Biomedical subjects

Sang Yoon Kim

Publications and source records attributed to Sang Yoon Kim.

At least 19 recordsLinked to original sources

PubMed2007

Utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging in the preoperative staging of head and neck squamous cell carcinoma.

The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) has been reported to be more accurate than CT or PET alone in a preoperative setting. We compared the diagnostic utility of preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63 underwent combined PET/CT with all receiving CT/MRI. These preoperative PET, PET/CT, and CT/MRI results were reviewed and their accuracies were compared in patients in whom diagnosis was confirmed histopathologically. Age, sex, primary sites and stage, and nodal involvement were comparable between two groups. The accuracy of PET and PET/CT for detecting primary tumors and cervical metastases was comparable, but significantly higher than that of CT/MRI (98%-97% vs. 86-88% for primary; 92%-93% vs. 85%-86% for neck on a level-by-level basis; P<.05). PET and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4 (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may not yield significantly improved diagnostic accuracy in patients with HNSCC. Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need for conventional imaging and pathologic staging based on primary resection and neck dissection.

Adult↗

PubMed2007

In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications.

The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to evaluate various self-assembled nanoparticles as candidates to shuttle radionuclide and/or drugs into tumors and to investigate the mechanisms underlying the tumor targeting with self-assembled nanoparticles. By combining different hydrophobic moieties and hydrophilic polymer backbones, various self-assembled nanoparticles were prepared, and their in vivo distributions in tumor-bearing mice were studied by radionuclide imaging. One type of nanoparticles (fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles) exhibited highly selective tumoral localization. Scintigraphic images obtained 1 day after the intravenous injection of FGC nanoparticles clearly delineated the tumor against adjacent tissues. The mechanisms underlying the tumor targeting with self-assembled nanoparticles were investigated in terms of the physicochemical properties of nanoparticles and tumor microenvironments. FGC nanoparticles were preferentially localized in perivascular regions, implying their extravasation to tumors through the hyperpermeable tumor vasculature. The magnitude and pattern of tumoral distribution of self-assembled nanoparticles were influenced by several key factors--(i) in vivo colloidal stability: nanoparticles should maintain their intact nanostructures in vivo for a long period of time, (ii) particle size, (iii) intracellular uptake of nanoparticle: fast cellular uptake greatly facilitates the tumor targeting, (iv) tumor angiogenesis: pathological angiogenesis permits access of nanoparticles to tumors. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis, so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.

Animals↗

PubMed2006

Antiangiogenic effect of bile acid acylated heparin derivative.

PURPOSE: Chemically modified heparin-DOCA was prepared and found to have markedly lower anticoagulant activity than heparin. In the present study, we elucidated the antiangiogenic and antitumoral activities of heparin-DOCA derivative. METHODS: To evaluate the antiangiogenic and antitumoral effects of heparin-DOCA, capillary-like tube formation assay, Matrigel plug assay in vivo, western blotting for FGFR phosphorylation, ERK and p38 MAPK activities, tumor growth of SCC in vivo and immunostaining of blood vessels in tumor tissues were performed. RESULTS: Heparin-DOCA inhibited capillary-like tubular structures of endothelial cells and bFGF-induced neovascularizations in Matrigel plug assays. Signaling experiments showed that heparin-DOCA significantly inhibited angiogenesis by suppressing the phosphorylation of FGFR and its downstream signal pathways (ERK and p38 MAPK activities). The antiangiogenic activity of this heparin derivative was found to be closely associated with antitumoral activity in a mouse model. In addition, histological evaluations supported the inhibitory effect of heparin-DOCA on blood vessel formation in tumor tissues. CONCLUSION: Heparin-DOCA derivative exerted a significant antitumoral effect by inhibiting angiogenesis resulting from the disruption of FGF/FGFR and its downstream signal pathways, and could be applied to treat various angiogenic diseases.

