Analysis of the DOK1 gene in breast cancer.

Breast cancer, which is the most common type of cancer among women, is a heterogenous disease. It results from progressive accumulation of genetic and epigenetic alterations in different genes. The Dok1 protein has been identified as the major substrate of protein tyrosine kinases in hematopoietic cells. It is considered as a tumor suppressor due to the reports which describe its inhibitory effect on major oncogenic signaling pathways such as Mek/Erk/PI3k/Akt and Wnt/ß-catenin. In this study, we investigated the mutation frequency of the DOK1 gene in 118 breast tumors using Sanger sequencing and DOK1 mRNA expression level in 63 breast cancer samples using qRT-PCR methods. Although the mutation frequency was low DOK1 mRNA expression levels were significantly reduced (63.5%) in the tumors compared to adjacent non-cancerous tissue. We also correlated expression changes with clinicopathological characteristics. Low mRNA levels correlated with age (p = 0.01) and c-erbB-2 (p = 0.05). In most of the previous reports, down-regulation of DOK1 mRNA expression has been associated with promoter methylation. We identified four different coding sequence alterations in 5.1% (6/118) of the tumor samples. However, all of these alterations were located in the functional domains of the protein. Therefore, these mutations may affect the function and/or cellular localization of the protein and contribute to cancer progression by this way. In conclusion our data indicate that DOK1 acts as a tumor suppressor in breast cancer and association of Dok1 with the c-erbB-2 mediated mechanism of action in breast cancer needs to be investigated.

Downregulation of TCEAL7 expression induces CCND1 expression in non-small cell lung cancer.

Transcription Elongation Factor A-like 7 (TCEAL7) was first reported as a candidate tumor suppressor gene because of its inactivation in ovarian cancer as a result of promoter methylation. Down-regulation of the TCEAL7 gene expression was also associated with other cancers such as endometrial, breast, brain, prostate, gastric cancers, glioblastoma and linked to tumor phenotypes and clinical outcomes. However, there is no report in the literature investigating the role of TCEAL7 in non-small cell lung cancer. Cyclin D1 is an important molecule in the transition from G1 to S phase of the cell cycle, and is frequently deregulated in cancers. Cylin D1 (CCND1) gene is amplified or overexpressed in a variety of tumors. In our previous study we reported that CCND1 over-expression was not associated with amplification in non-small cell lung cancer. Recently, it has been reported that TCEAL7 regulates CCND1 expression through myc-binding E-box sequences. The aim of this study was to investigate the expression of TCEAL7 gene in non-small cell lung cancer and to determine its effect on the CCND1 expression level. For this purpose, expression levels of TCEAL7 and CCND1 genes were investigated in 50 patients with non-small cell lung cancer by quantitative real time polymerase chain reaction (qRT-PCR). TCEAL7 was under-expressed (68%) in non-small cell lung cancer tumor tissues while CCND1 was over-expressed (42%). The TCEAL7 levels negatively correlated with increased CCND1 expression (p = 0.002).

Pediatric Stroke: A Single-Center Experience.

The aim of this study was to evaluate the clinical characteristics, risk factors, treatment, and outcomes of pediatric stroke cases. A total of 118 patients diagnosed with arterial ischemic stroke (AIS), hemorrhagic stroke, and sinovenous thrombosis (SVT) between January 2000 and December 2011 were included. Neonatal cases were excluded. Demographic and clinical findings were retrospectively examined from medical records. We identified 118 patients with stroke. The age of the patients ranged from 1 to 215 months (17.92 y), with a mean age of 5.19±5.25 years. AIS accounted for the majority of cases (n=69, 58.5%), and the major etiology was cardiac disease (17%). Hemorrhagic stroke accounted for 19.5% (n=23) of the cases, and late hemorrhagic disease of the newborn was the major etiology (43%, n=10). SVT accounted for 22% (n=26) of the cases, and the major etiology was otitis media-mastoiditis (27%, n=7). Hemiplegia and headache were the most frequent symptoms for AIS and SVT, respectively. Stroke is rare in children compared with adults; however, it is detected more frequently with better imaging techniques and increased awareness. We found that children with AIS presented more commonly with hemiplegia and children with SVT with headache and strabismus. We did not find an association between thrombophilia and stroke.

ZNF703 is an important player in head and neck cancer.

