STRA6 Polymorphisms Are Associated With EGFR Mutations in Locally-Advanced and Metastatic Non-Small Cell Lung Cancer Patients (original) (raw)
Related papers
Biomolecules
Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian population. A total of 129 patients with primary lung cancer and 129 matched healthy controls were recruited into this study. EGFR rs712829, rs712830, rs2072454, and rs11543848 single nucleotide polymorphisms (SNPs) were genotyped to test for their association with lung cancer risk. A significant association was observed between the rs712829 SNP and lung cancer risk (p < 0.05) where the GG + GT genotypes were higher in lung cancer patients when compared to controls. In addition, no association was detected between rs712830, rs2072454, and rs11543848 SNPs and lung cancer risk. When patients were stratified according to the lung cancer type, a significant association was detected between both rs712829 and r...
Expression of Retinoid Receptor Genes and Proteins in Non-Small-Cell Lung Cancer
JNCI Journal of the National Cancer Institute, 1999
Background: Retinoids can suppress carcinogenesis in high-risk nonneoplastic bronchial lesions and can reduce the risk of second primary nonsmall-cell lung cancer (NSCLC). The effects of retinoids are mediated by nuclear receptors, i.e., the retinoic acid receptors (RAR␣, RAR, and RAR␥) and the retinoid X receptors (RXR␣, RXR, and RXR␥). We investigated whether abnormalities in the in vivo expression of retinoid receptors are observed in NSCLC. Methods: Expression of retinoid receptors in paired specimens of normal and cancerous tissues from the lungs of 76 patients with NSCLC was studied by use of antiretinoid receptor antibodies (except those against RXR␥) and immunohistochemistry. RAR messenger RNAs were analyzed by use of in situ hybridization and by reverse transcriptionpolymerase chain reaction (RT-PCR). Samples were also studied for loss of heterozygosity (LOH) at chromosome 3p24. All P values are two-sided. Results: All studied receptors were expressed in normal lung cells and in high-risk non-neoplastic lesions. In tumor cells, overexpression of RXR␣ and RAR␣ was frequently observed. In contrast, RXR expression decreased in 18% of the tumor specimens. Furthermore, there was a marked decrease in the expression of RAR in 63% of the tumors (P<.0001). Decreased expression of RAR␥ was observed by RT-PCR in 41% of the tumors (P<.0001). LOH at 3p24 was observed in 41% of the tumor specimens from informative patients and in 20% of the non-neoplastic lesions. Conclusions: Expression of RAR␣ and RXR␣ is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RAR, RAR␥, and RXR as well as a high frequency of LOH at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered retinoid receptor expression may play a role in lung carcinogenesis. [J Natl Cancer Inst 1999;91:1059-66]
The EGFR rs2233947 polymorphism is associated with lung cancer risk: a study from Jordan
Acta Biochimica Polonica, 2019
The epidermal growth factor receptor (EGFR) is a tyrosine kinase cell surface protein that plays a role in the process of carcinogenesis. In this study, we investigated the association between EGFR rs2233947 and rs884225 SNPs and the risk of lung cancer. A total of 258 participants (129 lung cancer patients and 129 healthy controls) took part in the study. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used to genotype EGFR SNPs. A strong association was detected between rs2233947 and lung cancer (P<0.01). Compared with the rs2293347 GG genotype, the AA/AG genotypes were associated with a significantly decreased risk of lung cancer (adjusted OR = 0.28, 95% confidence interval [CI]=0.13–0.61, P<0.01). EGFR rs2233947 correlated with lung cancer in males, smokers, and in the squamous cell carcinoma lung cancer subtype (P<0.01). Haplotype analysis of rs2233947 and rs884225 showed that the AA haplotype was associated with a significan...
Tumor Biology, 2016
The purpose of this study was to determine the frequencies of EGFR −216G>T, −191C>A, and 181946C>T in Serbian non-small cell lung cancer (NSCLC) patients, as well as to compare it with healthy individuals, in order to assess their potential importance for lung cancer in Serbia. The study involved 56 NSCLC patients and 53 unrelated healthy volunteers, and genotyping was performed on DNA samples obtained from formalin-fixed paraffin-embedded lung tumor tissue and blood, respectively. This was the first time to show genotype frequencies of those single nucleotide polymorphisms for this study group from the territory of the Republic of Serbia. There was very strong evidence of association between age and death due to lung cancer (Pearson chi-square = 43.439, df = 2, p < 0,001), as well as between ever smoking and death due to lung cancer (Pearson chisquare = 31.727, df = 1, p < 0.001). When dominant genetic model (GG vs. GT+TT) was used for −216G>T, we have found significant association (p = 0.012) between −216GG genotype and NSCLC patients within smokers' subgroup. So, carriers of −216GG genotype had higher risk (OR = 4.33, 95 % CI = 1.324-14.179) than noncarriers (GT and TT) for developing non-small cell lung cancer in our patients.
Serum retinol and retinol-binding protein levels do not predict subsequent lung cancer
American journal of epidemiology, 1986
Retinol and retinol-binding protein levels were measured in sera previously obtained, and stored in the frozen state, at multiphasic health checkups from 151 persons subsequently found to have lung cancer (cases) and 302 persons who remained free of cancer (controls). Two controls were matched to each case for sex, skin color, age, date of multiphasic health checkup, and aspects of the smoking habit. Mean levels in cases and controls were, respectively, retinol: 82.17 and 82.37 micrograms/dl (p = 0.93), and retinol-binding protein: 6.04 and 6.00 mg/dl (p = 0.81). Mean differences between cases and controls were, retinol: 0.195 micrograms/dl with 95% confidence limits, -3.91 and 4.30 micrograms/dl; retinol-binding protein: -0.033 mg/dl with 95% confidence limits, -0.31 and 0.24 mg/dl. No significant trend in relative risk of lung cancer was observed when the retinol or retinol-binding protein distribution was divided into quintiles. No significant associations were observed in subgro...
Germline Polymorphisms in EGFR and Survival in Patients With Lung Cancer Receiving Gefitinib
Clinical Pharmacology & Therapeutics, 2007
The purpose of this study was to evaluate associations between germline epidermal growth factor receptor (EGFR) variants involved in transcriptional regulation and overall survival in white patients with non-small-cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor, gefitinib. Of 175 consecutive patients treated with oral gefitinib (250 mg/day), 170 (median age: 67 years; 72% men) were evaluable for genotyping and survival. Fifty-five patients (33%) had stable disease and 17 (10%) had an objective response. The most common of four haplotypes was G-C (EGFR*1) at the EGFR À216G4T and À191C4A loci (frequency, 0.45). After adjusting for performance status, previous platinum-containing chemotherapy and occurrence of skin rash or diarrhea during the first treatment cycle in patients with performance status 0 or 1 (N ¼ 139), the absence of EGFR*1 was associated with significantly better survival (hazard ratio: 0.54; 95% confidence interval: 0.32-0.91; P ¼ 0.015). The results may help identify patients with NSCLC who can benefit from gefitinib treatment.
BMC Cancer, 2007
Background Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population. Methods We first examined the frequencies of 39 candidate polymorphisms in the EGFR gene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C>T, 142285G>A, 162093G>A, 181946C>T and 187114T>C) that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls. Results Of the 5 polymorphisms, the 181946C>T genotype distribution was significantly different between the cases and controls (P = 0.04). Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45–0.88, P = 0.007)....
International Journal of Molecular Sciences
For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotyp...