Ericson Ulrika, Sonestedt Emily, Ivarsson Malin I L, Gullberg Bo, Carlson Joyce, Olsson Håkan, Wirfält Elisabet
Clinical Research Center, Malmö University Hospital, Malmö, Sweden.
Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1101-10. doi: 10.1158/1055-9965.EPI-08-0401. Epub 2009 Mar 31.
Single nucleotide polymorphisms (SNP) of the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) may modify associations between folate intake and breast cancer. We examined if the association between tertiles of dietary folate equivalents (DFE) and breast cancer was different in subgroups according to genotypes of the MTHFR 677 C>T (rs1801133) and 1298A>C (rs1801131) SNPs and if the polymorphisms per se were associated with breast cancer.
This nested case-control study included 544 incident cases with invasive breast cancer and 1,088 controls matched on age and blood sampling date from the population-based Malmö Diet and Cancer cohort. Genotyping of the MTHFR SNPs was done with PCR-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Odds ratios (OR) were obtained by unconditional logistic regression.
DFE was positively associated with breast cancer in MTHFR 677CT/TT-1298AA women (P for trend = 0.01) but inversely associated in compound heterozygous women (P for trend = 0.01). Interaction was observed between DFE and the 1298C allele (P = 0.03). The 677T allele was associated with increased breast cancer risk in women above 55 years [multivariate adjusted OR, 1.34; 95% confidence interval (95% CI), 1.01-1.76] and an interaction was observed between the T allele and age (P = 0.03). Homozygosis for the 1298C allele was associated with increased risk in women between 45 and 55 years (multivariate adjusted OR, 1.89; 95% CI, 1.09-3.29).
In conclusion, a positive association between DFE and breast cancer was observed in MTHFR 677CT/TT-1298AA women but an inverse association was observed in 677CT-1298AC women. The 677T allele was associated with higher breast cancer risk in women above 55 years of age.
叶酸代谢酶亚甲基四氢叶酸还原酶（MTHFR）的单核苷酸多态性（SNP）可能会改变叶酸摄入量与乳腺癌之间的关联。我们研究了根据MTHFR 677 C>T（rs1801133）和1298A>C（rs1801131）SNP的基因型，膳食叶酸当量（DFE）三分位数与乳腺癌之间的关联在亚组中是否存在差异，以及这些多态性本身是否与乳腺癌相关。
这项巢式病例对照研究纳入了544例浸润性乳腺癌新发病例和1088例对照，这些对照在年龄和采血日期上与基于人群的马尔默饮食与癌症队列相匹配。MTHFR SNPs的基因分型采用基于PCR的基质辅助激光解吸/电离飞行时间质谱法进行。通过无条件逻辑回归获得比值比（OR）。
在MTHFR 677CT/TT-1298AA女性中，DFE与乳腺癌呈正相关（趋势P = 0.01），而在复合杂合子女性中呈负相关（趋势P = 0.01）。观察到DFE与1298C等位基因之间存在相互作用（P = 0.03）。677T等位基因与55岁以上女性患乳腺癌风险增加相关[多变量调整OR，1.34；95%置信区间（95%CI），1.01-1.76]，并且观察到T等位基因与年龄之间存在相互作用（P = 0.03）。1298C等位基因纯合与45至55岁女性风险增加相关（多变量调整OR，1.89；95%CI，1.09-3.29）。
总之，在MTHFR 677CT/TT-1298AA女性中观察到DFE与乳腺癌呈正相关，而在677CT-1298AC女性中观察到负相关。677T等位基因与55岁以上女性患乳腺癌风险较高相关。
