lung ◽

Tp53 Mutations ◽

Repair Genes

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Polymorphisms of DNA-repair genes associated with clinical outcome in metastatic breast cancer (MBC) patients treated with gemcitabine/cisplatin (GC) (California Cancer Consortium)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.675 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 675-675

Author(s):

M. A. Gordon ◽

W. Zhang ◽

D. Yang ◽

D. Spicer ◽

J. Doroshow ◽

...

Keyword(s):

Overall Survival ◽

Dna Repair ◽

Clinical Outcome ◽

Tumor Progression ◽

Tumor Response ◽

Dna Repair Genes ◽

Repair Capacity ◽

Repair Enzymes ◽

Repair Genes ◽

Time To Tumor Progression

675 Background: DNA repair enzymes may play an important role in determining efficacy of chemotherapy in MBC. In particular, GC combination therapy may be dependent on activity of DNA repair enzymes in host cells, since cisplatin acts by inducing DNA damage. Cancer cells with increased DNA repair capacity may be resistant to GC, and specific genes may be responsible for this increased repair capacity. We examined whether polymorphisms in genes related to DNA repair were associated with clinical outcome in MBC patients treated with GC, enrolled in a parent phase II clinical trial (Ph II-14 A & B). Methods: Fifty-five patients with MBC were evaluated. Patients received the following regimen: 25 mg/m2 cisplatin on days 1–4; 1000 mg/m2 gemcitabine on days 2 and 8 of 21-day cycle. Thirteen polymorphisms in 10 cancer-related genes were tested for association with overall survival, time to tumor progression, and tumor response using a PCR RFLP based assay. Results: Of 55 patients evaluated, there were 17 responders (31%) and 33 non-responders (60%). Five patients (9%) inevaluable for response. Of 33 non-responders, 15 had stable disease, 18 had progressive disease. Median survival: 11.7 months with median follow-up 32.4 months for 4 patients alive at time of analysis. Median progression-free survival: 4.2 months. XPD Lys751Gln polymorphism was associated with overall survival and time to tumor progression (p=0.0003, p=0.006, respectively, log-rank test). Thirty-five patients carried Lys/Lys genotype, of which 29% resopnded. Fourteen patients carried Lys/Gln genotype, of which 54% resopnded. Five patients carried Gln/Gln genotype, with no responders. XRCC3 Thr241Met polymorphism was associated with time to tumor progression and tumor response (p=0.03, p=0.002, respectively). Eighteen patients had Met/Met genotype, of which 47% responded. Twenty-six patients had heterozygous genotype, of which 17% responded. Five patients had homozygous Thr/Thr, of which 100% responded. Conclusions: Our results suggest that polymorphisms in DNA repair genes XPD and XRCC3 may be important markers in predicting clinical outcome in MBC patients treated with GC. Supported by the following NCI grant: N01 CM1701. [Table: see text]

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