Angiogenesis Inhibitors↗

PubMed2006

F-18 FDG-PET as a routine surveillance tool for the detection of recurrent head and neck squamous cell carcinoma.

In order to determine the efficacy and proper timing of routine PET scans for surveillance of recurrent head and neck squamous cell carcinoma (HNSCC), we evaluated the diagnostic performance of routine PET scans in relation to time interval from completion of treatment. Amongst 206 retrospectively evaluated post-treatment PET scans of 159 patients with HNSCC, 156 were performed for routine surveillance in subclinical cases. Diagnostic performance of PET scan and follow-up outcome were evaluated in relation to the time interval (2-6months, 6-12months, 12-24months, and >24months) of PET scan from the completion of treatment. Overall sensitivity and NPV of these PET scans for recurrence were 92.5% and 94.8%, compared with 55.0% and 76.9% for conventional evaluation methods. In the 156 routine scans, the diagnostic sensitivity, specificity, and NPV for locoregional recurrence were 90%, 91% and 97%, respectively, and the values for distant metastases and second primary cancers were 100%, 97% and 100%, respectively. The diagnostic accuracy of routine PET scans was not significantly altered by the time interval. Most (97%) of true negative cases on routine PET scans had no recurrence during a median 14months follow-up. PET scan may be a useful tool in routine surveillance for detection of recurrence in subclinical patients. For routine surveillance, the initial PET scan should be performed within 6months after completion of treatment and the proper timing of next routine PET scan for subclinical patient with initial negative PET result might be 1year after initial PET scan.

Adult↗

PubMed2006

Clinical significance of intrathoracic lesions detected by 18F-fluorodeoxyglucose positron emission tomography in the management of patients with head and neck cancer.

Few studies have used positron emission tomography (PET) to identify metastases or simultaneous thoracic malignancies in patients with head and neck cancer (HNC). We retrospectively investigated the role of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting thoracic malignancies in patients with previously untreated HNC. Patients (n=86) with HNC and intrathoracic lesions on PET were divided into those who had abnormal FDG uptake in the mediastinum (n=29), lungs (n=34), or both (n=23). Whole body PET and chest computed tomography (CT) results were blindly reviewed and scored by two observers. The accuracy of FDG PET and CT were drawn from patients in whom diagnosis was confirmed, by histopathology or follow-up imaging, and risk factors for thoracic malignancy were analyzed. Malignancy was suspected in 23 of 86 patients (27%) with FDG uptake. Most of the lesions (83%) with abnormal FDG uptake were benign, with thoracic malignancy confirmed in 15 patients (17%). The overall sensitivity, specificity, and accuracy of FDG PET for intrathoracic malignancy in these patients were 80%, 85%, and 84%, respectively. The likelihood of thoracic malignancy in the HNC patients was associated with high FDG uptake of thoracic lesions. FDG PET may reveal lung and mediastinal malignancies with high accuracy in patients with HNC. The thoracic staging by FDG PET may be helpful in therapeutic planning for these patients.

Adolescent↗

PubMed2006

Cervical sensory preservation during neck dissection.

Although the practice of neck dissection has greatly advanced from radical to function-preserving surgery, the impact of the sensory nerve-preserving neck surgery on the pain and quality of life (QOL) of patients has received little study. We evaluated neck morbidity and its impact on QOL associated with selective or modified radical neck dissection with or without preservation of cervical root branches. We conducted a retrospective cohort study comparing 24 patients who had their cervical root branches preserved to 29 patients whose root branches were removed during neck dissection. The spinal accessory nerve was preserved and sex, age, pathologic status, side and extent of neck dissection, and radiotherapy were comparable between groups. The groups were compared based on sensory and motor functions of the neck and shoulder and questionnaires on depression and QOL at follow-up of mean 18.7 (range 12-34) months after surgery. The nerve-preserved patients showed a low incidence and severity of neck and shoulder pain compared to the nerve-removed subjects (p<.05). Loss of sensation was more frequently experienced in the nerve-removed group on the earlobe and the lateral neck of the operated side (p<.05). Depression and QOL scores were higher in the nerve-removed group and significantly correlated with pain intensity. Preservation of the cervical root branches reduces postoperative pain as well as permanent anesthetic areas of the neck. This may also improve the mental state and QOL of patients undergoing neck dissection.

