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钙摄入量及钙敏感受体基因变异与结直肠癌死亡率的关系:一项对18952例患者的国际合作研究

Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients.

作者信息

Wesselink Evertine, Gauderman William, Berndt Sonja I, Brenner Hermann, Buchanan Daniel D, Campbell Peter T, Chan Andrew T, Chang-Claude Jenny, Cotterchoi Michelle, Gunter Marc J, Hoffmeister Michael, Joshi Amit D, Newton Christina C, Pai Rish K, Pellatt Andrew J, Phipps Amanda I, Song Mingyang, Um Caroline Y, van Guelpen Bethany, White Emily, Peters Ulrike, van Duijnhoven Fränzel J B

机构信息

Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.

Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA USA.

出版信息

BJC Rep. 2024;2(1):63. doi: 10.1038/s44276-024-00077-3. Epub 2024 Sep 2.

Abstract

BACKGROUND

Research on calcium intake as well as variants in the calcium sensor receptor ( gene and their interaction in relation to CRC survival is still limited.

METHODS

Data from 18,952 CRC patients, were included. Associations between primarily pre-diagnostic dietary ( = 13.085), supplemental ( = 11,837), total calcium intake ( = 5970) as well as 325 single nucleotide polymorphisms (SNPs) of the gene ( = 15,734) in relation to CRC-specific and all-cause mortality were assessed using Cox proportional hazard models. Also interactions between calcium intake and variants in the gene were assessed.

RESULTS

During a median follow-up of 4.8 years (IQR 2.4-8.4), 6801 deaths occurred, of which 4194 related to CRC. For all-cause mortality, no associations were observed for the highest compared to the lowest sex- and study-specific quartile of dietary (HR 1.00, 95%CI 0.92-1.09), supplemental (HR 0.97, 95%CI 0.89-1.06) and total calcium intake (HR 0.99, 95%CI 0.88-1.11). No associations with CRC-specific mortality were observed either. Interactions were observed between supplemental calcium intake and several SNPs of the gene.

CONCLUSION

Calcium intake was not associated with all-cause or CRC-specific mortality in CRC patients. The association between supplemental calcium intake and all-cause and CRC-specific mortality may be modified by genetic variants in the gene.

摘要

背景

关于钙摄入量以及钙敏感受体(基因)变体及其与结直肠癌生存的相互作用的研究仍然有限。

方法

纳入了18952例结直肠癌患者的数据。使用Cox比例风险模型评估主要诊断前饮食(n = 13085)、补充剂(n = 11837)、总钙摄入量(n = 5970)以及该基因的325个单核苷酸多态性(SNP,n = 15734)与结直肠癌特异性死亡率和全因死亡率之间的关联。还评估了钙摄入量与该基因变体之间的相互作用。

结果

在中位随访4.8年(四分位间距2.4 - 8.4年)期间,发生了6801例死亡,其中4194例与结直肠癌相关。对于全因死亡率,与性别和研究特异性最低四分位数相比,最高四分位数的饮食(风险比1.00,95%置信区间0.92 - 1.09)、补充剂(风险比0.97,95%置信区间0.89 - 1.06)和总钙摄入量(风险比0.99,95%置信区间0.88 - 1.11)均未观察到关联。也未观察到与结直肠癌特异性死亡率的关联。在补充钙摄入量与该基因的几个SNP之间观察到了相互作用。

结论

钙摄入量与结直肠癌患者的全因死亡率或结直肠癌特异性死亡率无关。补充钙摄入量与全因死亡率和结直肠癌特异性死亡率之间的关联可能会被该基因的遗传变体所改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f46/11523989/8b758a1ae869/44276_2024_77_Fig1_HTML.jpg

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