Identification of Genetic Variants Associated with Sex-Specific Lung-Cancer Risk

Background: The incidence of lung cancer differs between men and women, suggesting the potential role of sex-specific influences in susceptibility to this cancer. While behavioural differences may account for some of the risk, another possibility is that X chromosome susceptibility genes may have an effect. Little is known about genetic variants on the X chromosome that contribute to sex-specific lung-cancer risk, so we investigated this in a previously characterized cohort. Methods: We conducted a genetic association reanalysis of 518 lung cancer patients and 844 controls to test for lung cancer susceptibility variants on the X chromosome. Annotated gene expression, co-expression analysis, pathway, and immune infiltration analyses were also performed. Results: 24 SNPs were identified as significantly associated with male, but not female, lung cancer cases. These resided in blocks near the annotated genes DMD, PTCHD1-AS, and AL008633.1. Of these, DMD was differentially expressed in lung cancer cases curated in The Cancer Genome Atlas. A functional enrichment and a KEGG pathway analysis of co-expressed genes revealed that differences in immune function could play a role in sex-specific susceptibility. Conclusions: Our analyses identified potential genetic variants associated with sex-specific lung cancer risk. Integrating GWAS and RNA-sequencing data revealed potential targets for lung cancer prevention.

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Association between polymorphism in CDKN2B-AS1 gene and its interaction with smoking on the risk of lung cancer in a Chinese population

Human Genomics ◽

10.1186/s40246-019-0240-4 ◽

2019 ◽

Vol 13 (1) ◽

Cited By ~ 2

Author(s):

Xiaoting Lv ◽

Zhigang Cui ◽

Hang Li ◽

Juan Li ◽

Zitai Yang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Case Control Study ◽

Lung Cancer Risk ◽

Cancer Susceptibility ◽

Lung Squamous Cell Carcinoma ◽

Case Control ◽

Recessive Model ◽

Lung Cancer Patients ◽

Control Study

Abstract Background Long non-coding RNAs became the hot spots in the carcinogenesis of various tumors. This case-control study evaluated the association between the rs2151280 in lncRNA CDKN2B-AS1 and lung cancer risk. Methods This study included 507 lung cancer patients and 542 healthy individuals. Odds ratios and their 95% confidence intervals were calculated by unconditional logistic regression analysis to evaluate the association between the rs2151280 and lung cancer risk. Results Compared with individuals carrying TT genotype, individuals carrying CC genotype of rs2151280 had a decreased risk of lung cancer (OR = 0.640, 95%CI = 0.421–0.972, P = 0.036). In the recessive model, rs2151280 CC genotype was observed to reduce the risk of lung cancer (OR = 0.684). C allele was associated with non-small cell lung cancer risk (OR = 0.674). The rs2151280 was significantly associated with lung adenocarcinoma risk (CCvsTT: OR = 0.567, 95%CI = 0.333–0.965, P = 0.037; CCvsTC+TT: OR = 0.543, 95%CI 0.330–0.893, P = 0.016, respectively). However, there was no significant association between rs2151280 and lung squamous cell carcinoma risk in five models. The quantitative analysis suggested that there were no significant interactions of rs2151280 with smoking exposure to lung cancer susceptibility. Conclusions This hospital-based case-control study suggested that CDKN2B-AS1 rs2151280 T>C was associated with the risk of lung cancer.

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miR-146a and miR-196a-2 genes polymorphisms and its circulating levels in lung cancer patients

The Journal of Biochemistry ◽

10.1093/jb/mvz044 ◽

2019 ◽

Vol 166 (4) ◽

pp. 323-329 ◽

Cited By ~ 2

Author(s):

Randa H Mohamed ◽

Heba F Pasha ◽

Doaa M Gad ◽

Mostafa M Toam

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Cancer Patients ◽

Lung Cancer Risk ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Lung Cancer Patients ◽

Increased Risk ◽

Increase Risk ◽

Circulating Levels

AbstractRecently, MicroRNAs polymorphisms and their serum expression have been linked to increase risk of various cancers. The aim of this study was to elucidate the association between single nucleotide polymorphisms of miR-146a and miR-196a-2 and their serum expression and lung cancer risk. One hundred and twenty lung cancer patients and 120 health controls were included in this study. Genotyping and expression for miR-146a and miR-196a-2 were performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and quantitative real-time PCR. Individuals carrying miR-146a CG and CC genotypes had significantly increased risk for lung cancer than those carrying miR-146a GG genotype. MiR-146a expression significantly decreased in miR-146a CG and CC genotypes carriers as compared with GG genotype carriers. MiR-196a-2 CT and TT genotypes were significantly associated with increased lung cancer while the highest expression of MiR-196a-2 was detected in miR-196a-2 CC genotype carriers. Serum miR-146a was significantly decreased in lung cancer patients while serum miR-196a-2 expression was significantly increased in lung cancer patients. In conclusion, miR-146a and miR-196a-2 genes polymorphisms and their circulating levels were associated with lung cancer risk in Egyptians and may be helpful in early detection of lung cancer.

