Background

Numerous studies have sought associations between matrix metalloproteinase 9 (MMP-9) polymorphisms and breast cancer risk. However, these studies have yielded conflicting results. Hence, we performed an updated meta-analysis to clarify the effects of four MMP-9 gene polymorphisms (rs3918242, rs2250889, rs3787268, and rs17576) on breast cancer risk.

Methods

A comprehensive literature search for eligible studies was conducted in five electronic databases, including PubMed, Embase and Web of Science, up to March 1, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations in random-effects models. For the reduction of type I errors, a trial sequential analysis (TSA) was performed.

Results

Twenty-one studies (8813 breast cancer cases and 9323 controls) were included in the quantitative analysis. For rs3918242, the overall ORs were significant under allelic comparison (OR _{A vs. G} = 1.34; 95% CI 1.03, 1.74, P =0.028) and the recessive genetic model (OR _{AA vs. GG+GA} = 1.40; 95% CI 1.06, 1.84, P =0.016). For rs2250889, the ORs were significant under homozygote comparison (OR _{GG vs. CC} = 2.57; 95% CI 1.22, 5.42, P =0.013), heterozygote comparison (OR _{GC vs. CC} = 2.48; 95% CI 1.17, 5.23, P =0.018), and the dominant genetic model (OR _{GG+GC vs. CC} = 2.53; 95% CI 1.23, 5.20, P =0.012). No associations were observed for rs3787268 or rs17576. The subgroup analyses indicated that the risk effect of the rs3918242 A allele was observed only among Asians. TSA showed that the findings for rs3918242, rs3787268, and rs17576 were robust, but many more patients are needed before definitive conclusions can be made for rs2250889.

Conclusion

Our meta-analysis suggests that MMP-9 rs3918242, but not rs3787268 and rs17576 polymorphisms, may be risk factors for breast cancer. The effect of rs2250889 needs further confirmation with a larger sample size.

中文翻译：

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基质金属蛋白酶9多态性与乳腺癌风险之间的关联：最新的荟萃分析和试验序贯分析。

背景

大量研究已经寻求基质金属蛋白酶9（MMP-9）多态性与乳腺癌风险之间的关联。但是，这些研究产生了矛盾的结果。因此，我们进行了更新的荟萃分析，以阐明四种MMP-9基因多态性（rs3918242，rs2250889，rs3787268和rs17576）对乳腺癌风险的影响。

方法

截至2020年3月1日，在包括PubMed，Embase和Web of Science在内的五个电子数据库中对符合条件的研究进行了全面的文献检索。使用具有95％置信区间（CI）的汇总比值比（OR）评估强度随机效应模型中的关联。为了减少I型错误，进行了试验顺序分析（TSA）。

结果

二十一项研究（8813例乳腺癌病例和9323例对照）被纳入定量分析。对于rs3918242，在等位基因比较（OR _A对G = 1.34； 95％CI 1.03、1.74，P = 0.028）和隐性遗传模型（OR _{AA对GG + GA} = 1.40； 95％CI ）下，总体OR显着1.06、1.84，P = 0.016）。对于rs2250889，在纯合子比较（OR _GG与CC = 2.57; 95％CI 1.22，5.42，P = 0.013），杂合子比较（OR _GC与CC = 2.48; 95％CI 1.17，5.23，P ）下OR显着= 0.018）和显性遗传模型（或_{GG + GC与CC}= 2.53; 95％CI 1.23，5.20，P = 0.012）。rs3787268或rs17576未发现关联。亚组分析表明，仅在亚洲人中观察到rs3918242 A等位基因的风险影响。TSA显示rs3918242，rs3787268和rs17576的发现是可靠的，但是需要更多的患者才能对rs2250889做出明确的结论。

结论

我们的荟萃分析表明，MMP-9 rs3918242（而不是rs3787268和rs17576多态性）可能是乳腺癌的危险因素。rs2250889的效果需要以更大的样本量进一步确认。