He Qiangqiang, Wei Yaping, Zhu Hehao, Liang Qiongyue, Chen Ping, Li Shuqun, Song Yun, Liu Lishun, Wang Binyan, Xu Xiping, Dong Yuhan
Shenzhen International Graduate School, Tsinghua University, University Town of Shenzhen, No. 2279, Lishui Road. Nanshan District, Shenzhen, 518055, Guangdong, China.
Shenzhen Evergreen Medical Institute, Shenzhen, 518057, Guangdong, China.
Discov Oncol. 2024 Apr 2;15(1):97. doi: 10.1007/s12672-024-00960-y.
The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case-control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS).
We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer.
The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups.
These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer.
亚甲基四氢叶酸还原酶（MTHFR）在引导叶酸参与核苷酸合成或DNA甲基化过程中起着关键作用。MTHFR基因多态性C677T和A1298C与癌症易感性有关，但支持这种关联的证据并不明确。为了研究中国高血压人群中MTHFR C677T、A1298C与消化系统癌症之间的个体及联合关联，我们开展了一项基于人群的病例对照研究，纳入了751例消化系统癌症病例以及来自中国H型高血压注册研究（CHHRS）的一对一匹配对照。
我们使用条件逻辑回归模型评估消化系统癌症的多变量比值比（OR）和95%置信区间（CI）。
分析显示，与677CC基因型个体相比，CT基因型个体（调整后的OR：0.71；95%CI 0.52，0.97；P = 0.034）和TT基因型个体（调整后的OR：0.57；95%CI 0.40，0.82；P = 0.003；趋势P = 0.003）患消化系统癌症的风险显著降低。虽然A1298C与消化系统癌症风险未显示出可测量的关联，但按A1298C纯合子（AA）和杂合子（AC）对677CT基因型携带者进行进一步分层后，在这些亚组中发现了明显的趋势。
这些发现表明MTHFR C677T的T等位基因对消化系统癌症具有潜在的保护作用。此外，我们观察到MTHFR基因多态性的不同组合可能导致对消化系统癌症的易感性不同。
