PDF(Pubmed)
Abstract：
BACKGROUND: Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis.
METHODS: The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests.
RESULTS: Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P\' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P\'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P\'< 0.05), while prostate cancer shows an implied reverse causal relationship(P\'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy.
CONCLUSIONS: PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.
METHODS: The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests.
RESULTS: Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P\' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P\'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P\'< 0.05), while prostate cancer shows an implied reverse causal relationship(P\'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy.
CONCLUSIONS: PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.
摘要：
背景：观察性研究调查了恶性贫血（PA）与癌症之间的关系。然而,除了胃癌,结果大多是矛盾的。这项研究的目的是通过双向双样本孟德尔随机（MR）分析来研究PA与癌症之间的潜在因果关系。
方法：欧洲样本FinnGen项目提供了PA和20种位点特异性癌症的遗传汇总数据。这种双向双样本MR设计主要使用逆方差加权（IVW）方法来评估PA与癌症风险之间的因果关系。进行Benjamini-Hochberg校正以减少由多次测试引起的偏差。
结果：我们的研究表明PA与胃癌之间存在因果关系，前列腺癌,睾丸癌和皮肤恶性黑色素瘤，前列腺癌或胃癌与PA之间存在反向因果关系(P<0.05)。在Benjamini-Hochberg校正测试之后,PA与胃癌或前列腺癌之间仍然存在因果关系（P'<0.05），而PA与睾丸癌和皮肤恶性黑色素瘤之间仅有隐含的因果关系(P>0.05)。胃癌与PA之间仍存在反向因果关系(P<0.05)。而前列腺癌显示出隐含的反向因果关系(P>0.05)。此外,MR-Egger和MR-PRESSO测试未显示明显的水平多效性。
结论：PA可能与睾丸癌遗传相关，前列腺癌,胃癌,皮肤恶性黑色素瘤.
方法：欧洲样本FinnGen项目提供了PA和20种位点特异性癌症的遗传汇总数据。这种双向双样本MR设计主要使用逆方差加权（IVW）方法来评估PA与癌症风险之间的因果关系。进行Benjamini-Hochberg校正以减少由多次测试引起的偏差。
结果：我们的研究表明PA与胃癌之间存在因果关系，前列腺癌,睾丸癌和皮肤恶性黑色素瘤，前列腺癌或胃癌与PA之间存在反向因果关系(P<0.05)。在Benjamini-Hochberg校正测试之后,PA与胃癌或前列腺癌之间仍然存在因果关系（P'<0.05），而PA与睾丸癌和皮肤恶性黑色素瘤之间仅有隐含的因果关系(P>0.05)。胃癌与PA之间仍存在反向因果关系(P<0.05)。而前列腺癌显示出隐含的反向因果关系(P>0.05)。此外,MR-Egger和MR-PRESSO测试未显示明显的水平多效性。
结论：PA可能与睾丸癌遗传相关，前列腺癌,胃癌,皮肤恶性黑色素瘤.
