Department of Digestive System, Anqing Municipal Hospital, Anqing, China.
Department of Thoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2024 Jan 12;14:1260941. doi: 10.3389/fimmu.2023.1260941. eCollection 2023.
With the advancement in early diagnosis and treatment, the prognosis for individuals diagnosed with breast cancer (BC) has improved significantly. The prognosis of primary breast cancer (PBC) survivors can be significantly influenced by the occurrence of colorectal cancer (CRC) as a secondary primary cancer (SPC). The objective of this study is to explore the possible genetic association between PBC and CRC, aiming to lay a groundwork for the development of preventive strategies against SPC-CRC following BC surgery.
We employed a bidirectional two-sample Mendelian randomization (MR) approach to thoroughly examine genetic instrumental variables (IVs) derived from genome-wide association studies (GWAS) conducted on PBC and CRC. And applied inverse variance weighted (IVW) and multiple other MR methods (weighted median, simple median, MR-PRESSO and MR-RAPS) to evaluate the association between the two cancers (PBC and CRC) at genetic level. Furthermore, the robustness of the findings was further confirmed through the utilization of the genetic risk score (GRS) method in a secondary analysis.
Forward MR analysis, a total of 179 BC genetic IVs, 25 estrogen receptor-negative (ER-) genetic IVs and 135 ER-positive (ER+) genetic IVs were screened. Reverse MR analysis, 179 genetic IVs of CRC, 25 genetic IVs of colon cancer, 135 genetic IVs of rectal cancer, 25 genetic IVs of left colon cancer and 135 genetic IVs of right colon cancer were screened. IVW and other MR methods found no significant genetic association between PBC and CRC ( > 0.05). Subgroup analysis also showed that ER- BC and ER+ BC were not correlated with the occurrence of CRC ( > 0.05). The findings of the secondary analysis using GRS were consistent with those obtained from the primary analysis, thereby confirming the robustness and reliability of this study.
Our findings do not provide any evidence supporting the association between PBC and CRC at the genetic level. Further large-scale prospective studies are warranted to replicate our findings.
随着早期诊断和治疗的进步，乳腺癌（BC）患者的预后已显著改善。原发性乳腺癌（PBC）幸存者的预后可能会因结直肠癌（CRC）作为第二原发癌（SPC）而受到显著影响。本研究旨在探讨 PBC 和 CRC 之间可能存在的遗传关联，为 BC 手术后预防 SPC-CRC 策略的制定奠定基础。
我们采用双向两样本 Mendelian 随机化（MR）方法，全面研究了来自 PBC 和 CRC 全基因组关联研究（GWAS）的遗传工具变量（IVs）。并应用逆方差加权（IVW）和其他多种 MR 方法（加权中位数、简单中位数、MR-PRESSO 和 MR-RAPS）来评估两种癌症（PBC 和 CRC）之间的遗传关联。此外，还通过二次分析中的遗传风险评分（GRS）方法进一步确认了研究结果的稳健性。
正向 MR 分析中，共筛选出 179 个 BC 遗传 IVs、25 个雌激素受体阴性（ER-）遗传 IVs 和 135 个 ER 阳性（ER+）遗传 IVs。反向 MR 分析中，共筛选出 179 个 CRC 遗传 IVs、25 个结肠癌遗传 IVs、135 个直肠癌遗传 IVs、25 个左结肠癌遗传 IVs 和 135 个右结肠癌遗传 IVs。IVW 和其他 MR 方法均未发现 PBC 和 CRC 之间存在显著的遗传关联（>0.05）。亚组分析也表明 ER- BC 和 ER+ BC 与 CRC 的发生无相关性（>0.05）。使用 GRS 进行的二次分析结果与主要分析结果一致，从而证实了本研究的稳健性和可靠性。
本研究结果未提供任何遗传水平上 PBC 和 CRC 之间存在关联的证据。需要进行更大规模的前瞻性研究来复制我们的发现。
