Recently, Oh et al. (1) published in a recent article in the Journal a systematic review and meta-analysis based on 14 studies to explore the association between BRCA1 and BRCA2 gene mutations and the risk of colorectal cancer. Their results demonstrated a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.02 to 1.51). When subgroup analysis was performed by BRCA type, the authors observed that BRCA1 mutation was associated with an increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85), but BRCA2 mutation was not associated with an increased risk of colorectal cancer (OR = 1.10, 95% CI = 0.77 to 1.58). We have read this paper with great interest and found two issues that should be considered.
First, colorectal cancer mainly consists of colon cancer and rectal cancer in terms of tumor site, and Oh and colleagues’ paper (1) focused on BRCA1 and BRCA2 gene mutations and colorectal cancer risk. Therefore, both colon cancer and rectal cancer should be included in this study. To the best of our knowledge, three published papers—Ford et al. (2), van Asperen et al. (3), and the Breast Cancer Linkage Consortium (4)—reported colon and rectal cancer incidence in BRCA1 or BRCA2 mutation carriers, but the incidence of rectal cancer was not included in the meta-analyses. Missing data may be a bias for the current findings.
Second, the type of control may be different among the included studies. For example, the control cases (n = 120) in Table 1 in Oh and colleagues’ paper (1) are the frequencies of BRCA1/2 mutations in Chen-Shtoyerman and colleagues’ original paper (5). However, the control cases (4.2%) in Table 1 in Oh and colleagues’ paper (1) are the colorectal cancer incidence of relatives of cases without BRCA1/2 mutations in Risch and colleagues’ original paper (6). The authors should perform subgroup analysis stratified further by control type.
Taken together, the results of the study by Oh et al. (1) should be interpreted with caution. We hope that this comment will contribute to more accurate elaboration and substantiation of their findings (1).
Funding
This study was supported by grants from the National Natural Science Foundation of China (No. U1404815) and Henan Province University Science and Technology Innovation Talent Projects (17HASTIT045).
Notes
The funders did not have a role in the preparation of the correspondence or decision to publish. All authors declare no conflict of interest.
References
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