OBJECTIVES: Despite advances in treatment, head and neck squamous cell carcinoma (HNSCC) remains difficult to treat and the overall survival rate has only modestly improved over the past years. Therefore, there is a need to understand the molecular mechanism of HNSCC. Zinc finger protein 703 (ZNF703) is an oncogenic transcription factor, and ZNF703 gene expression is altered in many cancers as a result of chromosome 8p12 amplification. The purpose of this study was to investigate the expression pattern of ZNF703 in HNSCC in association with CCND1 expression and Akt phosphorylation. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: One hundred and five patients with HNSCC. METHODS: Fifty HNSCC tumour and non-cancerous tissue samples were investigated by qRT-PCR and Western blotting. RESULTS: ZNF703 gene expression was increased in 22.9% of tumour tissues compared with its normal counterparts. The results were correlated with clinicopathological features, copy number variation and survival data. CONCLUSION: ZNF703 over-expression is associated with copy number variation and this over-expression may activate PI3K/Akt signalling pathway in HNSCC.

The investigation of hyaluronic acid and hyaluronidase-1 levels as tumour marker in larynx cancer.

OBJECTIVE: The purpose of this study was to investigate the hyaluronic acid (HA) and hyaluronidase-1 (HYAL-1) levels in laryngeal cancer patients. STUDY DESIGN: Prospective, controlled clinical trial. SETTING: University Medical Center. PARTICIPANTS: Fifty laryngeal squamous cell carcinoma patients and 50 volunteers who gave saliva samples investigated prospectively between 2016 and 2017. METHODS: Hyaluronidase-1 expression was measured by RT-PCR in normal and tumour tissue samples; hyaluronic acid values of saliva and tumour tissues were measured by ELISA method. RESULTS: HYAL-1 expression increased 2.5-fold in tumour tissues compared to normal tissues, and the difference was statistically significant (P < 0.001).Mean saliva HA levels were 103.93 ± 69.04 ng/mL and 177.29 ± 98.44 ng/mL in the patients and controls' saliva specimens, respectively. The difference was not statistically significant (P = 0.657). HA levels were higher in tumour tissue samples than saliva samples, but there was not statistically significant difference between saliva and tumour tissue HA levels. CONCLUSION: HYAL-1 expression in laryngeal squamous cell carcinomas is elevated compared to normal tissues of same patients. Targeting this gene and HA catabolism products may use treatment of larynx cancer in the future.

Investigation of the SLC22A23 gene in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most common cancer of the head and neck. In order to identify differentially expressed genes which may have a role in LSCC carcinogenesis, we performed GeneFishing Assay. One of the differentially expressed genes was the SLC22A23 (solute carrier family 22, member 23) gene. SLC22A23 belongs to a family of organic ion transporters that are responsible for the absorption or excretion of many drugs, xenobiotics and endogenous compounds in a variety of tissues. SLC22A23 is expressed in a various tissues but no substrates or functions have been identified for it. Although the exact function is unknown, single nucleotide polymorphisms (SNPs) which are located in SLC22A23 gene were associated with inflammatory bowel disease (IBD), endometriosis-related infertility and the clearance of antipsychotic drugs. On the other hand SLC22A23 is identified as a prognostic gene to predict the recurrence of triple-negative breast cancer. METHODS: To understand the role of the SLC22A23 gene in laryngeal carcinogenesis, we investigated its mRNA expression level in laryngeal tumor tissue and adjacent non-cancerous tissue samples obtained from 83 patients by quantitative real-time PCR. To understand the association between SNPs in SLC22A23 and LSCC, selected genetic variations (rs4959235, rs6923667, rs9503518) were genotyped. RESULTS: We found that SLC22A23 expression was increased in 46 of 83 tumor tissues (55.4%) and was decreased in 30 of 83 (36.1%) tumor tissues compared to normal tissues. 77.2% of patients were homozygote for genotype rs9503518-AA and they most frequently had histological grade 2 and 3 tumors. We also found that rs9503518-AA genotype is associated with increased SLC22A23 expression. CONCLUSIONS: Our results indicate that SLC22A23 may play a role in the development of laryngeal cancer.

Familial Mediterranean fever in childhood: a single-center experience.

