Comparison of the KRAS/EGFR mutation profile and survival of “collegiate smokers” and never smokers with advanced lung cancers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7580-7580
Author(s):  
Anna M. Varghese ◽  
Camelia S. Sima ◽  
Jamie E. Chaft ◽  
Melissa Lynne Johnson ◽  
Yelena Yuriy Janjigian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Biology ◽  
Egfr Mutation ◽  
Stage Iiib ◽  
Smoking History ◽  
Egfr Mutations ◽  
Lung Cancers ◽  
Mutation Profile ◽  
Former Smokers ◽  
Never Smokers

7580 Background: In practice, we encounter patients (pts) with lung cancers who state they smoked only while in college. The impact of this degree of tobacco use on cancer biology is unknown. We have shown that EGFR mutations are less common in pts who smoked > 15 pack years (PY). We hypothesize that among pts with lung cancer the KRAS / EGFR mutation profile and overall survival (OS) of “collegiate smokers” (former smokers who smoked between 101 lifetime cigarettes and 5 PY) will be distinct from never smokers and former smokers with ≥ 15 PY. Methods: We collected age, sex, stage, and survival for pts evaluated from 2004 - 2009 with stage IIIB/IV lung cancer with known KRAS and EGFR status. ALK testing was not available routinely during this time. Smoking history was obtained using a patient completed survey. The Fisher exact test was used to compare mutation profiles. The log rank test was used to compare OS. Results: Smoking history and clinical data were available for 852 pts with Stage IIIB/IV lung cancer with known KRAS and EGFR status: 307 never smokers, 178 current smokers, and 367 former smokers. Of the former smokers, 55 were “collegiate smokers”, 61 had smoked 5-15 PY, and 251 had smoked ≥ 15 PY. The KRAS / EGFR mutation profiles by smoking history are shown below (Table). The KRAS / EGFR mutation profile of “collegiate smokers” is distinct from those of pts who were never smokers (p < .001) and former smokers with ≥ 15 PY (p < .001) but similar to that of pts who were former smokers with 5-15 PY (p = 0.9). Median OS after diagnosis of stage IIIB/IV lung cancer for “collegiate smokers” was 25 months (mos), compared to 32 mos for never smokers (p = 0.4) and 21 mos for former smokers with ≥ 15 PY (p = 0.63). Conclusions: “Collegiate smokers” are a distinct group of pts with a higher incidence of KRAS mutations and lower incidence of EGFR mutations compared to never smokers. These data suggest that even a small amount of cigarette smoking influences the biology of lung cancer. These findings reinforce the importance of doing mutation testing routinely for all pts with lung cancer to guide clinical care. [Table: see text]

Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas

2006 ◽  
Vol 24 (11) ◽  
pp. 1700-1704 ◽  
Author(s):  
DuyKhanh Pham ◽  
Mark G. Kris ◽  
Gregory J. Riely ◽  
Inderpal S. Sarkaria ◽  
Tiffani McDonough ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Egfr Mutations ◽  
Epidermal Growth ◽  
Former Smokers ◽  
Never Smokers ◽  
Lung Adenocarcinomas ◽  
Exon 19

Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit < 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

EGFR mutation analysis from REASON: A registry for the epidemiologic and scientific evaluation of EGFR mutation status in newly diagnosed NSCLC patients stage IIIB/IV.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18016-e18016 ◽  
Author(s):  
Wolfgang Schuette ◽  
Wilfried Ernst Erich Eberhardt ◽  
J.-Mathias Graf von der Schulenburg ◽  
Manfred Dietel ◽  
Peter Schirmacher ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Smoking Status ◽  
Epidemiological Data ◽  
Standard Test ◽  
Test Method ◽  
Stage Iiib ◽  
Egfr Mutations ◽  
Newly Diagnosed ◽  
Never Smokers ◽  
Nsclc Patients

