Gene–asbestos interaction in malignant pleural mesothelioma susceptibility

Tùnesi, Sara; Ferrante, Daniela; Mirabelli, Dario; Andorno, Silvano; Betti, Marta; Fiorito, Giovanni; Guarrera, Simonetta; Casalone, Elisabetta; Neri, Monica; Ugolini, Donatella; Bonassi, Stefano; Matullo, Giuseppe; Dianzani, Irma; Magnani, Corrado

doi:10.1093/carcin/bgv097

Cited by 35 publications

(36 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hardy-Weinberg equilibrium was reassessed for the 8 SNPs comparing the observed genotype frequencies with the expected frequencies using c 2 test with significance level at P < 0.05 (38). The Akaike Information Criterion (AIC) was calculated for each genetic model and the genetic model with the smallest AIC was selected (39).…”

Section: Discussionmentioning

confidence: 99%

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population

Xiao¹,

Liu²,

Wen³

et al. 2019

Cancer Prevention Research

View full text Add to dashboard Cite

Persistent high-risk HPV infection is considered as a major cause of cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The RIG-I pathway in innate immunity plays an important role in antivirus response. Here, we hypothesized that altered function of mitochondrial antiviral signaling protein (MAVS) and mitochondrial TNF receptorassociated factor 3(TRAF3), key molecules downstream of the viral sensors RIG-I, may impair their ability of clearing HPV and thereby influence the risk for cervical precancerous lesions. To investigate the effects of MAVS and TRAF3 polymorphisms on susceptibility to cervical precancerous lesions, 8 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-environment interactions were also calculated. We found that CA genotype of rs6052130 in MAVS gene were at 1.48 times higher risk of developing cervical precancerous lesion than individuals with CC genotype (CA vs. CC: OR adjusted ¼ 1.48, 95% CI, 1.02-2.16). In addition, a significant synergetic interaction between high-risk HPV infection and rs6052130 was found on an additive scale. A significantly decreased risk of cervical precancerous lesions for the TC genotype of rs12435483 in the TRAF3 gene (OR adjusted ¼ 0.67, 95% CI, 0.45-0.98) was also found. Moreover, MDR analysis identified a significant three-locus interaction model, involving high-risk HPV infection, TRAF3 rs12435483 and number of full-term pregnancies. Our results indicate that the MAVS rs6052130 and TRAF3 rs12435483 confer genetic susceptibility to cervical precancerous lesions. Moreover, MAVS rs6052130-mutant individuals have an increased vulnerability to high-risk HPV-induced cervical precancerous lesions.

show abstract

Section: Discussionmentioning

confidence: 99%

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population

Xiao¹,

Liu²,

Wen³

et al. 2019

Cancer Prevention Research

View full text Add to dashboard Cite

show abstract

“…But, the study has some limitations, such asthe small sample size, the age unbalanced control group and the possible rare genetics variants that could have been excluded from the GWAS statistical analysis. 17 The MMP2 rs243865, T allele genotypes seem to have a protective role in predominantly thoracic malignancies, such as lung cancer and MM. Moreover, thoracic malignancies are also well known to have a strong environmental component (eg.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Štrbac¹,

Goričar²,

Dolžan³

et al. 2018

Radiology and Oncology

View full text Add to dashboard Cite

Patients and methods. The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%-75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).Results. Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44-1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35-0.86; P = 0.009).None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma.Conclusions. The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.

show abstract

“…The additive interaction between the factors was subsequently evaluated according to the following strategy (22). Among case and control subjects, a binary classification was used for the HPV infection (infection vs. non-infection) and the genotypes (homozygous for the major allele vs. one or two copies of the minor allele).…”

Section: Methodsmentioning

confidence: 99%

Interactions between polymorphisms in the 3′untranslated region of the cyclin dependent kinase 6 gene and the human papillomavirus infection, and risk of cervical precancerous lesions

Jing

Zhong³

et al. 2017

Biomedical Reports

View full text Add to dashboard Cite

The human papillomavirus (HPV) infection is essential for the development of cervical cancer and its precursor lesions. However, only certain persistently infected individuals develop cervical cancer. Cyclin-dependent kinase 6 (CDK6) is a critical regulatory cancer-associated gene in the cell cycle and in tumorigenesis. Single nucleotide polymorphisms (SNPs) in microRNA sites in the 3′-untranslated region (UTR) of target genes may result in target gene expression level changes and susceptibility to diseases, including cancer. Therefore, the aim of the present study was to determine whether SNPs in the 3′UTR of the CDK6 gene may affect susceptibility to cervical precancerous lesions in a Chinese population. Five polymorphisms in the 3′UTR of the CDK6 gene were evaluated in 164 cervical precancerous lesion cases and 296 control subjects. Differences in environmental factors between cases and controls were evaluated using the χ2 test or unpaired t-test. Logistic regression was used to examine the association between the five polymorphisms and cervical precancerous lesions. The model-free multifactor dimensionality reduction (MDR) method was performed to evaluate the interaction effect of environment variables and gene polymorphisms. Interactions on the additive scale are calculated by using the relative excess risk due to interaction (RERI). After controlling for potential confounders, a significantly decreased risk of cervical precancerous lesions for the GA genotype, rs8179, and the AT genotype, rs42033 [GA vs. GA: odds ratio (OR)adjusted=0.17, 95% confidence interval (CI), 0.05–0.57; AT vs. AA: ORadjusted=0.18, 95% CI, 0.05–0.59, respectively] was identified. Furthermore, following MDR analysis, a significant three-locus interaction model was identified, which involved the HPV infection, the number of pregnancies and rs8179. Additionally, a significant antagonistic interaction between the HPV infection and rs8179 was identified on an additive scale. Haplotype AGTA was associated with a decreased risk of developing cervical precancerous lesions (ORadjusted=0.21; 95% CI, 0.06–0.75). Thus, the present results indicated that the rs8179 and rs42033 polymorphisms confer genetic susceptibility to cervical precancerous lesions. Furthermore, the interaction between the rs8179 polymorphism in CDK6 and the HPV infection and haplotype AGTA may be associated with cervical precancerous lesions.

show abstract

Gene–asbestos interaction in malignant pleural mesothelioma susceptibility

Cited by 35 publications

References 28 publications

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population

Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Interactions between polymorphisms in the 3′untranslated region of the cyclin dependent kinase 6 gene and the human papillomavirus infection, and risk of cervical precancerous lesions

Contact Info

Product

Resources

About