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Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

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Abstract

Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms might influence the cancer risk due to their antiproliferative, antiangiogenic, and apoptotic effects. The aim of this study was to explore the genetic association of VDR polymorphisms with lung cancer risk in Tunisian population. The genotype and haplotype frequencies of four VDR polymorphisms, FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were studied using polymerase chain reaction and restriction fragment length polymorphism analysis in 240 patients with lung cancer and 280 healthy controls. The distribution of genotype frequencies differed significantly between lung cancer subjects and controls (FokI P adj  = 0.002; ApaI P adj  = 0.013). Haplotype analyses revealed a significant association between G-A-C and A-C-T haplotypes and lung cancer risk (P corr  = 0.0128, P corr  = 0.008). When patients were stratified according to gender, age, and smoking, significant associations were detected with FokI and TaqI polymorphisms. We found a lack of association between BsmI, TaqI polymorphisms and lung cancer risk (P > 0.05). Only, the attributable proportion due to interaction and the synergic index for interaction between ApaI polymorphism and smoking were statistically significant (P adj  = 0.74, 95 % CI = 0.38–1.20) and (P adj  = 0.63, 95 % CI = 0.05–1.21), respectively. Both the additive interaction measures suggested the existence of a biological interaction between SNP ApaI, but not FokI, and smoking. The multiplicative interaction measure was not statistically significant (P > 0.05). This is the first study in Tunisia, which suggested that VDR FokI and ApaI polymorphisms might be risk factors for lung cancer development.

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Acknowledgments

The authors thank all the and patients who participated in this study. The Tunisian ministry of high education and research supported this work. Many thanks to Professor Agnes Hamzaoui, head of Unit Research. UR/12-SP-15, Homeostasis and Cell Dysfunction. A. Mami Hospital of Pneumology, Ariana. Tunisia.

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Authors and Affiliations

  1. Department of Basic Sciences, Medicine School of Tunis, Tunis El Manar University, Tunis, 1007, Tunisia

    Wajih Kaabachi, Safa Kaabachi, Ahlem Rafrafi, Amira ben Amor, Kalthoum Tizaoui, Faycal Haj sassi & Kamel Hamzaoui

  2. Homeostasis and Cell Dysfunction, Research Unit UR/12-SP-15, A. Mami Hospital of Pneumology, Ariana, Tunisia

    Wajih Kaabachi, Safa Kaabachi, Ahlem Rafrafi, Amira ben Amor, Kalthoum Tizaoui, Faycal Haj sassi & Kamel Hamzaoui

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  1. Wajih Kaabachi
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Correspondence to Wajih Kaabachi.

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Kaabachi, W., Kaabachi, S., Rafrafi, A. et al. Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population. Mol Biol Rep 41, 6545–6553 (2014). https://doi.org/10.1007/s11033-014-3538-2

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  • DOI: https://doi.org/10.1007/s11033-014-3538-2

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