与衰老相关的多态性与肺癌易感性的关联：在日本人群中的病例对照研究。
The Association of Aging-Related Polymorphisms with Susceptibility to Lung Cancer: A Case-Control Study in a Japanese Population.
机构信息
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
出版信息
Asian Pac J Cancer Prev. 2021 Apr 1;22(4):1279-1285. doi: 10.31557/APJCP.2021.22.4.1279.
BACKGROUND
Telomere length is associated with cancer as well as aging. Telomerase reverse transcriptase (TERT), telomere RNA component (TERC) and oligonucleotide/oligosaccharide-binding fold containing 1 (OBFC1) are known to be involved in telomere length regulation. The tumor suppressor p53 (TP53), which has been shown to interact with tumor protein p53-binding protein 1 (TP53BP1), is implicated in the response to telomere shortening and aging. Polymorphisms in the TP53 and TP53BP1 genes are associated with various types of cancer. The aim of this study is to evaluate the impact of aging-related polymorphisms on lung cancer risk.
MATERIALS AND METHODS
This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of TERT rs2736100, TERC rs1881984, OBFC1 rs11191865, TP53 rs1042522 and TP53BP1 rs560191 on the risk of lung cancer using a Taq-Man real-time PCR assay. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
None of the main effects of any of the telomere-related polymorphisms were related to the risk of lung cancer. Similarly, none of the interactive effects of any of the telomere-related polymorphisms with smoking were associated with lung cancer risk. The significant multiplicative interaction between TERT rs2736100 and TP53BP1 rs560191 was statistically significant (OR for interaction = 0.34, 95% CI = 0.14-0.84). The multiplicative interaction between OBFC1 rs11191865 and TP53BP1 rs560191 was also statistically significant (OR for interaction = 2.44, 95% CI = 1.02-5.87) but the OR for interaction was in the opposite direction.
CONCLUSIONS
Our findings indicate that TP53BP1 rs560191 may predispose to lung cancer risk depending on the genotypes of telomere-related polymorphisms. Additional studies are warranted to confirm the findings suggested in the present study.
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背景
端粒长度与癌症以及衰老有关。端粒酶逆转录酶（TERT）、端粒 RNA 成分（TERC）和寡核苷酸/寡糖结合折叠含 1 型（OBFC1）被认为参与端粒长度的调节。已知肿瘤抑制因子 p53（TP53）与肿瘤蛋白 p53 结合蛋白 1（TP53BP1）相互作用，参与对端粒缩短和衰老的反应。TP53 和 TP53BP1 基因的多态性与各种类型的癌症有关。本研究旨在评估与衰老相关的多态性对肺癌风险的影响。
材料和方法
本病例对照研究包括来自日本的 462 例肺癌病例和 379 例对照。我们使用 Taq-Man 实时 PCR 检测方法检测 TERT rs2736100、TERC rs1881984、OBFC1 rs11191865、TP53 rs1042522 和 TP53BP1 rs560191 对肺癌风险的影响。使用非条件逻辑回归评估调整后的比值比（OR）和 95%置信区间（CI）。
结果
任何端粒相关多态性的主要作用均与肺癌风险无关。同样，任何端粒相关多态性与吸烟的相互作用均与肺癌风险无关。TERT rs2736100 和 TP53BP1 rs560191 之间存在显著的乘法交互作用（交互作用的 OR = 0.34，95%CI = 0.14-0.84）。OBFC1 rs11191865 和 TP53BP1 rs560191 之间的乘法交互作用也具有统计学意义（交互作用的 OR = 2.44，95%CI = 1.02-5.87），但交互作用的 OR 方向相反。
结论
我们的研究结果表明，TP53BP1 rs560191 可能根据端粒相关多态性的基因型导致肺癌风险增加。需要进一步的研究来证实本研究中提出的发现。
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