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Analysis of Erythrocyte Glycophorin-A Variants by Flow Cytometry in Lung Disease Patients Detects the Effect of Tobacco Smoke

Analytical Cellular Pathology ◽

10.1155/2000/512786 ◽

2000 ◽

Vol 21 (1) ◽

pp. 35-40 ◽

Cited By ~ 2

Author(s):

Monica Neri ◽

Elio Geido ◽

Rosangela Filiberti ◽

Roberto Orecchia ◽

Angela Di Vinci ◽

...

Keyword(s):

Lung Cancer ◽

Flow Cytometry ◽

Cancer Risk ◽

Tobacco Smoke ◽

Lung Cancer Risk ◽

Small Population ◽

Cancer Risk Assessment ◽

Lung Cancer Patients ◽

Increased Risk

The glycophoryn A (GPA) assay evaluates somaticin vivomutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment.GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies.We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer.There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p< 0:01). No association was shown with occupational exposure.The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.

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The rs28757157 and rs59429575 polymorphisms in CYP19A1 are associated with lung cancer in Chinese Han population

10.21203/rs.3.rs-25248/v3 ◽

2020 ◽

Author(s):

Chan Zhang ◽

Yujing Cheng ◽

Wanlu Chen ◽

Qi Li ◽

Run Dai ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Lung Cancer Risk ◽

Genetic Model ◽

Protective Role ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population ◽

Lung Cancer Patients ◽

Functional Studies

Abstract Background: Lung cancer is the leading cause of cancer death globally. Recent studies have revealed that the CYP19A1 gene played a crucial role in cancer initiation and development. The aim of this study was to assess the association of CYP19A1 genetic polymorphisms with the risk of lung cancer in the Chinese Han population. Method: This study randomly recruited 507 lung cancer patients and 505 healthy controls. The genotypes of four SNPs of CYP19A1 gene were identified by Agena MassARRY technique. Genetic model analysis was used to assess the association between genetic variation and lung cancer risk. Odds ratio (OR) values and 95% confidence intervals (CIs) were provided for the evaluation of the lung cancer risk effect. Results: Rs28757157 and rs59429575 polymorphisms of CYP19A1 were significantly correlated with the risk of lung cancer. In stratified analysis, rs28757157 was associated with increased cancer risk in smokers and individuals aged ≤ 60 years. Meanwhile, rs59429575 was identified as a risk biomarker in females and lung adenocarcinoma patients (p < 0.05). While rs28757157 exerted a protective role among people with a BMI greater than 24 (p = 0.033). Conclusions: This study identified two new SNPs (rs28757157 and rs59429575) of CYP19A1 associated with lung cancer in Chinese Han population. These findings provide data support for further functional studies of CYP19A1 in lung cancer.

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Ethnic differences in allele, genotype distributions and lung cancer risk of polymorphisms of gemcitabine metabolic pathway genes in south Indian population

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20183463 ◽

2018 ◽

Vol 7 (9) ◽

pp. 1693

Author(s):

Devika Tirumalasetty ◽

Deepak Gopal Shewade ◽

Biswajit Dubashi ◽

Srinivasa Rao Katiboina

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Metabolic Pathway ◽

Lung Cancer Risk ◽

Allele Frequencies ◽

Healthy Population ◽

South Indian Population ◽

Lung Cancer Patients ◽

South Indian ◽

Significant Difference

Background: Gemcitabine is a widely used cytotoxic drug in the treatment of a number of solid tumors, for instance, lung, pancreatic as well as breast cancer. As a consequence of the progressive genomic instability, the efficiency rates have eventually lowered. Genetic approach targeting one or several genes in drug targeting pathways facilitates substantially more valuable details in explaining the association between variants and also the efficacy of gemcitabine therapy. In addition, several researchers have reported ethnic discrepancies in clinical response to gemcitabine. Thus, the present study was aimed to establish the normative frequencies of genes associated with the metabolic pathway of Gemcitabine (RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA 435 C>T (rs1048977) in South Indian healthy population and compared with 1000 genome population. Additionally, the association of these SNPs with the risk of developing lung cancer was also evaluated.Methods: This study was carried out on 184 healthy subjects and 123 lung cancer patients of South Indian origin and genotyping was done using RT-PCR (Real Time Polymerase Chain Reaction). The frequencies of the above polymorphisms were in Hardy-Weinberg equilibrium (p >0 .05).Results: The minor allele frequencies of the SNPs RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA -435 C>T (rs1048977) were 31.3, 36.7, 24.5 and 22.0 respectively.Conclusions: There was a significant difference observed between the genotype and allele frequencies of south Indians with the 1000 genome populations. We also found that SNPs of RRM1 were significantly associated with lung cancer risk.

