Lung Cancer Susceptibility Research Articles

Relationship between CYP1B1 polymorphisms (c.142C > G, c.355G > T, c.1294C > G) and lung cancer risk in Polish smokers.

To determine whether three of CYP1B1 single nucleotide polymorphisms, c.142C>G, c.355G>T and c.1294C>G are associated with a lung cancer risk. A total of112 lung cancer patients and 100 controls were genotyped using the RFLP-PCR. In the c.142C>G polymorphisms, G allele was more frequent in lung cancer patients than in controls (p<0.001), while in the c.1294C>G polymorphisms, C allele was more frequent in lung cancer patients, than in controls (p=0.012). In the c.355G>T polymorphism, the distribution of alleles in both analyzed groups was similar. The GTC haplotype turned out to be correlated with the increased lung cancer risk, compared with the most common CGG haplotype (OR: 2.38; p=0.001). CYP1B1 gene polymorphisms appear to influence lung cancer susceptibility.

Fine mapping in TERT-CLPTM1L region identified three independent lung cancer susceptibility signals: A large-scale multi-ethnic population study.

Genome-wide association studies (GWAS) and fine mapping studies have identified multiple lung cancer susceptibility variants in TERT-CLPTM1L region. However, it is still unclear about the relationship between these risk variants and the independent lung cancer risk signals in this region. Therefore, we evaluated the independent susceptibility signals for lung cancer and explored the potential functional variants in this region. Sequential conditional analysis was used to detect the independent susceptibility loci based on four lung cancer GWAS datasets with 12 843 lung cases and 12 639 controls. Comprehensively functional annotations were performed for each independent signal. Three independent susceptibility signals were identified in multi-ethnic population. For the first signal, rs2736100 showed the most significant association with lung cancer risk (C > A, OR = 0.82, 95%CI: 0.79-0.85, P = 1.98 × 10-25 ). Rs36019446 was the top-ranked site (A > G, OR = 0.88, 95%CI: 0.84-0.92, P = 1.74 × 10-9 ) in the second signal. For the third signal, rs326048 was the leading SNP (A > G, OR = 0.91, 95%CI: 0.87-0.95, P = 1.38 × 10-5 ). The following subgroup analysis found the same three loci among Asian population. Further, we compared the difference between various subgroup populations. Functional annotations revealed that rs2736100, rs27996 (r2 = 0.85 with rs36019446) and rs326049 (r2 = 0.73 with rs326048) could be potential functional variants in these three risk signals, respectively. In conclusion, although multiple variants have been found associated with lung cancer risk in TERT-CLPTM1L region, our findings indicated that there are three independent lung cancer susceptibility signals in this region.

Rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT expression instead of CLPTM1L in East Asian populations.

Lung cancer is a common cancer in human and has presented significant genetic predisposition. Previous genome-wide association study observed that rs401681 within CLPTM1L (CLPTM1 like) was significantly associated with lung cancer. By analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby region, rs402710, in high linkage disequilibrium with rs401681, which was also associated with lung cancer. However, the real causal SNP and mechanism for the association were still not clear. The following plasmid construction, mutagenesis, transient transfection and luciferase reading indicated that both SNPs could regulate gene expression in lung/bronchial epithelium Beas-2B cell line. By chromosome conformation capture, it was identified that the segment containing these two SNPs could interact with TERT (telomerase reverse transcriptase) promoter, thus indicating that these SNPs confer lung cancer risk by regulating TERT expression instead of CLPTM1L. Through chromatin immunoprecipitation, the transcript factors HNF4A (hepatocyte nuclear factor 4 alpha) and MAF1 (MAF1 homolog, negative regulator of RNA polymerase III) were recognized for the regions spanning rs401681 and rs402710, respectively. Our results uncovered a complete link between these two SNPs and lung cancer.

Association between VEGF Gene Polymorphisms and the Susceptibility to Lung Cancer: An Updated Meta-Analysis.