e18016^ Background: Somatic mutations in the EGFR gene predict for sensitivity to EGFR TKI in patients with adv. NSCLC, yet limited data exists on EGFR mutation rates of all 4 exons in all NSCLC histologies. Methods: The REASON study (NCT00997230) aims to generate data on EGFR mutation (M) status, association of EGFR-M status with clinico-pathological parameters, treatment decisions and clinical outcomes for EGFR M+ patients from a large sample of stage IIIB/IV NSCLC patients in Germany. 4279 subjects for whom EGFR M testing was planned were enrolled at 151 sites (85% hospital based) in Germany. Standard test method was Sanger sequencing. While analysis of exons 19 and 21 was obligatory, exons 18 and 20 were not routinely done at all labs. Primary objectives are epidemiological data on EGFR M status and correlation with clinico-pathological features. Secondary aims are clinical outcome of all EGFR M+ patients (PFS, OS, DCR), clinical management and pharmaco-economic data associated with diagnosis and treatment of EGFR M+ patients. Results: A 2nd interim analysis provided baseline data on 3973 patients. 63% were male; 82% ever-smokers, 18% never-smokers. Adenocarcinoma is most frequent (69%), followed by squamous epithelial carcinoma (19%). 379 patients had EGFR mutations (9.9%) with 9.5% predicting TKI sensitivity and 0.4% resistance. Most common were exon 19 deletions (50%; with 35% DelE746-A750) followed by exon 21 mutations (36.8%; with 72% L858R). Multivariate analysis revealed association of gender, smoking status and histological subtype with EGFR M status (Table). 50% of M+ patients received 1st line TKI vs. 48% doublet CTX. Conclusions: REASON provides the largest data base yet on EGFR M status in Caucasian patients with newly diagnosed stage IIIB/IV NSCLC. Smoking followed by adeno-carcinoma was the strongest predictive factor for EGFR M. Only 50% of EGFR M+ patients received 1st line TKI. [Table: see text]

Assessment of feasibility and willingness of former heavy smokers to participate in chemoprevention trials to prevent lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21155-e21155
Author(s):  
Nagi B. Kumar ◽  
Gwendolyn P. Quinn ◽  
Theresa Crocker ◽  
Mark Alexandrow ◽  
Jhanelle Elaine Gray ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Smoking History ◽  
Cancer Center ◽  
X Rays ◽  
Lung Cancers ◽  
Multiple Blood ◽  
Former Smokers ◽  
Heavy Smokers

e21155 Background: Over 50% of new lung cancers occur in former smokers, who often are seeking strategies to reduce their lung cancer risk. However, recruitment and retention of participants in chemoprevention trials continues to be costly and presents unique challenges. Evaluation of feasibility and knowledge of challenges are critical to inform design and ensure accrual in chemoprevention trials.The study assessed interest and willingness of former heavy smokers to participate in a chemoprevention clinical trial using a botanical agent to prevent lung cancer. Methods: An introductory letter and survey instrument that included the goal of the survey, epidemiological and smoking history, acceptability of trial procedures, perception of lung cancer risk and interest in participating in this trial were mailed to 500 consecutive, former heavy smokers with no cancer from a database of 826 subjects at the Moffitt Cancer Center. Results: 202 (40.4%) men and women returned completed surveys. 98% of respondents were over age 60 and 56% had an undergraduate education or higher. The average years smoked was 40.7 (SD 11.9) pack years. 76% believed there was a 50% chance or greater of developing lung cancer. In response to interest and motivation to participate, 92-96% reported interest in receiving free lung exams, health status monitoring and knowing their lung cancer risk. 88% were interested in being a part of a trial to evaluate a botanical agent for lung cancer prevention. Over 92% of subjects reported a willingness to comply with study requirements, multiple blood draws and trips to the Center, spiral CTs and chest x-rays. Subjects were relatively less enthusiastic (73-79%) about undergoing bronchoscopy, taking multiple study agents and possible assignment to a placebo arm. Conclusions: Our study strongly suggests feasibility, highlights potential challenges and the significant interest and willingness of former smokers to participate in chemoprevention trials.

