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Synergistic association of CYP1A1 polymorphisms with increased susceptibility to squamous cell lung cancer in north Indian smokers

Abstract

Objectives

Studies in different populations have shown that polymorphisms within the CYP1A1 gene play an important role in determining individual susceptibility to lung cancer. However, the data obtained so far have been contradictory within the same or different populations. Few studies have focused on the synergistic effect of CYP1A1 polymorphisms on the susceptibility to lung cancer overall and to different histological subtypes along with the impact of smoking.

Methods

A total of 704 individuals (353 lung cancer patients and 351 controls) were evaluated for CYP1A1 polymorphisms. CYP1A1 genotyping was done by means of PCR-RFLP.

Results

A CYP1A1 mutant genotype was found to be significantly associated with lung cancer (OR = 3.15; 95% CI = 1.75-5.71; p = 0.0001) and this risk was 4-fold higher in case of squamous cell carcinoma (SCC). The CYP1A1 m2 allelic variant was found to be strongly associated with the risk of SCC and adenocarcinoma. The combined “at risk” genotypes of the CYP1A1 m1 and m2 allelic variants were associated with lung cancer risk and this risk was higher in case of SCC (OR = 2.0; 95% CI = 1.97-3.81; p = 0.028). Furthermore, the lung cancer risk was associated with smoking, especially in heavy smokers carrying CYP1A1 variant genotypes. We also observed that heavy smokers with the mutant m1 genotype were at increased risk of SCC (OR = 5.4; 95% CI = 2.4-11.9; p<0.0001). Furthermore, when stratified for smoking dose and histology, the effect was compounded in heavy smokers and SCC (OR = 7.5; 95% CI = 1.8-30.9; p = 0.004).

Conclusions

Polymorphism in the CYP1A1 gene is an important risk modifier for lung cancer.

Int J Biol Markers 2016; 31(4): e402 - e412

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/jbm.5000221

Authors

Yashila Girdhar, Navneet Singh, Digambar Behera, Siddharth Sharma

Article History

Disclosures

Financial support: This work was supported by a grant from the Indian Council of Medical Research, New Delhi, India (grant No. 5/13/126/2011/NCD-III).
Conflict of interest: None declared.

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Authors

Affiliations

  • Department of Biotechnology, Thapar University, Patiala, Punjab - India
  • Department of Pulmonary Medicine, Post Graduate Institute of Education and Medical Research (PGIMER), Chandigarh - India

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