Adult↗

PubMed2006

N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs: endocytosis, exocytosis and drug release.

Nano-sized vesicular systems (nanoparticles), ranging from 10 nm to 1000 nm in size, have potential applications as drug delivery systems. Successful clinical applications require the efficient intracellular delivery of drug-loaded nanoparticles. Here we describe N-acetyl histidine-conjugated glycol chitosan (NAcHis-GC) self-assembled nanoparticles as a promising system for intracytoplasmic delivery of drugs. Because N-acetyl histidine (NAcHis) is hydrophobic at neutral pH, the conjugates formed self-assembled nanoparticles with mean diameters of 150-250 nm. In slightly acidic environments, such as those in endosomes, the nanoparticles were disassembled due to breakdown of the hydrophilic/hydrophobic balance by the protonation of the imidazole group of NAcHis. Cellular internalization and drug release of the pH-sensitive self-assembled nanoparticles were investigated by flow cytometry and confocal microscopy. NAcHis-GC nanoparticles internalized by adsorptive endocytosis were exocytosed or localized in endosomes. The amount of exocytosed nanoparticles was dependent on the pre-incubation time prior to removal of free nanoparticles from the culture media. Flow cytometry and confocal microscopy showed that NAcHis-GC nanoparticles released drugs into the cytosol and cell cycle analysis demonstrated that paclitaxel-incorporated NAcHis-GC nanoparticles were effective in inducing arrest of cell growth.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Heparin-deoxycholic acid chemical conjugate as an anticancer drug carrier and its antitumor activity.

A chemically modified heparin-DOCA (HD) conjugate was developed as a drug carrier for cancer therapy. HD conjugate was found to have markedly low anticoagulant activity and to form self-assembled nanoparticles in aqueous condition. We observed that HD conjugate prevented squamous cell carcinoma (SCC) and human umbilical vascular endothelial cell (HUVEC) proliferation during BrdU incorporation assays. Here, we prepared doxorubicin-loaded heparin nanoparticles by entrapping doxorubicin into the amphiphilic HD conjugate by physical interaction and characterized the properties of these nanoparticles using Dynamic Light Scattering (DLS) and Atomic Force Microscope (AFM). In this study, doxorubicin-loaded heparin nanoparticles were designed to improve the antitumor effects of nano-sized particles (range of 180 to 210 nm) at high drug-loading efficiencies in the range 64% to 96%. These doxorubicin-loaded heparin nanoparticles displayed sustained drug release patterns. It was confirmed in vivo toxicity studies that HD conjugate did not induce unexpected side effects and that DHN 20 was safer than free DOX. An in vivo study showed that HD conjugate, doxorubicin and DHN 20 (one of doxorubicin-loaded heparin nanoparticles) induced tumor volume reductions of 43%, 56% and 74%, respectively, relative to the saline treated control. These results suggest that the drug-entrapped with heparin nanoparticles might provide a novel therapy for SCC.

Animals↗

PubMed2006

Chemopreventive efficacy of all-trans-retinoic acid in biodegradable microspheres against epithelial cancers: results in a 4-nitroquinoline 1-oxide-induced oral carcinogenesis model.

