Single nucleotide polymorphisms of the Fas gene are associated with papillary thyroid cancer

Thyroid cancer is a common endocrine neoplasm. Despite its good prognosis, it can lead to significant mortality due to metastasis and recurrence. However, the factors involved in metastasis are not well studied. Therefore, we selected matrix metalloproteinases 2 (MMP2) and determined whether it has any role in thyroid cancer. We sequenced the exons of MMP2 in 211 samples including 16 multi-nodular goiters and 195 differentiated thyroid cancers. We identified four non-synonymous single nucleotide polymorphisms (SNPs) of the MMP2 gene in 3.06% (6/195) thyroid cancers. Of the 4 MMP2 SNPs, 3 (75%) concomitantly had BRAFV600E. Hence, we speculated that the MMP2 SNPs may likely cooperate with BRAFV600E in promoting tumor aggressiveness. Overexpression of two MMP2 SNPs (P38L and T458I) exhibited markedly enhanced gelatinase activity with an intact dimerization and induced strong cortactin foci formation in HEK293T cells. Stable expression of the two MMP2 SNPs in BRAFV600E positive BCPAP cells dramatically enhanced cell proliferation, colony formation, and focus formation. Analysis of the morphology of MMP2 SNP bearing BCPAPV600E cells exhibited highly invasive phenotypes characterized by a high rate of wound healing and enhanced cell invasion compared with parental BCPAPV600E cells bearing vector. We also determined that BCPAPV600E cells stably transfected with MMP2 SNPs were highly sensitive to the treatment of BRAF inhibitor, PLX4720. Our study demonstrates that MMP2 SNPs could cooperate with BRAFV600E to promote oncogenicity, migration, and invasiveness of PTC cells. These results suggest that a subset of papillary thyroid cancer with this genetic makeup can benefit from BRAF-mediated therapeutic interventions.

Download Full-text

Single nucleotide polymorphisms associated with papillary thyroid cancer

Endocrine Abstracts ◽

10.1530/endoabs.35.p1103 ◽

2014 ◽

Author(s):

Dorota Kula ◽

Kalemba Michal ◽

Handkiewicz-Junak Daria ◽

Puch Zbigniew ◽

Kowalska Malgorzata ◽

...

Keyword(s):

Thyroid Cancer ◽

Single Nucleotide Polymorphisms ◽

Papillary Thyroid Cancer ◽

Nucleotide Polymorphisms ◽

Papillary Thyroid ◽

Single Nucleotide

Download Full-text

Common genetic variants in metabolism and detoxification pathways and the risk of papillary thyroid cancer.

Endocrine Related Cancer ◽

10.1530/erc-11-0372 ◽

2012 ◽

Vol 19 (3) ◽

pp. 333-344 ◽

Cited By ~ 8

Author(s):

Briseis Aschebrook-Kilfoy ◽

Gila Neta ◽

Alina V Brenner ◽

Amy Hutchinson ◽

Ruth M Pfeiffer ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Metal Binding ◽

Gene Interaction ◽

Nucleotide Polymorphisms ◽

Papillary Thyroid ◽

Single Nucleotide ◽

Logistic Regression Models ◽

False Discovery ◽

Common Genetic Variants

Relationships are unclear between polymorphisms in genes involved in metabolism and detoxification of various chemicals and papillary thyroid cancer (PTC) risk as well as their potential modification by alcohol or tobacco intake. We evaluated associations between 1647 tagging single nucleotide polymorphisms (SNPs) in 132 candidate genes/regions involved in metabolism of exogenous and endogenous compounds (Phase I/II, oxidative stress, and metal binding pathways) and PTC risk in 344 PTC cases and 452 controls. For 15 selected regions and their respective SNPs, we also assessed interaction with alcohol and tobacco use. Logistic regression models were used to evaluate the main effect of SNPs (Ptrend) and interaction with alcohol/tobacco intake. Gene- and pathway-level associations and interactions (Pgene interaction) were evaluated by combining Ptrend values using the adaptive rank-truncated product method. While we found associations between PTC risk and nine SNPs (Ptrend≤0.01) and seven genes/regions (Pregion<0.05), none remained significant after correction for the false discovery rate. We found a significant interaction between UGT2B7 and NAT1 genes and alcohol intake (Pgene interaction=0.01 and 0.02 respectively) and between the CYP26B1 gene and tobacco intake (Pgene interaction=0.02). Our results are suggestive of interaction between the genetic polymorphisms in several detoxification genes and alcohol or tobacco intake on risk of PTC. Larger studies with improved exposure assessment should address potential modification of PTC risk by alcohol and tobacco intake to confirm or refute our findings.

Download Full-text

BAX gene (−248 G > A) polymorphism in a sample of patients diagnosed with thyroid cancer in the Federal District, Brazil

The International Journal of Biological Markers ◽

10.1177/17246008211057576 ◽

2021 ◽

pp. 172460082110575

Author(s):

Ligia C.A. Cardoso-Duarte ◽

Caroline F. Fratelli ◽

Alexandre S.R. Pereira ◽

Jéssica Nayane Gomes de Souza ◽

Renata de Souza Freitas ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Protective Factor ◽

Federal District ◽

Genotypic Difference ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Papillary Thyroid ◽

Genotype Frequencies ◽

Bax Gene

Introduction Papillary thyroid cancer corresponds to approximately 1% of all carcinomas; nevertheless, it is the most prevalent endocrine neoplasm in the world. Studies reveal that the BAX (−248 G > A) polymorphism may be associated with negative regulation of BAX gene transcription activity, causing a decrease in its protein expression. Objective The present study aimed to describe the genotype and allele frequencies of BAX single nucleotide polymorphisms (−248 G > A) (rs4645878) in the research patients, and to associate its presence with susceptibility to papillary thyroid cancer. Methods This case-control study was conducted with 30 patients with papillary thyroid cancer. For the evaluation of genetic polymorphisms, the polymerase chain reaction-restriction fragment length polymorphism technique was employed. Allele and genotype frequencies were estimated using the SPSS program, and significant associations were considered when p < 0.05. Results There was a significant genotypic difference between papillary thyroid cancer and the control group (p = 0.042). The GG genotype provided a protective factor for papillary thyroid cancer (p = 0.012, odds ratio (OR) = 0.313; confidence interval (CI) = 0.123–0.794). Likewise the G allele was a protective factor for papillary thyroid cancer (p = 0.009; OR = 0.360; CI = 0.163–0.793). The BAX gene polymorphism (−248 G > A) was associated with papillary thyroid cancer. Conclusion BAX (−248 G > A) GG genotype carriers, or at least one mutated allele, was associated with papillary thyroid cancer in the Brazilian population studied, and the G allele presence is considered a protective factor against papillary thyroid cancer occurrence.

Download Full-text