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SMAD7 polymorphisms and colorectal cancer risk: a meta-analysis of case-control studies
Yongsheng Huang1, Wenting Wu2, Meng Nie1
1Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Abstract:
Mothers against decapentaplegic homolog 7 (SMAD7) inhibits the transforming growth factor-β (TGF-β) signaling pathway, which regulates carcinogenesis and cancer progression. A number of studies have reported that SMAD7 polymorphisms (rs4464148, rs4939827, and rs12953717) are associated with colorectal cancer (CRC) risk, but the results from these studies remain conflicting. To determine a more precise estimation of the relationship between SMAD7 and CRC, we undertook a large-scale meta-analysis of 63 studies, which included a total of 187,181 subjects (86,585 cases and 100,596 controls). The results of our meta-analysis revealed that the C allele of rs4464148 [CC vs. TT+TC, odds ratio (OR) =1.23, 95% confidence interval (CI): 1.14-1.33, P < 0.01], the T allele of rs4939827 [TT vs. CC+TC, odds ratio OR=1.15, 95%CI:1.07-1.22, P < 0.01] and the T allele of rs12953717 [TT vs. CC+TC, OR =1.22, 95%CI:1.16-1.29, P < 0.01] were all associated with the increased CRC risk. Subgroup analysis according to ethnicity showed rs4464148 and rs12953717 were associated with the risk of CRC in both Caucasians and Asians, whereas rs4939827 was a risk polymorphism for CRC specifically in Caucasians. In summary, this large-scale meta-analysis indicated that SMAD7 polymorphisms (rs4464148, rs4939827, and rs12953717) correlate with CRC.
Insights
Genetic variations in Mothers against decapentaplegic homolog 7 (SMAD7) are linked to colorectal cancer (CRC) risk. This meta-analysis confirms that specific SMAD7 polymorphisms increase CRC susceptibility in diverse populations.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Mothers against decapentaplegic homolog 7 (SMAD7) negatively regulates the transforming growth factor-β (TGF-β) pathway.
- TGF-β signaling is crucial in carcinogenesis and cancer progression.
- Previous studies suggest associations between SMAD7 polymorphisms and colorectal cancer (CRC) risk, but findings are inconsistent.
Purpose of the Study:
- To conduct a comprehensive meta-analysis to precisely evaluate the association between SMAD7 polymorphisms (rs4464148, rs4939827, rs12953717) and CRC risk.
- To clarify the conflicting results from individual studies.
Main Methods:
- A large-scale meta-analysis was performed.
- Data from 63 studies, including 187,181 participants (86,585 cases, 100,596 controls), were analyzed.
- Statistical analysis included calculation of odds ratios (OR) and 95% confidence intervals (CI).
Main Results:
- The C allele of rs4464148 was associated with increased CRC risk (OR=1.23, 95%CI: 1.14-1.33).
- The T allele of rs4939827 was associated with increased CRC risk (OR=1.15, 95%CI: 1.07-1.22).
- The T allele of rs12953717 was associated with increased CRC risk (OR=1.22, 95%CI: 1.16-1.29).
- Subgroup analysis indicated rs4464148 and rs12953717 are risk factors in both Caucasians and Asians.
- Rs4939827 showed a significant association with CRC risk specifically in Caucasians.
Conclusions:
- SMAD7 polymorphisms rs4464148, rs4939827, and rs12953717 are significantly associated with colorectal cancer risk.
- These genetic variations contribute to CRC susceptibility across different ethnic groups, with some population-specific effects.
