Zhong Shanliang, Chen Zhiyuan, Yu Xinnian, Li Wenjing, Tang Jinhai, Zhao Jianhua
Center of Clinical Laboratory Science, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Baiziting 42, Nanjing, 210009, China.
Mol Biol Rep. 2014 Sep;41(9):5775-85. doi: 10.1007/s11033-014-3450-9. Epub 2014 Jun 29.
The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To derive a more precise estimation, we carried out not only an updated meta-analysis but also a combined analysis based on all the available studies estimating the association between MTHFR C677T and/or A1298C and breast cancer risk. With respect to C677T polymorphism, the results suggested that 677T allele was associated with significantly elevated breast cancer risk in overall analysis (T vs. C: OR 1.073, 95 % CI 1.028-1.120; TT vs. CC: OR 1.177, 95 % CI 1.072-1.293; TT vs. CC + CT: OR 1.175, 95 % CI 1.073-1.288); Stratifying by ethnicity, significantly increased risk was only found in East Asians (T vs. C: OR 1.150, 95 % CI 1.039-1.273; TT vs. CC: OR 1.441, 95 % CI 1.145-1.814; TT vs. CC + CT: OR 1.413, 95 % CI 1.148-1.739); When stratified by menopausal status, statistically significant association was found for postmenopausal women (CT + TT vs. CC: OR 1.092, 95 % CI 1.011-1.179). In regard to A1298C polymorphism, no significant associations were found between the polymorphism and breast cancer risk. With respect to MTHFR haplotypes, significantly elevated breast cancer risk was associated with 677T-1298C for overall result (OR 1.498, 95 % CI 1.143-1.962) and for Caucasians (OR 2.088, 95 % CI 1.277-3.416) when compared with 677C-1298A; Haplotype 677C-1298C might provide higher protection than 677C-1298A in East Asians (OR 0.840, 95 % CI 0.742-0.949). The combined genotypes for C677T and A1298C produced a significant OR for the 677TT/1298AC relative to 677CC/1298AA in overall population (OR 2.047, 95 % CI 1.275-3.288); When stratified by ethnicity, significant ORs were only found for East Asians (677CC/1298CC vs. 677CC/1298AA: OR 0.686, 95 % CI 0.478-0.985; 677TT/1298AC vs. 677CC/1298AA: OR 2.181, 95 % CI 1.179-4.035). The findings suggest that the MTHFR C677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer.
亚甲基四氢叶酸还原酶（MTHFR）基因多态性与乳腺癌风险之间的关联已得到广泛研究，但其结果相互矛盾，尚无定论。为获得更精确的估计，我们不仅进行了一项更新的荟萃分析，还基于所有可用研究进行了综合分析，以评估MTHFR C677T和/或A1298C与乳腺癌风险之间的关联。关于C677T多态性，结果表明，在总体分析中，677T等位基因与乳腺癌风险显著升高相关（T vs. C：比值比1.073，95%置信区间1.028 - 1.120；TT vs. CC：比值比1.177，95%置信区间1.072 - 1.293；TT vs. CC + CT：比值比1.175，95%置信区间1.073 - 1.288）；按种族分层，仅在东亚人群中发现风险显著增加（T vs. C：比值比1.150，95%置信区间1.039 - 1.273；TT vs. CC：比值比1.441，95%置信区间1.145 - 1.814；TT vs. CC + CT：比值比1.413，95%置信区间1.148 - 1.739）；按绝经状态分层时，绝经后女性存在统计学显著关联（CT + TT vs. CC：比值比1.092，95%置信区间1.011 - 1.179）。关于A1298C多态性，未发现该多态性与乳腺癌风险之间存在显著关联。关于MTHFR单倍型，与677C - 1298A相比，总体结果（比值比1.498，95%置信区间1.143 - 1.962）以及高加索人群（比值比2.088，95%置信区间1.277 - 3.416）中，677T - 1298C与乳腺癌风险显著升高相关；在东亚人群中，单倍型677C - 1298C可能比677C - 1298A提供更高的保护作用（比值比0.840，95%置信区间0.742 - 0.949）。C677T和A1298C的联合基因型在总体人群中，相对于677CC/1298AA，677TT/1298AC产生了显著的比值比（比值比2.047，95%置信区间1.275 - 3.288）；按种族分层时，仅在东亚人群中发现显著的比值比（677CC/1298CC vs. 677CC/1298AA：比值比0.686，95%置信区间0.478 - 0.985；677TT/1298AC vs. 677CC/1298AA：比值比2.181，95%置信区间1.179 - 4.035）。研究结果表明，MTHFR C677T多态性而非A1298C多态性，以及它们联合基因型或单倍型的某些变体可能与乳腺癌的发生有关。
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