Background and Objective The association between vascular endothelial growth factor (VEGF) gene polymorphisms (-2578C/A, +936C/T, and -460C/T) and lung cancer risk has been extensively studied in the last decades, but currently available results remain controversial or ambiguous. Therefore, we conducted a meta-analysis to assess whether the relationship between the VEGF gene and lung cancer susceptibility exists. Methods The meta-analysis was conducted by searching the databases PubMed, Embase, and Web of Science covering all eligible studies published up to October 1, 2017. The pooled odds ratios (ORs) as well as their 95% confidence intervals (CIs) were utilized to evaluate the possible associations. Publication bias of relevant studies was examined via Begg's funnel plots and Egger's regression tests. Results This meta-analysis included 13 published case–control studies covering 4477 patients with lung cancer and 4346 healthy controls, who had been accrued from December 1992 to July 2012. For the overall eligible data collected in our meta-analysis, it indicated that VEGF +936C/T, -460C/T, and -2578C/A polymorphisms did not correlate with the elevated lung cancer risk in all genetic comparison models. Moreover, VEGF +460T/C polymorphism was found to be significantly associated with susceptibility to lung cancer in these models (allele model: pooled OR = 1.12, 95% CI: 1.00–1.26, P = 0.184; homozygote model: pooled OR = 1.51, 95% CI: 1.12–2.03, P = 0.821), but no significant results were detected in Caucasian populations. Conclusions VEGF +936C/T, -460C/T, and -2578C/A polymorphisms were not associated with the risk of lung cancer. The VEGF +460T/C polymorphism might be a risk factor for lung cancer only in Asian populations.

A Meta-Analysis of miR-499 rs3746444 Polymorphism for Cancer Risk of Different Systems: Evidence From 65 Case-Control Studies.

MicroRNAs (miRNAs) are a class of endogenous, short and non-coding RNAs that may play important roles in the pathogenesis of tumor. The associations between microRNA-499 rs3746444 polymorphism and cancer risk in different systems remain inconclusive. This article is aimed to obtain more exact estimation of these relationships through a meta-analysis based on 52,456 individuals. We retrieved relevant and eligible studies from Pubmed and Embase database up to January 10, 2018. ORs and 95% CIs were used to estimate the associations between miR-499 polymorphism and cancer susceptibility in different systems. All analyses were performed using the Stata 11.0 software. A total of 65 case-control studies were retrieved using explicit inclusion and exclusion criteria. The study included 23,762 cases and 28,694 controls. Overall cancer analysis showed the association between miR-499 polymorphism and susceptibility to cancer was significant. MicroRNA-499 rs3746444 was found to be significantly associated with increased risk of cancer of the respiratory system (CC vs. TT: OR = 1.575, 95% CI = 1.268–1.955, CC vs. TC+TT: OR = 1.527, 95% CI = 1.232–1.892), digestive system (CC vs. TT: OR = 1.153, 95% CI = 1.027–1.295; TC vs. TT: OR = 1.109, 95% CI = 1.046–1.176; CC+TC vs. TT: OR = 1.112, 95% CI = 1.018–1.216; CC vs. TC+TT: OR = 1.137, 95% CI = 1.016–1.272; C vs. T: OR = 1.112, 95% CI = 1.025–1.206), urinary system (TC vs. TT: OR = 1.307, 95% CI = 1.130–1.512; CC+TC vs. TT: OR = 1.259, 95% CI = 1.097–1.446; C vs. T: OR = 1.132, 95% CI = 1.014–1.264), and gynecological system (C vs. T: OR = 1.169, 95% CI = 1.002–1.364). In the subgroup analysis by ethnicity, the result showed that significant association with an increased cancer risk was found in Asian. Subgroup analysis based on type of tumor was also performed, miR-499 rs3746444 is associated with susceptibility of cervical squamous cell carcinoma, lung cancer, prostate cancer, and hepatocellular carcinoma.

Functional Polymorphism in the MSI1 Gene Promoter Confers a Decreased Risk of Lung Cancer in Chinese by Reducing MSI1 Expression.

