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Association study between genetic variations in Axin2 gene and lung cancer risk in North Indian population: A multiple interaction analysis.

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.
PMID
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Authors

Mayor MeshTerms

Polymorphism, Single Nucleotide

Keywords

Axin2

Lung cancer

Wnt pathway

single-nucleotide polymorphism

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28378643
OWN - NLM
STAT- MEDLINE
DA  - 20170405
DCOM- 20170410
LR  - 20170410
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 4
DP  - 2017 Apr
TI  - Association study between genetic variations in Axin2 gene and lung cancer risk
      in North Indian population: A multiple interaction analysis.
PG  - 1010428317695533
LID - 10.1177/1010428317695533 [doi]
AB  - 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.
FAU - Bahl, Charu
AU  - Bahl C
AD  - 1 Department of Biotechnology, Thapar University, Patiala, India.
FAU - Sharma, Siddharth
AU  - Sharma S
AD  - 1 Department of Biotechnology, Thapar University, Patiala, India.
FAU - Singh, Navneet
AU  - Singh N
AD  - 2 Department of Pulmonary Medicine, Post Graduate Institute of Education and
      Medical Research (PGIMER), Chandigarh, India.
FAU - Behera, Digamber
AU  - Behera D
AD  - 2 Department of Pulmonary Medicine, Post Graduate Institute of Education and
      Medical Research (PGIMER), Chandigarh, India.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (AXIN2 protein, human)
RN  - 0 (Axin Protein)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Axin Protein/*genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - India
MH  - Lung Neoplasms/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Risk
OTO - NOTNLM
OT  - Axin2
OT  - Lung cancer
OT  - Wnt pathway
OT  - single-nucleotide polymorphism
EDAT- 2017/04/06 06:00
MHDA- 2017/04/11 06:00
CRDT- 2017/04/06 06:00
AID - 10.1177/1010428317695533 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Apr;39(4):1010428317695533. doi: 10.1177/1010428317695533.

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