Retinoids are known to suppress carcinogenesis in various epithelial tissues. Among them, all-trans-retinoic acid (atRA) is recognized as one such active retinoid. However, despite the known anticarcinogenic activity of atRA, it exhibits its short plasma half-life during repeated oral administration due to the "acute retinoid resistance" in the liver. This has been the major limitation in clinical applications of atRA. Therefore, in order to render atRA more suitable for clinical uses, sustained delivery of atRA using biodegradable microspheres is suggested in this study. When 50 mg atRA/kg of atRA-loaded microspheres were subcutaneously administered to rats once, the atRA concentration in plasma was maintained around 6.5 ng/ml for 7 weeks, with only minor signs of toxicity. When the chemopreventive efficacy of atRA-loaded microspheres was evaluated using a model of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in F344 rats, a single injection of atRA-loaded microspheres significantly suppressed oral carcinogenesis. Additional injections of atRA-loaded microspheres, however, did not indicate further suppression of carcinogenesis.

4-Nitroquinoline-1-oxide↗

PubMed2006

Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma.

PURPOSE: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the "step and shoot" SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. RESULTS: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. CONCLUSION: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

Adult↗

PubMed2006

Expression of Ku80 correlates with sensitivities to radiation in cancer cell lines of the head and neck.

The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells. The purpose of this study was to investigate the relationship between the expression of Ku70/80 and sensitivity to radiation in cancer cell lines of the head and neck. The sensitivity to radiation in various head and neck cancer cell lines (AMC-HN-1 to -9) was analyzed by colony forming assay. Of the nine cell lines examined, the most radiosensitive cell line (AMC-HN-3) and the most radioresistant cell line (AMC-HN-9) were selected for this experiments. The expression of Ku70/80 was examined after irradiation using real time PCR, Western blotting and immunofluorescence in two different cell lines. Cell cycle distribution after irradiation were analysed. A differential radioresponse was demonstrated by expression of Ku70/80 in AMC-HN-3 and AMC-HN-9 cells. While the expression of Ku70 was slightly increased in the radioresistant AMC-HN-9 cell line, the expression of Ku80 was remarkably increased, suggesting a correlation between Ku80 expression and radiation resistance. Overexpression of Ku80 plays an important role in the repair of DNA damage induced by radiation. Ku80 expression may provide an effective predictive assay of radiosensitivity in head and neck cancers.

Antigens, Nuclear↗

PubMed2006

Anti-tumor and anti-metastatic effects of gelatin-doxorubicin and PEGylated gelatin-doxorubicin nanoparticles in SCC7 bearing mice.

The goal of this study was to develop a systemically non-toxic and stable circulation based passive targeting system for efficient anticancer treatment. Gelatin-doxorubicin (GD) and PEGylated gelatin-doxorubicin (PGD) nanoparticles were designed and their feasibilities as an anti-cancer drug were evaluated. The sizes of GD and PGD nanoparticles were about 135 and 250 nm, respectively, and they retained their structures for 2 days in PBS. Both GD and PGD had much lower cytotoxicity in vitro and in vivo than doxorubicin (DOX) at equivalent concentrations. However, PGD significantly inhibited tumor growth compared to the control and DOX treated group, and GD moderately suppressed tumor growth compared with the control but the suppressing effect of GD did not exceed that of DOX. And GD and PGD both remarkably suppressed pulmonary metastasis. We conclude that PGD is a potential cancer therapeutic, due to its excellent anti-tumor and anti-metastatic effects and low systemic toxicity.

Amino Acids↗

PubMed2006

Clinical significance of beta1 integrin expression as a prediction marker for radiotherapy in early glottic carcinoma.