Background: Musashi1 (MSI1) is a characteristic stem cell marker that regulates the balance between cell self-renewal and differentiation. Evidence has identified MSI1 as a pivotal oncogenic regulator in diverse malignancies. However, little evidence uncovers the role of genetic variations of MSI1 gene in cancer etiology.Objective: The aim of this study was to investigate the association between genetic variants in the MSI1 gene and lung cancer risk.Methods: Based on a two-stage retrospective study with a total of 1559 patients with lung cancer and 1667 healthy controls, we evaluated the relevance between three putative functional SNPs in the MSI1 promoter (i.e., -2696T>C[rs7959801], -2297T>C[rs3742038] and -1081C>T[rs34570155]) and lung cancer risk.Results: We found that the SNP rs7959801T>C was significantly associated with lung cancer susceptibility. Compared to those with rs7959801TT wild-genotype, individuals with CT/CC variant genotypes exerted consistently beneficial roles in lung cancer risk in the discovery set (adjusted odd ratios [OR] = 0.67; 95% confidence interval [CI] = 0.57-0.80), and in the validation set (OR=0.69; 95%CI=0.54-0.88). Functional assays indicated that the allele transformation from T to C in rs7959801 of MSI1 gene arrestingly decreased its transcription activity in vitro. Furthermore, the expression levels of MSI1 were significantly lower in the patients with CT/CC variants than in those who were with TT genotype.Conclusion: Our findings suggested that the rs7959801T>C polymorphism in the MSI1 promoter conferred a decreased risk to lung cancer by reducing the expression of MSI1 and it may be a promising indicator for lung cancer predisposition.

Functional miRNA variants affect lung cancer susceptibility and platinum-based chemotherapy response.

Platinum-based chemotherapy is widely used as the first-line treatment of lung cancer. MicroRNAs have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in miRNA involved in miRNA biogenesis and structural alteration may affect miRNA expression. In this study, we aimed to investigate the association of functional miRNA variants with the lung cancer susceptibility and platinum-based chemotherapy response. Nine genetic polymorphisms in miR-605, 146a, 149, 196a-2, 27a, 499, 30c-1, 5197 and let-7a-2 were selected with comprehensive collection strategy and genotyped by MALDI-TOF mass spectrometry in a total of 215 health control and 507 lung cancer patients (386 patients received at least two consecutive cycles of platinum-based chemotherapy). We found that an allele carriers of miR-146a rs2910164 (P=0.022, OR=1.315) and C allele carriers of miR-149 rs71428439 (P=0.042, OR=1.372) performance a high risk of lung cancer. Mir-30c-1 rs928508 (P=0.005, in recessive model) and let-7a-2 rs629367 (P=0.030 and P=0.021, in additive and dominant models, respectively) showed strong relationship with lung cancer risk in age under 57 years. The rs11614913 (miR-196a-2) C allele or rs9280508 (miR-30c-1) G allele carriers shown more sensitive to platinum both in additive (P=0.010, P=0.022, respectively) and dominant models (P=0.001, P=0.018, respectively). These findings suggested that SNPs rs71428439 (miR-149), rs2910164 (miR-146a), rs928508 (mir-30c-1) and rs629367 (let-7a-2) were associated with the lung cancer prevalence, polymorphisms of rs11614913 (miR-196a-2) and rs9280508 (miR-30c-1) significantly influenced the patients' response to platinum-based chemotherapy, which may serve as potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.

Effect of HOTAIR rs12826786 and rs1899663 polymorphisms on lung cancer susceptibility and clinicopathological characteristics in a turkish population: a hospital-based case-control study

Overexpression of Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with tumorigenesis and multiple cancer types including lung cancer. In this study, the association between two HOTAIR single nucleotide polymorphisms (SNPs) (rs12826786 and rs1899663) on the risk and clinical characteristics of lung cancer in a Turkish population was investigated. We genotyped HOTAIR rs12826786 and rs1899663 polymorphisms in 180 Turkish people including 87 lung cancer patients (71 males and 16 females) and 93 age-matched healthy controls (67 males and 26 females) by a TaqMan real-time polymerase chain reaction method. The mean age value of the lung cancer patients and control subjects were 59.27 ± 10.55 and 61.77 ± 12.00, respectively. We found that none of the two HOTAIR polymorphisms (rs12826786 T&gt;C, rs1899663A&gt;C) has any significant association with the increased risk of lung cancer in any type of inheritance genetic models. However, our research indicated that carriers of Trs12826786/Crs1899663 (ht3) (P = 0.03) had an increased risk of lung cancer susceptibility.

CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: A meta-analysis involving 10,947 subjects.