Clinicopathologic features of EML4-ALK mutant lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11021-11021 ◽  
Author(s):  
A. T. Shaw ◽  
D. Costa ◽  
M. Mino-Kenudson ◽  
S. Digumarthy ◽  
B. Y. Yeap ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Direct Sequencing ◽  
Smoking History ◽  
Similar Response ◽  
Clinicopathologic Features ◽  
Platinum Based Chemotherapy ◽  
Never Smokers ◽  
Egfr Mutant ◽  
Egfr Tkis

11021 Background: EML4-ALK is a novel fusion oncogene in non-small cell lung cancer (NSCLC). The fusion results from a small inversion within chromosome 2p, leading to expression of a constitutively activated, chimeric tyrosine kinase. The clinicopathologic features of these patients have not been definitively established. Furthermore, the clinical outcome of these patients is unknown. Here we present the largest series of EML4-ALK mutants to date, and the first analysis of treatment response and survival in metastatic patients with and without EML4-ALK. Methods: Patients with NSCLC were selected for genetic screening based on 2 or more of the following characteristics: female gender, Asian ethnicity, never or light smoking history, and adenocarcinoma histology. The EML4-ALK inversion was identified using FISH and confirmed by IHC for ALK expression. EGFR mutation status was determined by direct sequencing of EGFR exons 18–21. Results: Of 141 patients screened, 18 (13%) were ALK mutant, 31 (22%) were EGFR mutant, and 92 (65%) were wild-type (WT) for both ALK and EGFR. The majority of tumors were adenocarcinomas, with ALK but not EGFR mutant tumors strongly associated with the signet ring cell subtype. Compared to the EGFR mutant and WT cohorts, patients with ALK mutant tumors were significantly younger (median age 52.5 vs 64 yrs, p=0.003), and more likely to be male (61% vs 30%, p=0.015). ALK mutants, like EGFR mutants, were also more likely to be light/never smokers compared with WT patients (100% vs 43%, p<0.001). Among patients with metastatic disease, there was a significant association between EML4-ALK and resistance to EGFR TKIs, with no responses by RECIST in the ALK cohort. ALK mutants and WT patients showed similar response rates to platinum-based chemotherapy (60% vs 65%, p=1), and had similar 1-yr survival rates (81% vs. 66%, p=0.43). Conclusions: EML4-ALK defines a new molecular subset of NSCLC with distinct clinical and pathologic characteristics. The frequency of EML4-ALK is particularly high in light/never smokers without EGFR mutation. These patients do not benefit from EGFR TKIs and should be treated with other standard agents or ALK targeted therapies. [Table: see text]

Small cell lung cancer (SCLC) among patients who are never smokers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7593-7593
Author(s):  
Anna M. Varghese ◽  
Helena Alexandra Yu ◽  
Helen H. Won ◽  
Camelia S. Sima ◽  
Gregory J. Riely ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Egfr Mutation ◽  
De Novo ◽  
Egfr Mutations ◽  
Kras Mutations ◽  
Lung Cancers ◽  
Never Smokers ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Generation Sequencing

7593 Background: Although most patients (pts) with SCLC are current or former smokers, SCLC has been reported in pts who are never smokers, most recently in pts with EGFR-mutant lung cancers who develop acquired resistance (AR) to EGFR tyrosine kinase inhibitors (TKIs). We describe clinical, pathologic, and molecular characteristics of never-smoking pts with SCLC at diagnosis and in the AR setting. Methods: We identified cases through systematic review of pts seen at MSKCC from 2005 – 2012. Smoking history was obtained prospectively. SCLC diagnosis was confirmed by expert pathology review. We collected age, sex, stage, treatment, and survival data. EGFR, KRAS, PIK3CA, and ALK testing and next generation sequencing of 279 cancer genes was performed on available samples. Results: 2.2% (23/1040, 95% CI 1.5 to 3.3%) of pts with SCLC seen at MSKCC were never smokers: 61% women, median 64 years, 74% extensive stage, and 22% with brain metastases at diagnosis. 83% (19/23) had de novo SCLC, whereas only 17% had SCLC as AR to EGFR TKI after treatment for EGFR-mutant lung cancers, all of whom had persistent EGFR mutation confirmed at resistance. Median survival from SCLC diagnosis is 23 months (95%CI: 11-26) for all pts and 23 months (95% CI: 8–27) for the 19 pts with de novo SCLC. Pathologic review demonstrated 19 cases of pure SCLC and 4 mixed histology cases with SCLC and other histologies. Treatment history was available for 15/19 pts with de novo SCLC: 53% etoposide-platinum sensitive. ALK rearrangement and KRAS mutations were identified in 0/5 and 0/10, respectively. One pt with de novo mixed SCLC and adenocarcinoma had an EGFR mutation and another pt with de novo pure SCLC had EGFR and PIK3CA mutations. Mutations were identified in p53 and Rb1 with amplification in TERT in 1 sample to date tested with next generation sequencing. Conclusions: 2% of pts with SCLC are never smokers. While transformation to SCLC can occur in the setting of AR to EGFR TKI, de novo SCLC occurs in the majority of our never smokers with this disease. EGFR mutations uniformly exist in SCLC in the AR setting. EGFR mutations were rare, and we found no KRAS mutations or ALK rearrangements. Comprehensive, multiplexed genotyping can aid in providing optimal care and facilitate research in this unique population.