OBJECTIVE: To determine the significance of beta1 integrin expression as a prediction marker for the response to radiotherapy in patients with early glottic carcinoma. STUDY DESIGN: Retrospective study in a tertiary referral center. METHODS: Among the T1/T2 glottic carcinoma patients treated with radiotherapy from 1992 to 2002, 52 had more than 2 years of follow-up and available pretreatment biopsy specimens. The immunohistochemical staining was performed for the assay of beta1 integrin expression, and the staining pattern of each was classified as diffuse, localized, or negative. The associations between the patterns of beta1 integrin expression and clinicopathologic parameters, including response to radiotherapy, involvement of the anterior commissure, and grade of histologic differentiation, were evaluated. RESULTS: After radiotherapy, 42 patients remained tumor free, and 10 patients had recurrent or persistent disease. Six (12%) specimens were negative for beta1 integrin expression, 39 (75%) had a localized staining pattern, and 7 (13%) had a diffuse staining pattern. Recurrence rate was significantly higher in the diffuse group (53%) than in the localized (13%) or negative (17%) groups (P=.023). The pattern of beta1 integrin expression was also closely related to histologic differentiation (P=.008), although the association between response to radiotherapy and histologic differentiation was not significant CONCLUSION: The pattern of expression of beta1 integrin, which has been known as a stem cell marker of the epidermis, may be helpful in predicting the response to radiation in patients with early glottic carcinoma.

Adult↗

PubMed2006

Pectoralis major musculocutaneous flap in oropharyngeal reconstruction: revisited.

BACKGROUND: Free tissue transfer is now favored for head and neck reconstruction following cancer resection. Its success rate is rising with the obvious advances in microsurgery. The pectoralis major musculocutaneous flap, a former workhorse in head and neck reconstruction, has been overlooked and criticized because of its seemingly high rate of complications and cosmetic inferiority, but it is still being used by many surgeons and plays an important role in head and neck reconstruction. METHODS: The authors reviewed 34 pectoralis major musculocutaneous flap cases and 18 free flap cases (12 radial forearm flaps, six rectus abdominis flaps) involving oropharyngeal reconstruction. Flap necrosis, fistula formation, and operative times were compared. The pectoralis major musculocutaneous flap was elevated in true island type with maximal skeletonization of the pectoral branch of the thoracoacromial vessels. RESULTS: In pectoralis major musculocutaneous cases, all defects were reconstructed successfully, with only two cases of partial necrosis that were managed conservatively. Among the free flaps, two resulted in total flap loss and were subsequently replaced with pectoralis major musculocutaneous flaps. Fistula formation did not occur in any case in either group. Mean operative time for pectoralis major musculocutaneous flap preparation was 76 +/- 7 minutes; that for free flap preparation was 145 +/- 11 minutes. CONCLUSIONS: Technical refinements and meticulous procedures minimized necrosis of the pectoralis major musculocutaneous flap and guaranteed the success of the reconstruction. The free flap is an excellent method for oropharyngeal reconstruction, but the refined pectoralis major musculocutaneous flap can also produce acceptable results with minimal complications. In some instances, the pectoralis major musculocutaneous flap is not only an alternative to the free flap but a better choice that presents less risk to the patient.

Female↗

PubMed2006

The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma.

BACKGROUND: The activating BRAF(V600E) mutation is the most common genetic alteration reported in papillary thyroid carcinoma (PTC). While some reports suggest the BRAF(V600E) mutation is associated with factors predicting a poor prognosis and recurrence, this remains a controversial issue. AIM: To determine whether the presence of the BRAF(V600E) mutation is a prognostic indicator for clinical recurrence in low-risk patients with conventional PTC. PATIENTS AND METHODS: The study involved 203 conventional PTC patients who underwent total or near-total thyroidectomy followed by immediate 131I ablation of the remnants. Patients with antithyroglobulin antibodies and those with extracervical metastases at presentation were excluded. DNA was extracted from paraffin-embedded tumour specimens, and the presence of the BRAF(V600E) mutation was evaluated using PCR amplification and direct sequencing. RESULTS: The BRAF(V600E) mutation was found to be present in 149 (73.4%) of 203 patients. The BRAF(V600E) mutation was correlated with male gender (P = 0.006) and with tumour size (P = 0.005). While there appeared to be an association between the BRAF(V600E) mutation and extrathyroid extension, this did not reach statistical significance (P = 0.062). During follow-up of the 203 patients (median 7.3 years; range 0.7-10.0 years), 36 (18%) patients experienced recurrence. While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis. CONCLUSIONS: Although the BRAF(V600E) mutation was found to be associated with a higher clinical recurrence of disease in low-risk conventional PTC patients, it was not an independent predictor.