The aim of this study is to present demographic and clinical features, MEFV mutation variations, and treatment response of a large number of pediatric familial Mediterranean fever (FMF) patients from a single tertiary centre. Moreover, we aimed to investigate the current outcome of FMF, namely frequency of amyloidosis in children with FMF. We evaluated 708 FMF patients who were followed up in our clinic and who were under colchicine treatment for at least 6 months. The data were recorded from patient records and also verified by negotiations with patients and parents. The male/female proportion of the cohort was 1.05/1 (n = 362/346). Abdominal pain (89.5%, n = 634) was the most common manifestation of FMF episodes, followed by fever (88.8%, n = 629) and arthritis (40.7%, n = 288). However, arthritis in 23 (8%) of the 288 cases was not self-limited; and they subsequently diagnosed with juvenile idiopathic arthritis in addition to FMF. Homozygote or heterozygote M694V mutation was more frequent in patients with arthritis (63.2%) and chronic arthritis (69.6%) than the whole cohort (53.8%). Erythrocyte sedimentation rate and CRP level were in high levels even during attack-free period in 13.9% (n = 97/697) and 11% (n = 78/670) of the patients, respectively. Proteinuria was found in ten patients (1.4%). Amyloidosis was confirmed by renal biopsy in only two of these cases who were homozygous for M694V and compound heterozygous for M694V/M680I. 47 (6.6%) subjects were considered as colchicine resistant. Homozygote M694V mutation was the most frequent mutation in those resistant cases (63.8%, n = 30), followed by compound heterozygote mutation of M694V/M680I (6.3%, n = 3). Homozygous M694V mutation are still the most frequent mutation and associated with the most severe clinical picture and the worst outcome in Turkish children. M694V genotype seems to be more frequently associated with arthritis as well as with chronic arthritis than other genotypes. Recurrence of FMF episodes as well as amyloidosis could only be managed via strict compliance to colchicine treatment. Frequency of amyloidosis significantly decreased compared to the previous studies. A favorable outcome could be obtained with the anti IL-1 in colchicine-resistant FMF patients.

The EMSY Gene Collaborates with CCND1 in Non-Small Cell Lung Carcinogenesis.

Background: Lung cancer is the leading cause of cancer deaths. The main risk factor is smoking but the risk is also associated with various genetic and epigenetic components in addition to environmental factors. Increases in the gene copy numbers due to chromosomal amplifications constitute a common mechanism for oncogene activation. A gene-dense region on chromosome 11q13 which harbors four core regions that are frequently amplified, has been associated with various types of cancer. The important cell cycle regulatory protein cyclin D1 (CCND1) is an essential driver of the first core region of the Chr11q13 amplicon. Deregulation of CCND1 has been associated with different kinds of human malignancies including lung cancer. The EMSY (c11orf30) gene has been proposed as the possible driver of the fourth core of the 11q13 amplicon and its amplification has been associated with breast and ovarian cancers. There is no report in the literature investigating the EMSY gene in lung cancer. Methods: In this study, expression levels of the EMSY and CCND1 genes were investigated in 85 patients with non small cell lung cancer by Real Time PCR. Results: Expression of the EMSY and CCND1 genes were increased in 56 (65.8%) and 50 (58.8%) of the patients, respectively. Both genes showed a higher expression in the tumors when compared to normal tissues. A strong correlation was present between the expression rates of both genes (p<0.001). Patients with adenocarcinoma had higher expression levels of both genes (p=0.02). Conclusion: We conclude that EMSY and CCND1 work in collaboration and contribute to the pathogenesis of lung cancer.

IL-1ß polymorphism in COPD patients in Turkish population.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterized by persistent airflow limitation and is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Interleukin-1 beta (IL-1ß) is a major pro-inflammatory cytokine expressed by many cells such as macrophages, neutrophils and monocytes and functions in cellular activities such as proliferation, differentiation and apoptosis. Recent studies demonstrate controversial results about the relationship between IL-1ß and COPD. The aim of this study is to investigate the association between IL-1ß -511 (rs 16944) and +3954 (rs 1143634) gene polymorphisms and COPD in Turkish population. MATERIALS AND METHODS: A total of 152 subjects were recruited in the study and divided into three groups: 72 COPD patients, 41 healthy smokers and 39 never-smokers. PCR-RFLP method was used to determine the allele frequencies, genotype and haplotype distributions. RESULT: We did not find any significant difference between the gene polymorphisms and COPD by means of genotype frequencies, haplotype association, stage, gender or smoking status (p< 0.05). CONCLUSIONS: Our results do not show any evidence of association between COPD and IL-1ß -511 and +3954 gene polymorphisms in Turkish population.