scholarly journals The Role of Mutation Status of the Epidermal Growth Factor Receptor Gene In Advanced Non–Small Cell Lung Cancer

Medicina ◽  
2012 ◽  
Vol 48 (4) ◽  
pp. 25 ◽  
Author(s):  
Neringa Vagulienė ◽  
Marius Žemaitis ◽  
Valdas Šarauskas ◽  
Astra Vitkauskienė ◽  
Skaidrius Miliauskas
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Positive Group ◽  
Epidermal Growth ◽  
Never Smokers

Objective. The aim of this study was to examine the prevalence of epidermal growth factor receptor (EGFR) gene mutations among patients with advanced nonsquamous non–small cell lung cancer (NSCLC) treated in our institution and to evaluate the associations between EGFR mutations and clinicopathological characteristics. Materials and Methods. A total of 103 patients with NSCLC were examined from April 2010 to September 2011. The patients were screened for EGFR mutations in exons 19 and 21 using sequence analysis. Results. EGFR mutations were detected in 10 patients (9.71%): 23.1% of women and 5.2% of men (P<0.05), 31.8% of never-smokers and 4.7% of smokers (P<0.05), and 12.3% of patients with adenocarcinomas and 6.25% of patients with large cell carcinomas (P>0.05). Eight mutations (80.0%) were found in exon 21: 7 patients had the L858R mutation and 1 patient had the L861G mutation. Two mutations (20.0%) were found in exon 19: 1 patient had the L747-A748 deletion and 1 patient had the L747-A750insE deletion. The overall response rate was significantly greater in the EGFR mutation-positive group than in the EGFR mutation-negative or control groups (P<0.05). The median progression-free survival in the EGFR mutation-negative group and the control group that received systemic standard chemotherapy was 5.6 months (95% CI, 4.3 to 7.0) and 5.3 months (95% CI, 4.9 to 5.7), respectively, but it was not achieved in the EGFR mutation-positive group that received EGFR tyrosine kinase inhibitors (P<0.05). Conclusions. The frequency of EGFR mutations in our patients with nonsquamous NSCLC was found to be similar to that reported in Europe. EGFR mutations were more frequent in women and never-smokers

scholarly journals Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations

2011 ◽  
Vol 29 (15) ◽  
pp. 2046-2051 ◽  
Author(s):  
Paul K. Paik ◽  
Maria E. Arcila ◽  
Michael Fara ◽  
Camelia S. Sima ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Clinical Characteristics ◽  
Median Overall Survival ◽  
Smoking History ◽  
Egfr Mutations ◽  
Braf Mutations ◽  
Former Smokers ◽  
Lung Adenocarcinomas