The above article, published in the Journal of Cellular and Molecular Medicine on 14 September 2016 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 19, pp. 2136‐2142, has been retracted by agreement between the authors, the journal Editor in Chief, Stefan Constantinescu, and John Wiley & Sons Ltd. The retraction has been agreed due to unattributed overlap of the language used in the “Materials and method” and “Discussion” sections of this study and the following article published in Lung Cancer: “CYP2E1 Rsa I/Pst I polymorphism is associated with lung cancer risk among Asians” by Ping Zhan, Jing Wang, Yu Zhang, Li‐Xin Qiu, Su‐feng Zhao, Qian Qian, Shu‐Zhen Wei, Li‐Ke Yu and Yong Song, Volume 69, 2010, pages 19‐25. REFERENCE Shen Z‐T, Wu X‐H, Li B, Shen J‐S, Wang Z, Li J, Zhu X‐X. CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: a meta‐analysis involving 10,947 subjects. J Cell Mol Med. 2015;19:2136‐2142. https://doi.org/10.1111/jcmm.12579

XPF polymorphism toward lung cancer susceptibility and survival in patients treated with platinum-based chemotherapy.

To evaluate the association of three XPF polymorphic variants (673 C>T, 11985 A>G, G415A) with lung cancer, overall survival and clinical response in North Indians. Genotyping was performed using PCR-restriction fragment length polymorphism. A total of 673 C>T polymorphism was associated with 1.5-fold increased lung cancer risk for heterozygous genotype (CT; p=0.03). Adenocarcinoma patients with 673 C>T polymorphism carrying heterozygous genotype (CT) had a lower hazard ratio (p=0.01). Classification and regression tree analysis predicted XPF 673 C>T (M) as the strongest risk factor for the lung cancer (p=0.003). For 11985 A>G polymorphism, lung cancer subjects treated with irinotecan cisplatin/carboplatin regimen having heterozygous genotype (AG) was associated with high mortality risk (p=0.0001). 673 C>T polymorphism was associated with increased lung cancer risk.

Combining ctnnb1 genetic variability with epidemiologic factors to predict lung cancer susceptibility.

Early detection and diagnosis of lung cancer remain challenging but would improve patient prognosis. The goal of this study is to develop a model to estimate the risk of lung cancer for a given individual. We conducted a case-control study to develop a predictive model to identify individuals at high risk for lung cancer. Clinical data from 500 lung cancer patients and 500 population-based age- and gender-matched controls were used to develop and evaluate the model. Associations between environmental variants together with single nucleotide polymorphisms (SNPs) of beta-catenin (ctnnb1) and lung cancer risk were analyzed using a logistic regression model. The predictive accuracy of the model was determined by calculating the area under the receiver operating characteristic (ROC) curve. Prior diagnosis of chronic obstructive pulmonary disease (COPD), pulmonary tuberculosis, family history of cancer, and smoking are lung cancer risk factors. The area under the curve (AUC) was 0.740, and the sensitivity, specificity, and Youden index were 0.718, 0.660, and 0.378, respectively. Our risk prediction model for lung cancer is useful for distinguishing high-risk individuals.

Correction: Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells.

[This corrects the article DOI: 10.1371/journal.pone.0184922.].

The Role of Interleukin-31 Polymorphisms in Non-Small Cell Lung Cancer Genetic Susceptibility and Clinical Outcome.

Interleukin-31 (IL-31), a novel T helper type 2 effector cytokine, is known to have an important effect on the pathogenesis of allergic disease and tumors. However, the impact of IL-31 on human lung cancer remains unclear. This study explored the role of IL-31 polymorphisms in lung cancer and sought to characterize how IL-31 polymorphisms correlate with lung cancer tumorigenesis and patient survival rates. Using a single-nucleotide polymorphism genotype assay, we examined the expression of two IL-31 polymorphisms (rs7977932 and rs4758680) in samples from 302 lung cancer patients and 493 control cases. Lung cancer patients who were homozygous CC for rs7977932 or carried the G allele of rs4758680 had significantly poorer prognoses compared to those who did not have these genotypes. Moreover, the rs7977932 CC genotype was significantly associated with metastasis and poor survival status in lung adenocarcinoma. Our study indicates the importance of IL-31 polymorphisms for susceptibility and survival status in lung cancer.

A Decade of GWAS Results in Lung Cancer.