Novel mutations and role of the LKB1 gene as a tumor suppressor in renal cell carcinoma.

The tumor suppressor LKB1 gene is a master kinase and inhibits mammalian target of rapamycin (mTOR) by activating AMP-activated protein kinase (AMPK) and AMPK-related kinases. LKB1 is a critical intermediate in the mTOR signaling pathway, and mutations of the LKB1 gene have been implicated in the development of different tumor types. Recent evidence indicates that LKB1 alterations contribute to cancer progression and metastasis by modulating vascular endothelial growth factor (VEGF) production. The Ras homolog enriched in brain (RHEB) protein is a component of the mTOR pathway and functions as a positive regulator of mTOR. However, the mechanisms and effectors of RHEB in mTOR signaling are not well known. In this study, we analyzed the expression of RHEB and HIF1α genes in correlation with LKB1 gene mutations. All coding exons and exon/intron boundaries of the LKB1 gene were analyzed by direct sequencing in 77 renal cell carcinoma (RCC) tumors and 62 matched noncancerous tissue samples. In 51.6 % of the patients, ten different mutations including four novel mutations in the coding sequences and six single nucleotide substitutions in the introns were observed. Rheb and HIF1α expression levels were not statistically different between the tumor and corresponding noncancerous tissue samples. However, expression of the Rheb gene was upregulated in the tumor samples carrying the intron 2 (+24 G→T) alteration. Association between the gene expression and tissue protein levels was also analyzed for HIF1α in a subgroup of patients, and a high correlation was confirmed. Our results indicate that the LKB1 gene is frequently altered in RCC and may play a role in RCC progression.

Mutations and Krüppel-like factor 6 (KLF6) expression levels in breast cancer.

The transcription factor KLF6 gene has been identified as a tumor suppressor because of its inactivation in several types of cancers by different mechanisms. However, there are no data in the literature investigating the KLF6 mutation rate and expression levels in breast cancer. Therefore, the present study was conducted in order to investigate whether genetic alterations of KLF6 in association with the KLF6 mRNA expression levels may play a role in breast carcinogenesis. For this purpose, we analyzed alterations of the KLF6 gene by direct sequencing and the mRNA levels by reverse transcription-PCR (RT-PCR). In addition to four different non-coding alterations, one missense and two silent alterations were identified in the coding sequence. Reduced KLF6 expression was observed in 41 (83.67 %) of the 49 breast cancer tumors. These findings suggest that the mutation profile of the KLF6 gene in breast tumors is similar to other cancer types. However, these mutations do not exert any effect on the gene expression rate. Downregulation of KLF6 during the progression of breast cancer is independent of the mutations and occurs by a different mechanism.

LKB1 mutations and their correlation with LKB1 and Rheb expression in bladder cancer.

Although there are extensive studies on the genetics of bladder cancer, several questions remain unanswered. One of the pathways which are altered in bladder cancer is the mTOR signaling pathway. In the present study, we analyzed the expression of Rheb gene and genetic alterations in the LKB1 gene which are the key components of mTOR pathway. Nine exons of the LKB1 gene were analyzed by direct sequencing in 51 bladder cancer patients. To investigate the expression of Rheb and LKB1, real-time quantitative RT-PCR was performed in bladder tumor and normal bladder tissue samples. We did not observed a statistically significant difference in Rheb or LKB1 expression between the tumor and normal tissue samples. We detected a novel missense mutation creating stop codon in a high percent of the tumor samples. Five different single nucleotide substitutions were also observed in the introns. Our results indicate that LKB1 gene may play a role in the progression of bladder cancer.

Expression of EMSY gene in sporadic ovarian cancer.

