A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer.
A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer.
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DOI：
10.1002/ijc.31530
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发表时间：
2018-09-15
影响因子：
6.4
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Tao Y;Sturgis EM;Huang Z;Sun Y;Dahlstrom KR;Wei Q;Li G
TGF-β 1 rs 1982073在miRNA-187结合位点的多态性可能改变TGF-β1的表达和功能，从而该多态性（基因型CT/CC）增加癌症易感性。HPV 16 L1血清阳性与口腔鳞状细胞癌（OSCC）的风险相关，包括口咽鳞状细胞癌（OPSCC）和口腔鳞状细胞癌（OCSCC）。因此，我们假设TGF-β 1 rs 1982073在miRNA-187结合位点的多态性结合HPV 16 L1血清阳性可能对OSCC易感性有联合作用。我们确定了325例口腔鳞癌患者和335例非西班牙裔白色人群中的无癌对照的TGF-β 1 rs 1982073基因型和HPV 16状态，并使用logistic回归模型评估对口腔鳞癌易感性的联合作用。TGF-β 1 rs 1982073多态性（CT/CC基因型）与HPV 16 L1血清学阳性通过联合作用增加OSCC的风险，尤其是在从不吸烟（OR，165.9; 95%CI，28.6-960.4）或从不饮酒（OR，196.0; 95%CI，28.2-1000.0）的OSCC受试者中。年轻受试者的OPSCC风险高于老年受试者（OR，23.5; 95% CI，6.3-87.0 vs. OR，6.0; 95% CI，1.7-17.9）。该多态性与HPV 16相关的口腔鳞癌和OPSCC之间也存在显著相关性。然而，OCSCC受试者没有类似的结果。我们的研究结果表明，TGF-β 1 rs 1982073和HPV 16 L1血清阳性的联合作用可增加HPV 16相关口腔癌的风险，特别是在不吸烟、不饮酒和年轻的OPSCC受试者中。这一结果可能有助于我们了解肿瘤发生过程并提高早期检测，这对预防和干预策略至关重要。然而，需要更大规模的研究来验证我们的发现。
TGF-β1rs1982073 polymorphism at the miRNA-187 binding site may alter TGF-β1 expression and function, and thereby this polymorphism (genotype CT/CC) increases cancer susceptibility. HPV16 L1 seropositivity is associated with the risk of oral squamous cell carcinoma (OSCC), including oropharyngeal squamous cell carcinoma (OPSCC) and oral cavity squamous cell carcinoma (OCSCC). Thus, we hypothesized that TGF-β1rs1982073 polymorphism at the miRNA-187 binding site combined with HPV16 L1 seropositivity may have a joint effect on OSCC susceptibility. We determined the genotypes of TGF-β1rs1982073 and HPV16 status in 325 OSCC subjects and 335 cancer-free controls in the non-Hispanic white population, and used logistic regression models to evaluate the joint effects on OSCC susceptibility. TGF-β1rs1982073 polymorphism (CT/CC genotype) combined with HPV16 L1 seropositivity increased the risk of OSCC via joint effects, particularly in OPSCC subjects who were never-smokers (OR, 165.9; 95% CI, 28.6–960.4) or never-drinkers (OR, 196.0; 95% CI, 28.2–1000.0), respectively. Younger subjects had a higher risk of OPSCC than older subjects (OR, 23.5; 95% CI, 6.3–87.0 vs. OR, 6.0; 95% CI, 1.7–17.9, respectively). The significant associations between this polymorphism and HPV16-associated OSCC and OPSCC were also observed. However, OCSCC subjects did not have similar results. Our findings suggest that the joint effects of TGF-β1rs1982073 and HPV16 L1 seropositivity can increase risk of HPV16-associated oral cancer, particularly in OPSCC subjects who are never-smokers, never-drinkers, and young. This result may help us understand the tumorigenesis process and improve early detection, which are critical for prevention and intervention strategies. However, larger studies are needed to validate our findings.
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影响因子：
6.2
作者：
Ji, Xuemei;Sturgis, Erich M.;Li, Guojun
通讯作者：
Li, Guojun
TGFβ 信号的背景
DOI：
10.1038/nrm3434
发表时间：
2012-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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影响因子：
6.6
作者：
Casanova-Salas, Irene;Rubio-Briones, Jose;Antonio Lopez-Guerrero, Jose
通讯作者：
Antonio Lopez-Guerrero, Jose
影响因子：
10.3
作者：
Chaturvedi, Anil K.;Madeleine, Margaret M.;Engels, Eric A.
通讯作者：
Engels, Eric A.
影响因子：
45.3
作者：
Chaturvedi, Anil K.;Engels, Eric A.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.