Association of vitamin D receptor and toll like receptor genetic variants and haplotypes with colon cancer risk: A case control study in Egypt

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• 作者：Ragaa A. Ramadan^a ; ^{ragaa.abdelkader@gmail.com} ; Lubna M. Desouky^b ; Mai Moaaz^c ; Mostafa A. Elnaggar^d ; Mohamed Selima^e ; Mohamed Samir^e ; Ebtesam Abdalla^b
• 关键词：Vitamin D receptor ; Toll like receptors ; Colon cancer ; Fok1 ; Cdx2 ; TL4
• 刊名：Meta Gene
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：11
• 期：Complete
• 页码：209-216
• 全文大小：350 K
• 卷排序：11

文摘

Variants of vitamin D receptor (VDR) and toll like receptors (TLR) have been investigated in relation to colon cancer (CC) susceptibility, however results were always inconsistent. Methods: We examined the association of CC risk with four variants VDR rs2228570 (FokI), VDR rs11568820 (Cdx2) and Asp299Gly (rs4986790) and Asp399Ile (rs4986791) in TLR4. rs11568820 was assessed by allele specific-multiplex polymerase chain reaction, while the other variants were examined by restriction fragment length polymorphism. We evaluated whether any of the associations differed by tumor location or criteria. Results: The A allele of rs11568820 was associated with decreased risk with adjusted OR = 0.523 (0.344–0.796), p = 0.002, while G allele in Asp299Gly and T allele in Thr399Ile were associated with > 3 fold increased risk of CC with OR = 3.430 (1.588–7.408), p = 0.002 and OR = 3.290 (1.628–6.648), p = 0.001 respectively. G allele of Asp299Gly was more strongly associated with distal tumors OR = 4.952 (2.171–11.29), p < 0.001 than proximal tumors OR = 2.401 (1.002–5.751), p = 0.043 with almost 2 fold rise in the OR. On the other hand rs11568820 A allele was more associated with proximal tumors OR = 0.574 (0.355–0.926), p = 0.022 than distal tumors OR = 0.400 (0.224–0.712), p = 0.001. Haplotype analysis showed that the VDR haplotype A-F was associated with decreased CC risk with adjusted OR = 0.483 (0.309-0.753), p = 0.001. While in TL4 varients, both haplotypes A-T and G-C were associated with increased CC risk with adjusted OR = 3.705 (1.706-8.046), p = 0.001 and 4.401 (1.690-9.663), p = 0.002 respectively.ConclusionsWe conclude significant association of VDR rs11568820 (Cdx2) and TLR4 variants with CC, although results should be confirmed in additional studies.