| 摘要: | 背景：在2022年，台灣的口腔癌在所有人癌症相關死亡率中排名第六，在男性癌症相關死亡中排名第四。吸菸、飲酒和咀嚼檳榔是口腔癌以及其他癌症和慢性疾病的重要危險因子。DNA甲基化是表觀遺傳修是最常見的形式，它可以居間調控環境和行為因素對基因表現的影響，而關於健康人群中危險因子與長散在核元 件1(long interspersed nuclear elements-1, LINE-1)甲基化程度之間關係的癌究相對較少。本研究的目的是闡明LINE-1甲基化程度與菸、酒和檳榔使用之間的相關性，並分析性別之間的差異。
方法：本研究採用橫斷性研究設計，納入台灣人體生物資料庫中2469名有DNA甲基化資料的參與者。生物資料庫中收集參與者的社會人口學變項、生活習慣與環境暴露等資料，並收集參與者血液及尿液提供體檢與生化檢驗資料。LINE-1甲基化程度以Illumina Infinium Methylation EPIC Bead Chip進行分析，以4個CpG位點的平均值表示。使用多變項迴歸分析吸菸、飲酒和咀嚼檳榔與LINE-1甲基化程度的相關性。
結果： 隨著年齡增加，LINE-1甲基化程度上升。在性別方面，女性的LINE-1甲基化程度顯著低於男性。此外，在父親籍貫方面，大陸各省分和閩南族群相比，LINE-1甲基化程較低(β=-0.10, 95%CI=-0.19 to -0.02, P=0.0204)。與從不使用香菸相比，曾經使用香菸組的LINE-1甲基化程度較高(β=0.23, 95%CI=0.13 to 0.32, P<0.0001)。曾經使用酒精組也比從不與用酒精組有較高的LINE-1甲基化程度(β=0.23, 95% CI=0.10 to 0.37, P=0.0008)。在男性的分析中，有使用檳榔習慣的人，其LINE-1甲基化程度顯著降低(β=-0.18, 95% CI=-0.35 to -0.01, P=0.0349)。進一步同時分析菸、酒和檳榔的使用狀況與LINE-1甲基化程度的關係。經過調整年齡、性別和父親籍貫後，發現與皆無不良習慣者相比，那組只有使用檳榔的人其LINE-1甲基化程度顯著地下降(β=-0.60, 95% CI=-1.13 to -0.07, P=0.0275)。
結論：研究結果顯示年齡、性別以及不良的生活習慣與LINE-1甲基化程度有關連性。而使用檳榔可能會降低男性的LINE-1甲基化程度。
Background: In 2022, oral cancer ranked sixth among all cancer-related deaths in Taiwan and fourth among male cancer-related deaths. Cigarette smoking, alcohol consumption, and betel nut chewing are important risk factors for oral cancer, as well as other cancers and chronic diseases. DNA methylation is the most common form of epigenetic modification, which can mediate the effects of environmental and behavioral factors on gene expression. There have been relatively few studies on the association between risk factors and LINE-1 methylation levels in healthy populations. This study aimed to investigate the association between LINE-1 methylation levels and the use of cigarette, alcohol and betel nut, and to analyze the differences between gender. Methods: This cross-sectional study, included 2469 participants with available DNA methylation data from Taiwan Biobank. The biobank collected participants’ sociodemographic characteristics, lifestyle habits, and environmental exposures, as well as physical examination, and biochemical test data. LINE-1 methylation levels were measured by Illumina Infinium MethylationEPIC Bead Chip, represented by the average of four CpG sites. The association between cigarette smoking, alcohol consumption, and betel nut chewing habits and the degree of LINE-1 methylation were analyzed by using multivariate regression.
Results: Older age is associated with higher LINE-1 methylation. Interms of gender, females exhibit significantly lower LINE-1 methylation levels than males. Furthermore, in terms of father’s native place, compared with the Minnan ethnic groups, the Chinese groups have lower LINE-1 methylation levels (β=-0.10, 95%CI=-0.19 to -0.02, P=0.0204). Compared with non-smokers, former smokers have higher LINE-1 methylation levels (β=0.23, 95%CI=0.13 to 0.32, P<0.0001). The group of former alcohol users also has higher LINE-1 methylation levels compared to those who never drank (β=0.23, 95% CI=0.10 to 0.37, P=0.0008). In a subgroup analysis of males, those with a habit of using betel nuts show a significant decrease in LINE-1 methylation levels (β=-0.18, 95% CI=-0.35 to -0.01, P=0.0349). The relationship between the use of cigarette, alcohol, and betel nut and methylation levels of LINE-1, was further analyzed simultaneously. After adjusting for age, gender, and father’s native place, it was found that compared with those without bad habits, the methylation level of LINE-1 in the group of people who only use betel nut was significantly decreased (β=-0.60, 95% CI= -1.13to -0.07, P=0.0275).
Conclusion: This study indicated that age, gender, and unhealthy lifestyle are associated with LINE-1 methylation levels. The use of betel nut may reduce LINE-1 methylation levels in men. |