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Abstract 4596: Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: A report from the Female Lung Cancer Consortium in Asia

10.1158/1538-7445.am2015-4596 ◽

2015 ◽

Cited By ~ 1

Author(s):

Mitchell J. Machiela ◽

Chao A. Hsiung ◽

Xiao-Ou Shu ◽

Wei J. Seow ◽

Zhaoming Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Telomere Length ◽

Genetic Variants ◽

Lung Cancer Risk ◽

Female Lung Cancer

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Immunoassayofantibodies to benzo[a]pyrene, estradiol and progesterone fordeterminationofpersonal lung cancer riskinmen

Siberian Journal of Oncology ◽

10.21294/1814-4861-2019-18-2-35-43 ◽

2019 ◽

Vol 18 (2) ◽

pp. 35-43

Author(s):

A. N. Glushkov ◽

E. G. Polenok ◽

S. A. Mun ◽

L. A. Gordeeva ◽

M. V. Kostyanko ◽

...

Keyword(s):

Lung Cancer ◽

Risk Assessment ◽

Cancer Risk ◽

Blood Serum ◽

Lung Cancer Risk ◽

Cancer Risk Assessment ◽

Serum Antibodies ◽

Healthy Men ◽

Lung Cancer Patients

A personalized lung cancer risk assessment is important for disease prevention.The aim of the studywas to estimate a significance of immunoanalysis of antibodies to benzo[a]pyrene, estradiol and progesterone for lung cancer risk prediction in men with respect to age and smoking.Material and methods. Serum antibodies to benzo[a]pyrene, estradiol and progesterone in the blood serum of 620 healthy men (279 smokers) and 827 lung cancer patients (627 smokers) were studied using semi-quantitative enzyme immunoassay.Results. The high lung cancer risk was observed in smokers aged over 55 years: oR=15.4 (11.5–20.8 95 % ci). the lung cancer risk in this group of patients was significantly lower when their levels of antibodies to benzo[a]pyrene and to estradiol were lower than those to progesterone: oR=3.2 (2.0–5.0). the lung cancer risk was higher when the personal levels of antibodies to benzo[a]pyrene and to estradiol were higher than the levels of antibodies to progesterone: oR=20.0 (10.5–38.1).Conclusion. The immunoassay of the blood serum antibodies specific to benzo[a]pyrene, estradiol and progesterone could be useful for determination of the lung cancer risk in men.

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Influence of CMTM8 polymorphisms on Lung Cancer Susceptibility in the Chinese Han Population

10.21203/rs.3.rs-34577/v1 ◽

2020 ◽

Author(s):

Jiamin Wu ◽

Yao Sun ◽

Zichao Xiong ◽

Fanglin Niu ◽

Yuanwei Liu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Risk ◽

Cancer Patients ◽

Lung Cancer Risk ◽

Lung Squamous Cell Carcinoma ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population ◽

Lung Cancer Patients ◽

Increased Risk

Abstract Objective: Lung cancer is the leading cause of cancer-related mortality worldwide and CMTM8 is a potential tumor suppressor gene, which is down-regulated in lung cancer. The objective of this research was to assess the association of CMTM8 genetic polymorphisms with lung cancer risk in Chinese Han population.Methods: To evaluate the correlation between CMTM8 polymorphisms and lung cancer risk, Agena MassArray platform was used for genotype determination among 509 lung cancer patients and 506 controls. Multiple genetic models, stratification analysis and haploview analysis was used by calculating odds ratio (OR) and 95% confidence intervals (CIs).Results: Significant associations were detected between CMTM8 rs6771238 and an increased lung cancer risk in codominant (adjusted OR = 1.57, 95%CI: 1.01-2.42, p = 0.044) and dominant (adjusted OR = 1.54, 95%CI: 1.01-2.36, p = 0.047)models. After gender stratification analysis,weobserved that rs6771238 was related to an increased risk of lung squamous cell carcinoma, while rs6771238 was associated with anincreased risk of lung adenocarcinoma. Rs9835916 and rs1077868 were correlated with lung cancer staging.Rs9835916 was linked to increased risk of lymph node metastasis in lung cancer patients. Conclusions: Our study firstly reported that the CMTM8 polymorphisms were a risk factors for lung cancer, which suggested the potential roles of CMTM8 in the development of lung cancerin Chinese Han population.

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