The majority of familial breast and ovarian cancers arise from mutations in the BRCA1 and BRCA2 genes. Amplification at the 11q13.5 locus is commonly observed in breast and ovarian cancers. In 2003, Hughes-Davies et al. identified a novel gene (EMSY) at this locus which binds BRCA2 within a region deleted in some cancers. Although little is known about the cellular role of EMSY, indirect evidence suggests that this nuclear protein is capable of silencing the activation potential of BRCA2. In this study we aimed to investigate expression of the EMSY gene and its protein product in sporadic ovarian cancer. Real-time quantitative RT-PCR was performed in 50 ovarian cancer and 17 normal ovarian tissue samples. Overexpression of the EMSY gene was found in 6/50 cases (12%), but in none of the control samples. To determine the EMSY protein by Western blotting, semi-quantitative analysis of the EMSY protein was performed using the Scion Image Gel Analysis Program. Statistical analysis was performed using SPSS 11.5. All patients having EMSY overexpression also displayed increased levels of the EMSY protein. Sporadic ovarian cancer shows overexpression of EMSY at a prevalence similar to that found in breast cancer and the overexpression is correlated with the protein level.

Epigenetic Silencing of SOX15 Is Controlled by miRNAs rather than Methylation in Papillary Thyroid Cancer.

METHODS: In this study, qRT-PCR was used to investigate the expression levels of the SOX15 gene and of miR-182, miR-183, miR-375, and miR-96 in thyroid tumors and adjacent noncancerous tissues. We also investigated the methylation status of the SOX15 promoter by methylation-specific PCR in tumors and adjacent noncancerous tissues. RESULTS: We observed a statistically significant downregulation of SOX15 expression in tumors compared to noncancerous tissue samples. The methylation levels of tumors and matched noncancerous tissues were similar, but miR-182, miR-183, and miR-375 expression levels were elevated in tumor tissues compared to noncancerous tissue samples. CONCLUSIONS: Our results indicate that SOX15 gene expression is associated with the pathogenesis of papillary thyroid carcinoma (PTC), and the epigenetic control of the SOX15 gene is regulated by miRNAs rather than by promoter methylation.

No Tumor Suppressor Role for LKB1 in Prostate Cancer.

To elucidate the pathogenesis of prostate diseases, following in silico analysis, the LKB1 gene was selected for further investigation. The LKB1 gene has been associated with poor prognosis and is frequently mutated in different types of cancers. In this study, 50 benign prostatic hyperplasia (BPH) and 57 prostate cancer (PCa) tissues, including matched normal tissue for the patients, were analyzed by qRT-PCR and DNA sequencing for LKB1 expression and the mutation profile, respectively. Expression of LKB1 was increased in 60.7% of the PCa tissues compared with noncancerous tissue samples (p ≤ 0.001). However, LKB1 expression was lower when compared with normal tissues in BPH (p = 0.920). Four coding sequence alterations were detected in BPH. Three silent mutations were located in codons 9, 32, and 275 and a missense mutation was observed in codon 384. Six alterations were identified in the intronic regions of the LKB1 gene in both PCa and BPH. Five mutations were observed in both patient groups. A new alteration in intron 6 was observed in a patient with PCa. The LKB1 gene may be associated with benign transformations rather than the tumors in prostate pathogenesis when its expression and mutation status are considered. However, the mechanism of LKB1 in PCa needs further studies.

WWOX gene may contribute to progression of non-small-cell lung cancer (NSCLC).

Lung cancer is the most common cause of cancer-related death worldwide and, like many other cancers, is affected by different genetic, epigenetic, and environmental factors. The WW domain-containing oxidoreductase (WWOX) gene is a tumor-suppressor gene located on chromosome 16q23.3-24.1, and it has been shown that it loses its function due to alterations in genetic and epigenetic mechanisms. The aim of this study is to investigate the relationship between lung cancer and WWOX gene. Tumor tissue samples, corresponding normal tissues, and blood samples obtained from 50 lung cancer patients were involved in the study. We analyzed methylation profile by methylation-specific PCR and mutations and polymorphisms by DNA sequencing. Methylation analysis showed that promoter hypermethylation was present in 38 of 50 (76%) patients. In addition, promoter region of WWOX gene of younger patients was more frequently methylated than older patients. Using DNA sequencing, we found four genetic alterations in WWOX gene. Two of them were germline mutations (Exon 4 and 7), and two of them were polymorphic (Exon 6 and 8). We found a new mutation in exon 7 (Arg-254-->Cys) which has not been described previously. The changes in the short-chain dehydrogenase domain of the protein caused by the genetic alterations may affect the function of the gene. We conclude that hypermethylation of WWOX gene promoter region and mutations in the gene might be related to lung carcinogenesis.