Genome-wide association studies (GWAS) were successful to identify genetic factors robustly associated with lung cancer. This review aims to synthesize the literature in this field and accelerate the translation of GWAS discoveries into results that are closer to clinical applications. A chronologic presentation of published GWAS on lung cancer susceptibility, survival, and response to treatment is presented. The most important results are tabulated to provide a concise overview in one read. GWAS have reported 45 lung cancer susceptibility loci with varying strength of evidence and highlighted suspected causal genes at each locus. Some genetic risk loci have been refined to more homogeneous subgroups of lung cancer patients in terms of histologic subtypes, smoking status, gender, and ethnicity. Overall, these discoveries are an important step for future development of new therapeutic targets and biomarkers to personalize and improve the quality of care for patients. GWAS results are on the edge of offering new tools for targeted screening in high-risk individuals, but more research is needed if GWAS are to pay off the investment. Complementary genomic datasets and functional studies are needed to refine the underlying molecular mechanisms of lung cancer preliminarily revealed by GWAS and reach results that are medically actionable. Cancer Epidemiol Biomarkers Prev; 27(4); 363-79. ©2018 AACRSee all articles in this CEBP Focus section, "Genome-Wide Association Studies in Cancer."

A meta-analytic review of the association between two common SNPs in miRNAs and lung cancer susceptibility.

BackgroundMicroRNAs (miRNAs) are involved in many biological processes, including tumor suppression. Multiple studies have shown an association between the miRNA-196a2 rs11614913 and miRNA-146a rs2910164 polymorphisms and cancer risk. However, the implications of the reported data are debatable and inconclusive.Materials and methodsRelevant articles were retrieved from the PubMed, EMBASE, China National Knowledge Infrastructure, and WanFang databases from January 1, 2007, to April 30, 2017. Studies were assessed based on designated inclusion and exclusion criteria, and data were manually extracted from relevant studies by two investigators. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to explore the association between two single-nucleotide polymorphisms (SNPs) in miRNAs and lung cancer susceptibility.ResultsNine eligible articles were included, consisting of 3,101 cancer cases and 3,234 controls for miRNA-196a2 rs11614913, and 3,483 cases and 3,578 controls for miRNA-146a rs2910164. For studies evaluating miRNA-196a2 rs11614913, significant associations with lung cancer risk were discovered. Overall, the pooled analysis showed that miRNA-196a2 rs11614913 was associated with a decreased cancer risk (CC vs TT: OR = 1.25, 95% CI: 1.09–1.44; CT vs TT: OR = 1.26, 95% CI: 1.03–1.53). For miRNA-146a rs2910164, only the CC genotype was found to be associated with high lung cancer risk (OR = 1.30, 95% CI: 1.13–1.49). Subgroup analyses based on ethnicity, source of control group, and country indicated that there were strong associations between miRNA-146a rs2910164 and cancer risk.ConclusionThe results indicated that lung cancer risk was significantly associated with miRNA-196a2 rs11614913 and miRNA-146a rs2910164. These two common SNPs in miRNAs may be potential biomarkers of lung cancer.

TRAP1 Inhibition Increases Glutamine Synthetase Activity in Glutamine Auxotrophic Non-small Cell Lung Cancer Cells.

Cancer cells are distinct in terms of glutamine dependence. Here we investigated the different susceptibility of glutamine-independent and glutamine-dependent non-small cell lung cancer (NSCLC) to treatment with tumor necrosis factor receptor-associated protein 1 (TRAP1) inhibitor gamitrinib-triphenylphosphonium (G-TPP). Cell viability and proliferation under glutamine deprivation and G-TPP treatment were determined by the MTT and colony-formation assays. Protein and mRNA expression were determined by western blot and quantitative polymerase chain reaction. Colorimetric-based assay was performed to check for glutamine synthetase (GS) activity. NSCLC cells showed diverse adaptation under glutamine-depleted condition and were categorized into glutamine-independent and glutamine-dependent cells. Treatment with G-TPP particularly increased GS activity and induced cell death due to energy shortage indicated by phosphorylated AMP-activated protein kinase (AMPK) in glutamine-dependent cells. This finding provides better understanding of TRAP1-mediated glutamine metabolism through GS activity, and evidence that TRAP1 could be a promising therapeutic target for glutamine-addicted cancer.

Role of Sequence Variations in AhR Gene Towards Modulating Smoking Induced Lung Cancer Susceptibility in North Indian Population: A Multiple Interaction Analysis.