Purpose BRAF mutations occur in non–small-cell lung cancer. Therapies targeting BRAF mutant tumors have recently been identified. We undertook this study to determine the clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. Patients and Methods We reviewed data from consecutive patients with lung adenocarcinoma whose tumors underwent BRAF, EGFR, and KRAS mutation testing as well as fluorescence in situ hybridization for ALK rearrangements. Patient characteristics including age, sex, race, performance status, smoking history, stage, treatment history, and overall survival were collected. Results Among 697 patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%; 95% CI, 2% to 4%). The BRAF mutations identified were V600E (50%), G469A (39%), and D594G (11%). Mutations in EGFR were present in 24%, KRAS in 25%, and ALK translocations in 6%. In contrast to patients with EGFR mutations and ALK rearrangements who were mostly never smokers, all patients with BRAF mutations were current or former smokers (P < .001). The median overall survival of advanced-stage patients with BRAF mutations was not reached. In comparison, the median overall survival of patients with EGFR mutations was 37 months (P = .73), with KRAS mutations was 18 months (P = .12), and with ALK rearrangements was not reached (P = .64). Conclusion BRAF mutations occur in 3% of patients with lung adenocarcinoma and occur more commonly in current and former smokers. The incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in melanoma.

Influence of smoking dose on the outcome of Japanse patients with non-small cell lung cancer who had gefitinib treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19004-e19004
Author(s):  
K. Asami ◽  
M. Kawahara ◽  
S. Atagi ◽  
T. Kawaguchi ◽  
A. Kubo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Egfr Mutation ◽  
Small Cell ◽  
Smoking History ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Heavy Smokers

e19004 Background: Non-smoking history and epidermal growth factor receptor (EGFR) mutation are associated with increased sensitivity to gefitinib in non-small cell lung cancer (NSCLC). However, it is still unclear how much smoking dose is associated with survival and response to gefitinib among smokers. Methods: NSCLC patients (pts) with detailed smoking history who received gefitinib at our institution between 9/02 and 9/04 were reviewed. An analysis was conducted to the pts for association between smoking dose, EGFR mutations, performance status (PS), response and overall survival using multivariate analysis. Results: Data were available for 100 pts including 30 females and 70males. We expressed smoking dose as pack year (Py).The median dose of smoking was 32 Py (0.1–100 Py). We defined the group of <10 Py as light smokers(17 pts) and the other group of 10 Py or more as heavy smokers(83 pts). We detected 31(31%) EGFR mutation (median 14 Py 0.1–75 Py) with exon 18 / 19 /21 mutation;3/17/11 pts .Cox survival analysis showed that overall survival was preferably associated with small dose of smoking(<10 Py)(HR=0.505; [95% CI 0.277–0.921; P=0.013]), EGFR mutation(HR=0.452[95% CI 0.235–0.87;P=0.035])and PS;0–1(HR=0.347 [95% CI 0.207–0.583 P<0.001]). EGFR mutations were significantly more frequently observed in light (12/17:71%) than heavy smokers(19/83:23%) (p<0.001). Disease control rate(DCR) was significantly higher in light (13/17;76%;PR 6, SD 7) than heavy smokers(29/83;35%;PR 15, SD 14)(P=0.002), but there was not significant difference between those groups in terms of response rate (RR)(P=0.187). There were significant differences between pts with EGFR mutations (PR 13 SD 14; RR 42%,DCR 87%) and pts without EGFR mutations (PR 8 SD 15; RR 12%, DCR 33%) in terms of RR(P<0.001) and DCR(P<0.001). In pts with EGFR mutation, there was no significant difference between light and heavy smokers in terms of RR (light smokers 5/10, heavy smokers 8/21; P=0.701) and DCR (light smokers 10/10, heavy smokers17/21; P= 0.277). Conclusions: EGFR mutations were predictive factor and prognostic factor. Small dose of smoking (< 10 Py) was prognostic factor, however it was not a predictive factor of smokers with NSCLC. No significant financial relationships to disclose.