Investigation of glutathione S-transferase M1 and T1 deletions in lung cancer.

Glutathione S-transferases (GSTs) M1 and T1 are known to be polymorphic in humans. Both polymorphisms are due to gene deletions which are responsible for the existence of null genotypes. Previous studies have suggested that GST genotypes may play a role in determining susceptibility to a number of unrelated cancers, including lung cancer. The GSTM1 and GSTT1 polymorphisms were determined by PCR-based analysis in 75 lung cancer patients and 55 controls. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. The frequencies of GSTM1 and GSTT1 null genotypes were 37.3 and 22.7% in lung cancer patients and 27.3 and 16.4% in controls, respectively. When analyzed by histology the GSTM1 null genotype was more prevalent in squamous-cell carcinoma and adenocarcinoma patients. Whereas, GSTT1 null genotype frequency was lower in small-cell lung cancer patients than controls. But these differences were not statistically significant. According to smoking status, null genotype for both gene are associated with an increase in risk for lung cancer. Our results suggest that GSTM1 and GSTT1 polymorphisms may play a role in the development of lung cancer for some histological subtypes and modifies the risk of smoking-related lung cancer.

Silencing of Wwox Increases Nuclear Import of Dvl proteins in Head and Neck Cancer.

Background: Wnt signaling pathway is associated with a variety of human cancers, including HNSCC. Wnt proteins control cellular events such as proliferation, fate specification, polarity, and migration by transducing signals to the nucleus through several cytoplasmic relay proteins. Although activation of the Wnt/ß-catenin pathway is a frequent event in various cancers, there is limited knowledge on the contribution of this signaling mechanism in HNSCC. The Wwox tumor suppressor protein participates in the regulation of Wnt signaling by interacting with Dvl proteins. Methods: In this study, we used qRT-PCR and western blotting to examine the mRNA and protein levels of the Dvls in association with WWOX in HNSCC cell lines and tumor tissues. Results: We found that silencing of WWOX leads to increased nuclear localization of the Dvl proteins in cell lines. However, we detected an increase only in the nuclear localization of Dvl-1 in tumor tissues. Conclusions: Our results suggest that aberrant WWOX expression contributes to HNSCC through the Wnt signaling pathway. Decreased expression of WWOX may function in HNSCC progression by allowing the nuclear localization of Dvl proteins.

Methylation profiles in breast cancer.

In this study, we sought to assess the aberrant methylation of multiple tumor-suppressor genes in a single reaction by using methylation-specific multiplex ligation-dependent probe amplification. Breast tumors and corresponding normal tissues of 77 patients were analyzed. In this study, 17 of 24 genes displayed promoter methylation in one or more of the tumor samples. The most frequently methylated genes were RASSF1 and GSTP1, followed by DAPK1 and CDKN2B. Our data indicate that the methylation of specific genes is a frequent event in breast cancer and show that MS-MLPA is a powerful tool to analyze epigenetic alterations for diagnostic, as well as therapeutic, purposes.

p53 codon 72 polymorphism and HPV status in lung cancer.

BACKGROUND: Several risk factors, both environmental and genetic, have been associated with the pathogenesis of lung cancer. A common polymorphism at codon 72 of exon 4 of the p53 gene encoding either an arginine or proline has been shown to confer susceptibility to the development of different human malignancies. This polymorphism affects proteolytic degradation of p53 promoted by the HPV-E6 protein and represents a risk factor for human-papillomavirus-induced carcinogenesis. MATERIAL/METHODS: A total of 65 patients with lung cancer were recruited into the study and 87 healthy subjects were used as the control group. The codon 72 polymorphism was determined by the PCR-RFLP method. Presence of human papillomavirus DNA was analyzed by polymerase chain reaction using MY09 and MY11 consensus primers and hybridization with HPV16 and HPV18 specific probes. RESULTS: The frequencies of the Arg and Pro alleles were 68.46% and 31.54% in lung cancer patients and 55.7% and 44.3% in the healthy control subjects, respectively. These differences were statistically significant. Human papillomavirus DNA was detected in the blood circulation of only 1 patient. CONCLUSIONS: Our results suggest that the Arg/Arg genotype may represent a potential risk factor for the development of lung cancer independent of the HPV infection.