Background: AhR, a ubiquitously expressed ligand-activated transcription factor, upon its encounter with the foreign ligands activates the transcriptional machinery of genes encoding for bio-transformation enzymes like CYP1A1 hence, mediating the metabolism of Poly aromatic hydrocarbons and nitrosamines which account for the maximally found carcinogen in cigarette smoke. Polymorphic variants of AhR play a significant role and are held responsible for disposing the individuals with greater chances of acquiring lung cancer.Objective: To study the role of AhR variants (rs2282885, rs10250822, rs7811989, rs2066853) in affect-ing lung cancer susceptibility.Methods: 297 cases and 320 controls have been genotyped using PCR-RFLP technique. In order to find out the association, unconditional logistic regression approach was used. To analyze high order in-teractions Multifactor Dimensionality Reduction and Classification and regression tree was used.Results: Subjects carrying the variant genotype for AhR rs7811989 showed a two-fold risk (p=0.007) and a marginal risk was also seen in case of individuals carrying either single or double copy of suscep-tible allele for rs102550822 (p=0.02). Whereas the variant allele for rs2066853 showcased a strong pro-tective effect (p=0.003). SQCC individuals with mutant genotype of rs2066853 also exhibited a protec-tive effect towards lung cancer (OR=0.30, p=0.0013). The association of rs7811989 mutant genotype and rs10250822 mutant genotype was evident especially in smokers as compared to non-smokers. AhR rs2066853 showed a decreased risk in smokers with mutant genotype (p=0.002). MDR approach gave the best interaction model of AhR rs2066853 and smoking (CVC=10/10, prediction error=0.42).Conclusion: AhR polymorphic variations can significantly contribute towards lung cancer predisposi-tion.

Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR= 0.74, [95% confidence interval (CI): 0.58-0.94] and OR= 0.71 [95% CI: 0.50-1.01], respectively, p= 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR= 0.75 [95% CI: 0.59-0.95] and OR= 0.69 [95% CI: 0.46-1.03], respectively, p= 0.03). Survival was not influenced by genotype. This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer.

Collective effects of common SNPs and risk prediction in lung cancer

Lung cancer is the leading cause of cancer deaths in both men and women in the US. While most sporadic lung cancer cases are related to environmental factors such as smoking, genetic susceptibility may also play an important role and a number of lung cancer associated single-nucleotide polymorphisms (SNPs) have been identified although many remain to be found. The collective effects of genome-wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have been linked with quantitative variations of complex traits and diseases. Here we studied MAC in lung cancer using previously published SNPs data sets (US and Finland samples) and found higher MAC in cases relative to matched controls. A set of 5400 SNPs with MA (MAF < 0.5) more common in cases (P < 0.08) and linkage disequilibrium (LD) r2 = 0.3 was found to have the best predictive accuracy. These results identify higher MAC in lung cancer susceptibility and provide a meaningful genetic method to identify those at risk of lung cancer.

Association of XPA Polymorphisms Towards Lung Cancer Susceptibility and its Predictive Role in Overall Survival of North Indians.

The present study investigated the role of Xeroderma pigmentosum group A (XPA) polymorphism (A23G and G709A) with lung cancer risk and its association with overall survival in North Indians. 370 cases and 370 controls were investigated to evaluate association between XPA polymorphism (A23G and G709A) with lung cancer risk using logistic regression analysis. A follow-up study was also conducted for 291 lung cancer cases illustrating correlation between overall survival in lung cancer patients and XPA variants. GG genotype showed an increased lung cancer risk (p=0.0007) for A23G polymorphism whereas G709A polymorphism was associated with significant protective effect in heterozygous (AG) subjects (p=0.001). When stratified according to smoking status an increased risk for lung cancer was observed for GG genotype in A23G polymorphism (p=0.0002). A poor survival in females carrying variant genotype (GG) was observed (p=0.001; MST=4.16months) for A23G polymorphism. Adenocarcinoma patients with heterozygous genotype showed an increased hazard ratio (p=0.02) for A23G polymorphism. G709A was associated with a reduced hazard ratio marking a better survival among mutant females (HR 0.17; p=0.05; MST=18.63months). It can be concluded that A23G polymorphism might contribute to increased lung cancer risk in North Indian population emphasizing on poor survival among females. G709A polymorphism might result in protective effect in lung cancer subjects. The present study had a low sample size but it could act as reference for the large sample studies in future.