Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development.
Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development.
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DOI：
10.1371/journal.pone.0064053
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Swiss Hepatitis C Cohort Study Group
中科院分区：
文献类型：
--
作者：
Lange CM;Miki D;Ochi H;Nischalke HD;Bojunga J;Bibert S;Morikawa K;Gouttenoire J;Cerny A;Dufour JF;Gorgievski-Hrisoho M;Heim MH;Malinverni R;Müllhaupt B;Negro F;Semela D;Kutalik Z;Müller T;Spengler U;Berg T;Chayama K;Moradpour D;Bochud PY;Hiroshima Liver Study Group;Swiss Hepatitis C Cohort Study Group
维生素D不足与各种癌症的发生有关，但因果关系仍然难以捉摸。因此，我们的目的是确定维生素D血清水平的遗传决定因素和发展丙型肝炎病毒（HCV）相关的肝细胞癌（HCC）的风险之间的关系。CYP 2 R1、GC和DHCR 7基因型是血清25-羟基维生素D（25[OH]D3）水平降低的决定因素，分别对1279例慢性丙型肝炎伴HCC患者和4325例非HCC患者进行了研究，以探讨其与HCV相关HCC发生风险之间的关系。CYP 2 R1（rs 1993116，rs 10741657），GC（rs 2282679）和DHCR 7（rs7944926，rs 12785878）基因型与25（OH）D3血清水平之间的相关性在慢性丙型肝炎患者中也很明显。发现与25（OH）D3血清水平降低相关的这些单核苷酸多态性（SNP）的相同基因型与HCV相关的HCC相关（CYP 2 R1的P= 0.07 [OR = 1.13，95%CI =0.99-1.28]， GC的P = 0.007 [OR = 1.56，95%CI =1.12-2.15]，DHCR 7的P= 0.003 [OR = 1.42，95%CI =1.13-1.78];风险基因型的OR）。 相反，这些遗传变异与肝纤维化进展率（每个SNP P>0.2）或聚乙二醇干扰素-α和利巴韦林标准治疗的结果（每个SNP P>0.2）之间没有观察到相关性，表明25（OH）D3血清水平的遗传决定因素对肝癌发生的特定影响。我们的数据表明，维生素D在预防HCV相关肝癌发生中的作用相对较弱，但功能相关。
Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3) serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657), GC (rs2282679), and DHCR7 (rs7944926, rs12785878) genotypes and 25(OH)D3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs) that are associated with reduced 25(OH)D3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99–1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12–2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13–1.78] for DHCR7; ORs for risk genotypes). In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP) or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP) was observed, suggesting a specific influence of the genetic determinants of 25(OH)D3 serum levels on hepatocarcinogenesis. Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.
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影响因子：
5.8
作者：
Campbell, F. C.;Xu, Haibo;El-Tanani, M.;Crowe, P.;Bingham, V.
通讯作者：
Bingham, V.
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影响因子：
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影响因子：
3.5
作者：
Ahn J;Yu K;Stolzenberg-Solomon R;Simon KC;McCullough ML;Gallicchio L;Jacobs EJ;Ascherio A;Helzlsouer K;Jacobs KB;Li Q;Weinstein SJ;Purdue M;Virtamo J;Horst R;Wheeler W;Chanock S;Hunter DJ;Hayes RB;Kraft P;Albanes D
通讯作者：
Albanes D
影响因子：
168.9
作者：
Wang, Thomas J.;Zhang, Feng;Richards, J. Brent;Kestenbaum, Bryan;van Meurs, Joyce B.;Berry, Diane;Kiel, Douglas P.;Streeten, Elizabeth A.;Ohlsson, Claes;Koller, Daniel L.;Peltonen, Leena;Cooper, Jason D.;O'Reilly, Paul F.;Houston, Denise K.;Glazer, Nicole L.;Vandenput, Liesbeth;Peacock, Munro;Shi, Julia;Rivadeneira, Fernando;McCarthy, Mark I.;Anneli, Pouta;de Boer, Ian H.;Mangino, Massimo;Kato, Bernet;Smyth, Deborah J.;Booth, Sarah L.;Jacques, Paul F.;Burke, Greg L.;Goodarzi, Mark;Cheung, Ching-Lung;Wolf, Myles;Rice, Kenneth;Goltzman, David;Hidiroglou, Nick;Ladouceur, Martin;Wareham, Nicholas J.;Hocking, Lynne J.;Hart, Deborah;Arden, Nigel K.;Cooper, Cyrus;Malik, Suneil;Fraser, William D.;Hartikainen, Anna-Liisa;Zhai, Guangju;Macdonald, Helen M.;Forouhi, Nita G.;Loos, Ruth J. F.;Reid, David M.;Hakim, Alan;Dennison, Elaine;Liu, Yongmei;Power, Chris;Stevens, Helen E.;Jaana, Laitinen;Vasan, Ramachandran S.;Soranzo, Nicole;Bojunga, Joerg;Psaty, Bruce M.;Lorentzon, Mattias;Foroud, Tatiana;Harris, Tamara B.;Hofman, Albert;Jonsson, John-Olov;Cauley, Jane A.;Uitterlinden, Andre G.;Gibson, Quince;Jarvelin, Marjo-Riitta;Karasik, David;Siscovick, David S.;Econs, Michael J.;Kritchevsky, Stephen B.;Florez, Jose C.;Todd, John A.;Dupuis, Josee;Hyppoenen, Elina;Spector, Timothy D.
通讯作者：
Spector, Timothy D.
影响因子：
13.5
作者：
Petta, Salvatore;Camma, Calogero;Craxi, Antonio
通讯作者：
Craxi, Antonio