Lung Cancer Risk Reduction After Smoking Cessation: Observations From a Prospective Cohort of Women

2003 ◽  
Vol 21 (5) ◽  
pp. 921-926 ◽  
Author(s):  
J.O. Ebbert ◽  
P. Yang ◽  
C.M. Vachon ◽  
R.A. Vierkant ◽  
J.R. Cerhan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Smoking Cessation ◽  
Cancer Risk ◽  
Risk Reduction ◽  
Prospective Cohort ◽  
Lung Cancer Risk ◽  
Smoking History ◽  
Cox Regression Analysis ◽  
Former Smokers ◽  
Never Smokers

Purpose: We conducted this study because the duration of excess lung cancer risk among former smokers has been inconsistently reported, doubt has been raised regarding the population impact of smoking cessation, and differential risk reduction by histologic cell type after smoking cessation needs to be confirmed. Methods: The Iowa Women’s Health Study is a prospective cohort study of 41,836 Iowa women aged 55 to 69 years. In 1986, mailed questionnaires were used to collect detailed smoking history. Age-adjusted lung cancer incidence through 1999 was analyzed according to years of smoking abstinence. Relative risks were estimated using Cox regression analysis. Results: There were 37,078 women in the analytic cohort. Compared with the never smokers, former smokers had an elevated lung cancer risk (relative risk, 6.6; 95% confidence interval, 5.0 to 8.7) up to 30 years after smoking cessation for all former smokers. However, a beneficial effect of smoking cessation was observed among recent and distant former smokers. The risk of adenocarcinoma remained elevated up to 30 years for both former heavier and former lighter smokers. Conclusion: The risk for lung cancer is increased for both current and former smokers compared with never smokers and declines for former smokers with increasing duration of abstinence. The decline in excess lung cancer risk among former smokers is prolonged compared with other studies, especially for adenocarcinoma and for heavy smokers, suggesting that more emphasis should be placed on smoking prevention and lung cancer chemoprevention.

scholarly journals Potential Impacts of Interleukin-17A Promoter Polymorphisms on the EGFR Mutation Status and Progression of Non-Small Cell Lung Cancer in Taiwan

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 427
Author(s):  
Kai-Ling Lee ◽  
Tsung-Ching Lai ◽  
Yao-Chen Wang ◽  
Pei-Chun Shih ◽  
Yi-Chieh Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Smoking History ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Promoter Polymorphisms ◽  
Mutation Status

Non-small cell lung cancer (NSCLC) is a typical inflammation-associated cancer, and lung adenocarcinoma (LUAD) is the most common histopathological subtype. Epidermal growth factor receptor (EGFR) mutations are the most common driver mutations of LUAD, and they have been identified as important therapeutic targets by EGFR tyrosine kinase inhibitors. Interleukin (IL)-17A secreted by T-helper 17 lymphocytes is a proinflammatory cytokine that plays an important role in cancer pathogenesis. The present study was designed to investigate the possible associations among IL-17A genetic polymorphisms, EGFR mutation status, and the clinicopathologic development of LUAD in a Taiwanese population. Our study population consisted of 277 LUAD patients harboring the wild-type (WT) EGFR or a mutant (MT) EGFR. Four single-nucleotide polymorphisms (SNPs) of IL-17A in the peripheral blood, including rs8193036(C > T), rs8193037(G > A), rs2275913(G > A), and rs3748067(C > T) loci, were genotyped using a TaqMan allelic discrimination assay. Our results showed that none of these IL-17A SNPs were correlated with the risk of developing mutant EGFR. However, patients with a smoking habit who carried the GA genotype of IL-17A rs8193037 had a significantly lower susceptibility to EGFR mutations (adjusted odds ratio (AOR): 0.225; 95% confidence interval (CI): 0.056~0.900, p = 0.035). Moreover, compared to individuals carrying the CC genotype of rs8193036 at IL-17A, T-allele carriers (CT + TT) were at higher risk of developing more-advanced stages (stage III or IV; p = 0.020). In the WT EGFR subgroup analysis, IL-17A rs8193036 T-allele carriers had higher risks of developing an advanced tumor stage (p = 0.016) and lymphatic invasion (p = 0.049). Further analyses of clinical datasets revealed correlations of IL-17 receptor A (IL-17RA) and IL-17RC expressions with a poor prognosis of LUAD patients with a smoking history or with higher levels of tumor-infiltrating lymphocytes. In conclusion, our results suggested that two functional promoter polymorphisms of IL-17A, i.e., rs8193036 and rs8193037, were associated with the EGFR mutation status and progression in LUAD patients, indicating that these two genetic variants might act as possible markers for predicting patients’ clinical prognoses.

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