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Association study between genetic variations in Axin2 gene and lung cancer risk in North Indian population: A
Charu Bahl1, Siddharth Sharma1, Navneet Singh2
11 Department of Biotechnology, Thapar University, Patiala, India.
Abstract:
Wnt pathway has been implicated in the process of human carcinogenesis. Axis inhibition protein2 ( Axin2), a major scaffold protein is an antagonist of Wnt pathway and is potent to act as a tumor suppressor gene in various human cancers. Therefore, the seven polymorphic sites of Axin2 gene were analyzed, in relation to lung cancer susceptibility in North Indians. A total of 608 subjects were genotyped using PCR-RFLP technique for each polymorphic site including 303 cases and 305 controls. Further association analysis was carried out using logistic regression approach to obtain adjusted odds ratio and statistical significance. MDR and CART analysis were applied to evaluate high order interactions between the SNP's. Three out of seven studied polymorphic sites showed a strong protective effect in subjects having mutant genotype for Axin2 148 C >T and heterozygous genotype for 1365 G > A and 1712 + 19 G > T towards lung cancer risk. The other important finding was the significant association of Axin2 148 C >T in SQCC patients having variant (TT) genotype. Axin2 1712 + 19 G >T showed a decreased risk for all the histological subtypes in patients with heterozygous (GT) genotype. MDR analysis predicted a best interaction model ( Axin2 148, Axin2 2062 and Axin2 1712 +19) with maximum CVC (10/10) and minimum prediction error (0.38) along with significant permutation p-value. CART analysis gave a wide spectrum of interactive combinations which exhibited a major contribution in modulating lung cancer susceptibility. Axin2 148 and Axin2 1712 + 19 were found to play a major role in modulating lung cancer risk.
Insights
Genetic variations in the Axin2 gene, specifically at sites 148 C>T and 1712+19 G>T, show a protective effect against lung cancer in North Indians. These Axin2 polymorphisms influence lung cancer susceptibility and may act as tumor suppressors.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The Wnt signaling pathway is crucial in human carcinogenesis.
- Axis inhibition protein 2 (Axin2) antagonizes the Wnt pathway and functions as a tumor suppressor.
- Genetic variations in Axin2 may influence lung cancer susceptibility.
Purpose of the Study:
- To investigate the association between seven polymorphic sites in the Axin2 gene and lung cancer risk in a North Indian population.
- To identify specific Axin2 variants that confer protection or increase susceptibility to lung cancer.
Main Methods:
- Genotyping of 608 subjects (303 cases, 305 controls) for seven Axin2 polymorphic sites using PCR-RFLP.
- Association analysis using logistic regression to determine odds ratios and statistical significance.
- Multivariate analysis including MDR and CART to evaluate gene-gene interactions.
Main Results:
- Three Axin2 polymorphic sites (148 C>T, 1365 G>A, 1712+19 G>T) demonstrated a protective effect against lung cancer.
- The Axin2 148 C>T variant (TT genotype) was significantly associated with squamous cell carcinoma (SQCC).
- Axin2 1712+19 G>T heterozygous genotype (GT) showed decreased risk across all histological subtypes.
- MDR and CART analyses identified significant interactions between Axin2 148, 2062, and 1712+19 SNPs in modulating lung cancer risk.
Conclusions:
- Specific Axin2 gene polymorphisms (148 C>T, 1365 G>A, 1712+19 G>T) are associated with altered lung cancer risk in North Indians.
- Axin2 variants, particularly 148 and 1712+19, play a significant role in modulating lung cancer susceptibility.
- These findings highlight the potential of Axin2 as a biomarker for lung cancer risk assessment.
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