Adult↗

PubMed2006

Association of the GSTP1 and NQO1 polymorphisms and head and neck squamous cell carcinoma risk.

The GSTP1 and NQO1 have been reported to be associated with an increased risk for smoking related head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to determine the effect of these metabolic gene polymorphisms on the risk of HNSCC. The study population included 294 histologically confirmed HNSCC cases and 333 controls without cancer. Genotyping analysis of the GSTP1 Ile105Val and NQO1 Trp139Arg genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. The Mantel-Haenszel chi2 test was used for statistical analysis. The allele frequencies of the GSTP1 and NQO1 polymorphisms were not statistically significant between cases and controls. In analyzing the association between smoking amounts and genetic polymorphisms, GSTP1 and NQO1 polymorphisms were associated with cigarette smoking amounts in cases. G allele containing genotypes in GSTP1 and T allele containing genotypes in NQO1 were associated with a tobacco dose-dependent increase in risk of HNSCC and these genotype distributions were statistically significant (p<0.05). We found that the GSTP1 105Val allele and NQO1 139Arg allele were associated with tobacco dose-dependent increase in risk of HNSCC. GSTP1 and NQO1 genotype polymorphisms may play an important role in the development of smoking related HNSCC.

Adult↗

PubMed2005

Sarcomatoid salivary duct carcinoma of the larynx.

The sarcomatoid variant is a rare subtype of salivary duct carcinoma that comprises epithelial and sarcomatoid components. The authors present the first reported case of sarcomatoid salivary duct carcinoma occurring in the larynx, which was successfully treated by partial laryngectomy with ipsilateral neck dissection, with no evidence of recurrence after five years. Microscopic analysis revealed a composite epithelial and sarcomatoid tumour. The epithelial component was characterized by papillary proliferation of glandular and ductal structures lined with multilayered epithelial tumour cells. The sarcomatoid component was characterized by pleomorphic spindle cells with cytologic atypia, accompanied by small lymphoid cells, extensive proliferation of blood vessels and focal myxoid changes. To the best of our knowledge, only one case of sarcomatoid salivary duct carcinoma outside a major salivary gland has been reported previously in the literature, and this is the first report of sarcomatoid salivary duct carcinoma arising from the larynx.

Humans↗

PubMed2005

The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy.

PURPOSE: The X-ray repair cross-complementing Group 1 (XRCC1) protein is involved mainly in the base excision repair of the DNA repair process. This study examined the association of 3 polymorphisms (codon 194, 280, and 399) of XRCC1 and lung cancer in terms of whether or not these polymorphisms have an effect on the survival of lung cancer patients who have received radiotherapy. METHODS AND MATERIALS: Between January 2000 and April 2004, 229 lung cancer patients with non-small-cell lung cancer in Stages I-III were enrolled. Genotyping was performed by single base primer extension assay using the SNP-IT Kit with genomic DNA samples from all patients. The haplotype of the XRCC1 polymorphisms was estimated by PHASE version 2.1. RESULTS: The patients consisted of 191 (83.4%) males and 38 (16.6%) females with a median age of 62 (range, 26-88 years). Sixty percent of the patients were included in Stage I-IIIa. The median progression-free and overall survival was 13 months and 16 months, respectively. The XRCC1 codon 194, histology, and stage were shown to be significant predictors of the progression-free survival. The 6 haplotypes among the XRCC1 polymorphisms (194, 280, and 399) were estimated by PHASE v.2.1. The patients with haplotype pairs other than the homozygous TGG haplotype pairs survived significantly longer (p = 0.04). CONCLUSIONS: Polymorphisms of XRCC1 have an effect on the survival of lung cancer patients treated with radiotherapy, and this effect seems to be more significant after the haplotype pairs are considered.

Adult↗