与一碳代谢相关的基因多态性与乳腺癌风险的关联受饮食的影响，当遵循地中海饮食模式的程度较低时，这种关联更高。
Associations of one-carbon metabolism-related gene polymorphisms with breast cancer risk are modulated by diet, being higher when adherence to the Mediterranean dietary pattern is low.
机构信息
Department of Epidemiology and Health Statistics, Southeast University, , Dingjiaqiao Road 87th, Nanjing 210009, Jiangsu, Nanjing, China.
Department of Chronic Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.
出版信息
Breast Cancer Res Treat. 2021 Jun;187(3):793-804. doi: 10.1007/s10549-021-06108-8. Epub 2021 Feb 18.
PURPOSE
Breast cancer is more likely attributed to a combination of genetic variations and lifestyle factors. Both one-carbon metabolism and diet-related factors could interfere with the carcinogenesis of breast cancer (BC), but whether diet consumed underlie a specific metabolism pathway could influence the impact of genetic variants on breast cancer risk remains equivocal.
METHODS
A case-control study of the Chinese female population (818 cases, 935 controls). 13 SNPs in eight one-carbon metabolism-related genes (MTHFD1, TYMS, MTRR, MAT2B, CDO1, FOLR1, UNG2, ADA) were performed. Diet was assessed by a validated food-frequency questionnaire. We examined the associations of the adherence to the Mediterranean dietary pattern (MDP) and single-nucleotide polymorphisms (SNPs) of one-carbon metabolism with breast cancer risk. We constructed an aggregate polygenic risk score (PRS) to test the additive effects of genetic variants and analyzed the gene-diet interactions.
RESULTS
High adherence (highest quartile) to the MDP decreased the risk of breast cancer among post- but not premenopausal women, respectively (OR = 0.54, 95% CI = 0.38 to 0.78 and 0.90, 0.53 to 1.53). Neither of the polymorphisms or haplotypes was associated with breast cancer risk, irrespective of menopause. However, a high PRS (highest quartile) was associated with more than a doubling risk in both post- and premenopausal women, respectively (OR = 1.95, 95% CI = 1.32 to 2.87 and 2.09, 1.54 to 2.85). We found a gene-diet interaction with adherence to the MDP for aggregate PRS (P-interaction = 0.000) among postmenopausal women. When adherence to the MDP was low (< median), carries with high PRS (highest quartile) had higher BC risk (OR = 2.80, 95% CI = 1.55 to 5.07) than low PRS (lowest quartile), while adherence to the MDP was high (≥ median), the association disappeared (OR = 1.57, 95% CI = 0.92 to 2.66).
CONCLUSION
High adherence to the MDP may counteract the genetic predisposition associated with one-carbon metabolism on breast cancer risk in postmenopausal women.
目的
乳腺癌更可能归因于遗传变异和生活方式因素的共同作用。一碳代谢和饮食相关因素都可能干扰乳腺癌（BC）的发生，但饮食是否遵循特定的代谢途径会影响遗传变异对乳腺癌风险的影响仍存在争议。
方法
采用中国女性人群的病例对照研究（818 例病例，935 例对照）。对 8 个一碳代谢相关基因（MTHFD1、TYMS、MTRR、MAT2B、CDO1、FOLR1、UNG2、ADA）中的 13 个单核苷酸多态性（SNP）进行了检测。通过验证过的食物频率问卷评估饮食情况。我们研究了地中海饮食模式（MDP）的依从性和一碳代谢单核苷酸多态性（SNP）与乳腺癌风险之间的关系。我们构建了一个综合多基因风险评分（PRS）来检验遗传变异的累加效应，并分析了基因-饮食的相互作用。
结果
高（最高四分位数）MDP 依从性降低了绝经后女性乳腺癌的发病风险（OR=0.54，95%CI=0.38 至 0.78 和 0.90，0.53 至 1.53），但在绝经前女性中无此作用。无论绝经状态如何，多态性或单倍型均与乳腺癌风险无关。然而，高 PRS（最高四分位数）在绝经后和绝经前女性中分别使风险增加一倍以上（OR=1.95，95%CI=1.32 至 2.87 和 2.09，1.54 至 2.85）。我们发现，绝经后妇女的综合 PRS 与 MDP 依从性之间存在基因-饮食相互作用（P 交互=0.000）。当 MDP 依从性较低（<中位数）时，携带高 PRS（最高四分位数）的患者患乳腺癌的风险更高（OR=2.80，95%CI=1.55 至 5.07），而 MDP 依从性较高（≥中位数）时，这种关联消失（OR=1.57，95%CI=0.92 至 2.66）。
结论
绝经后妇女中，高 MDP 依从性可能会抵消与一碳代谢相关的遗传易感性与乳腺癌风险之间的关联。
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