IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas.
IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas.
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DOI：
10.1002/ijc.24623
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发表时间：
2009-12-01
影响因子：
6.4
通讯作者：
Gammon, Marilie D.
中科院分区：
文献类型：
--
作者：
Hoyo, Cathrine;Schildkraut, Joellen M.;Murphy, Susan K.;Chow, Wong-Ho;Vaughan, Thomas L.;Risch, Harvey;Marks, Jeffrey R.;Jirtle, Randy L.;Calingeart, Brian;Mayne, Susan;Fraumeni, Joseph, Jr.;Gammon, Marilie D.
甘露糖6磷酸/胰岛素样生长因子2受体（M6 P/IGF 2 R）编码的蛋白质在肿瘤抑制中起关键作用，部分通过调节强效促分裂剂胰岛素样生长因子-2（IGF 2）的生物利用度。我们检验了M6 P/IGF 2 R外显子6的c.901 C>G（Leu>瓦尔）和外显子34的c.5002 G>A（Gly>Arg）中常见的非同义遗传变异与食管癌和胃癌风险相关的假设。这项基于人群的研究的研究参与者包括197名对照和182名病例，其中包括105名食管贲门腺癌（EGA），57名非贲门胃腺癌和20名食管鳞状细胞癌（ES）。在白色男性中，EGA（OR= 1.9; 95%CI=1.0-3.6）和非贲门胃癌（OR=2.5; 95%CI =1.2-5.5）与携带至少一个c.901 C>G等位基因相关的优势比（OR）升高，但与ES无关。探索性亚组分析表明，EGA与该变异体之间的关联在非甾体类抗炎药（NSAID）的不规则或非使用者（OR=2.3; 95%CI=1.2-4.2）和吸烟者（OR=2.1; 95%CI=1.0-4.2）中更强。携带c.5002G>A基因型与EGA之间的关联不明显。这些结果表明，M6 P/IGF 2 R的非同义多态性可能有助于EGA和非贲门腺癌的风险。需要更大规模的研究来证实这些发现。
The mannose 6 phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a protein that plays a critical role in tumor suppression, in part by modulating bioavailability of a potent mitogen, insulin-like growth factor-2 (IGF2). We tested the hypothesis that the common non-synonymous genetic variants in M6P/IGF2R c.901C>G (Leu>Val) in exon 6 and c.5002G>A (Gly>Arg) in exon 34 are associated with risk of esophageal and gastric cancers. Study participants in this population-based study comprise 197 controls and 182 cases, including 105 with esophageal-gastric cardia adenocarcinoma (EGA), 57 with non-cardia gastric adenocarcinoma and 20 with esophageal squamous cell carcinoma (ES). Among white males, odds ratios (ORs) were elevated in relation to carrying at least one c.901C>G allele for EGA (OR= 1.9; 95%CI=1.0–3.6) and non-cardia gastric cancer (OR=2.5; 95%CI=1.2–5.5), but not ES. Exploratory subgroup analyses suggested that associations between EGA and this variant were stronger among irregular or non-users of non-steroidal anti-inflammatory drugs (NSAIDs) (OR=2.3; 95%CI=1.2–4.2) and cigarette smokers (OR=2.1; 95%CI=1.0–4.2). An association between carrying the c.5002G>A genotype and EGA was not evident. These findings suggest that non-synonymous polymorphisms in M6P/IGF2R may contribute to the risks of EGA and non-cardia adenocarcinomas. Larger studies are required to confirm these findings.
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