To our knowledge, this is the first systematic review and meta-analysis of published observational studies assessing the association between MI and incident cancer. Our results showed that the estimated cancer incidence rate after MI was 9.5% and the relation between MI and cancer incidence was uncertain. The pooled ORs of increased overall cancer risk were only significant in female patients, but not in male patients. Although the OR of cancer risk in female patients reached statistical significance, the absolute increased risk was only 10% (OR=1.10; 95% CI=1.01–1.20, P=0.025) and the heterogeneity was high. In terms of cancer type, the increased cancer risk was only significant for lung cancer, but not for prostate cancer or breast cancer. In addition, sub-group analysis by follow-up time suggested the increased risk of incident cancer did not persist over 6 months after MI event.
Sharing risk factors are one of the important reasons for association between MI and cancer. These shared risk factors can contribute to both the cardiovascular and the malignant event, with the malignancy occurring later.21 As a result, chance is a possible explanation for the increased cancer incidence after MI, and the independent association between MI and cancer may have been overlooked. Besides, the shared risk factor ‘smoking’, a known lung cancer cause,22 may partially account for our observation that lung cancer risk was significantly increased after MI.
In addition, the time since MI diagnosis must be considered when investigating cancer incidence. It is necessary to do such estimates by time, as cancer usually develops and evolves over several years. If cancer incidence is observed shortly after the start of MI follow-up, MI would be less likely to be a causal factor, and occult cancers could have occurred before the cardiovascular event.21 In our analysis, we did a subgroup analysis by follow-up time and found an interesting phenomenon. The risk of cancer incidence was the highest in the first follow-up period (<6 months). With follow-up time increasing, the ORs decreased sharply and became nonsignificant. This suggested that the higher cancer risk shortly after MI may not be due to MI itself, but other confounding factors such as surveillance bias. Patients with MI had more frequent clinical encounters with more diagnostic tests, especially in the first several months after MI event, and this would increase the chance of early detection of cancer.13
Although the above-mentioned shared risk factors, occult cancers, and surveillance bias may explain the increased cancer incidence after MI, we couldn’t exclude the possibility that MI itself can cause a higher risk of long-term cancer development. A recent large cohort study presented that, after a median follow-up of 1,020 days, atherosclerotic cardiovascular disease (ASCVD) itself increased the risk of cancer incidence.23 On the other hand, a laboratory experimental study by Meijers et al24 just showed heart failure stimulates tumor growth by cardiac excreted circulating factors. MI belongs to ASCVD and can also lead to heart failure in some patients. Therefore, it is still possible that MI can have some effect on the long-term risk of cancer incidence. As Hasin et al21 summarized, malignancy may be caused by biological alterations or treatment modalities related to the cardiovascular diseases. In the future, the links between MI and new onset cancer remain to be established by more basic and clinical research.
There are several limitations in our study. First, the present number of studies on MI and incident cancer is limited, especially in the investigation of cancers types (three studies) and cancer incidence by time (two studies). Since only two available studies were included in the analysis of cancer risk by follow-up time, the results should be interpreted with caution. Second, our study is related to the observational nature of the studies included with all inherited biases of observational designs. Third, heart failure also has some links with cancer incidence, but most of the studies included did not supply data on heart failure or left ventricular ejection fraction. Therefore, heart failure could become a confounder. However, current evidence represented the best available and all studies included were of moderate-to-high quality, including population-based studies.
From available evidence, the increased overall cancer risk after MI was only significant in female but not in male patients. Besides, the increased cancer risk could be driven by increased short-term cancer incidence after MI, and certain cancer types, such as lung cancer. However, due to the limitations listed above, further studies with larger sample sizes and long-term follow-up are warranted to establish the association between MI and new onset cancer.
This work was supported by a National Natural Science Foundation of China grant (81803939) to Na Li.
The authors report no conflicts of interest in this work.
Zhigang Huang,1,* Yanda Zhang,1,* Haitao Sun,2 Jiamei Wang,1 Jian Zhao1
1Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; 2Department of Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*These authors contributed equally to this work
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Source:Cancer Management and Research.
Originally published March 1, 2019.