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Multicenter Study
. 2021 May;40(5):3305-3313.
doi: 10.1016/j.clnu.2020.10.057. Epub 2020 Nov 6.

Blunted PTH response to vitamin D insufficiency/deficiency and colorectal neoplasia risk

Jacklyn N Hellwege  1 , Xiangzhu Zhu  1 , Xiang Huang  1 , Martha J Shrubsole  1 , Lei Fan  2 , Bingshan Li  3 , Reid Ness  4 , Douglas L Seidner  4 , Edward L Giovannucci  5 , Todd L Edwards  1 , Qi Dai  6
Affiliations
Multicenter Study

Blunted PTH response to vitamin D insufficiency/deficiency and colorectal neoplasia risk

Jacklyn N Hellwege et al. Clin Nutr. 2021 May.

Abstract

Background & aims: In contrast to many observational studies, large-scale randomized trials do not support the protective role of vitamin D for the prevention of colorectal neoplasia. However, in previous studies, individuals with blunted parathyroid hormone (PTH) response to vitamin D insufficiency/deficiency (BPRVID), were not differentiated from those with high PTH response to vitamin D insufficiency/deficiency (HPRVID). Individuals with BPRVID are responsive to magnesium treatment, particularly treatment of magnesium plus vitamin D while those with HPRVID are responsive to vitamin D treatment. We prospectively compared these two distinct groups (i.e. BPRVID and HPRVID) for risk of incident adenoma, metachronous adenoma, and incident colorectal cancer (CRC) METHODS: Three nested case-control studies in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial.

Results: We found optimal 25(OH)D levels were associated with a significantly reduced risk of CRC, primarily among women. The associations between 25(OH)D and CRC risk significantly differed by PTH levels, particularly among women. Compared to individuals with optimal levels for both 25(OH)D and PTH, all others were at an elevated risk of incident CRC, primarily in women. We found those with BPRVID had 2.56-fold significantly increased risk of CRC compared to 1.65-fold non-significantly increased risk for those with HPRVID. Among women, we observed those with BPRVID had 4.79-6.25-fold significantly increased risks of incident CRC and adenoma whereas those with HPRVID had 3.65-fold significantly increased risk of CRC.

Conclusions: Individuals with BPRVID are at higher risks of incident adenoma and CRC compared to those with HPRVID, particularly among women.

Keywords: Colorectal neoplasia; Magnesium deficiency; Parathyroid hormone; Vitamin D.

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Figures

Figure 1.
Figure 1.
Relationship of Magnesium with 25(OH)D & PTH PTH: parathyroid hormone
Figure 2.
Figure 2.
Flow chart for three prospective nested case-control studies in PLCO Trial N: number; T0: baseline; T3/T5: at year 3 or 5; FSG: flexible sigmoidoscopy; CRC: colorectal cancer *241 controls shared by CRC and incident adenoma cases
See this image and copyright information in PMC

References

    1. McCullough ML, Zoltick ES, Weinstein SJ, Fedirko V, Wang M, Cook NR et al. Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts. J Natl Cancer Inst 2018. - PMC - PubMed
    1. Lee JE. Circulating levels of vitamin D, vitamin D receptor polymorphisms, and colorectal adenoma: a meta-analysis. Nutr Res Pract 2011;5:464–70. - PMC - PubMed
    1. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684–96. - PubMed
    1. Vaughan-Shaw PG, Zgaga L, Theodoratou E, Blackmur JP, Dunlop MG. Whether vitamin D supplementation protects against colorectal cancer risk remains an open question. Eur J Cancer 2019;115:1–3. - PubMed
    1. Haidari F, Abiri B, Iravani M, Razavi SM, Vafa M. The Effects of UVB and Vitamin D on Decreasing Risk of Colorectal Cancer Incidence and Mortality: A Review of the Epidemiology, Clinical Trials, and Mechanisms. Nutr Cancer 2019;71:709–17. - PubMed

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