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The DBP Phenotype Gc-1f/Gc-1f Is Associated with Reduced Risk of Cancer. The Tromso Study.

ABSTRACT: In addition to its role as a transport protein, the vitamin D binding protein (DBP) may also affect lipid metabolism, inflammation and carcinogenesis. There are three common variants of the DBP, Gc1s (1s), Gc1f (1f), Gc2 (2) that result in six common phenotypes (1s/1s, 1s/1f, 1s/2, 1f/1f, 1f/2, and 2/2). These phenotypes can be identified by genotyping for the two single nucleotide polymorphisms rs7041 and rs4588 in the GC gene. The DBP variants have different binding coefficients for the vitamin D metabolites, and accordingly there may be important relations between DBP phenotypes and health.DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2010- 2013. Genotyping was performed for rs7041 and rs4588 and serum 25-hydroxyvitamin D (25(OH)D) was measured.Genotyping for rs7041 and rs4588 was performed successfully in 11 704 subjects. Among these, 1660 were registered with incident MI, 958 with T2DM, 2410 with cancer and 4318 had died. Subjects with the DBP phenotype 1f/1f had 23 - 26 % reduced risk of incident cancer compared to the 1s/1s and 2/2 phenotypes (P < 0.02, Cox regression with gender as covariate). Differences in serum 25(OH)D levels could not explain the apparent cancer protective effect of the DBP variant 1f. In addition to cancer and 25(OH)D, there were significant associations between DBP phenotype and body height, hip circumference and serum calcium.There are important biological differences between the common DBP phenotypes. If the relation between the DBP variant 1f and cancer is confirmed in other studies, determination of DBP phenotype may have clinical importance.

SUBMITTER: Jorde R

PROVIDER: S-EPMC4436319 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The DBP Phenotype Gc-1f/Gc-1f Is Associated with Reduced Risk of Cancer. The Tromsø Study.

Jorde Rolf R Schirmer Henrik H Wilsgaard Tom T Bøgeberg Mathiesen Ellisiv E Njølstad Inger I Løchen Maja-Lisa ML Joakimsen Ragnar Martin RM Grimnes Guri G

PloS one 20150518 5

<h4>Background and objective</h4>In addition to its role as a transport protein, the vitamin D binding protein (DBP) may also affect lipid metabolism, inflammation and carcinogenesis. There are three common variants of the DBP, Gc1s (1s), Gc1f (1f), Gc2 (2) that result in six common phenotypes (1s/1s, 1s/1f, 1s/2, 1f/1f, 1f/2, and 2/2). These phenotypes can be identified by genotyping for the two single nucleotide polymorphisms rs7041 and rs4588 in the GC gene. The DBP variants have different bi ...[more]

PMID: 25993554

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Project description:BackgroundElevated platelet count is associated with risk of venous thromboembolism in cancer patients initiating chemotherapy. It is not known whether this risk by platelet count is causal or merely reflects the malignant disease. We investigated whether pre-cancer platelet count alone or together with high leukocyte count was associated with risk of venous thromboembolism in subjects who did and did not develop cancer during follow-up in a population-based cohort study.MethodsPlatelet count and other baseline characteristics were measured in 25160 initially cancer-free subjects who participated in the Tromsø Study in 1994-1995. Incident cancer and symptomatic venous thromboembolism events were registered up to December 31st, 2009. Multivariable Cox regression models were used to calculate hazard ratio for venous thromboembolism across categories of platelet count (<40th, 40-80th, and >80th percentile) with 95% confidence interval.ResultsDuring follow-up, 2082 subjects were diagnosed with cancer. Platelet count was measured on average 8.3 years before the cancer diagnosis. There were 129 venous thromboembolism events in the cancer cohort (13.5 per 1000 person-years) and 377 in the non-cancer cohort (1.2 per 1000 person-years). In cancer patients, pre-cancer platelet count above the 80th percentile (?295×10(9)/L) was associated with a 2-fold higher risk of venous thromboembolism (Hazard ratio: 1.98, 95% confidence interval 1.21-3.23) compared to platelet count below the 40th percentile (<235×10(9)/L). Concomitant high platelet and leukocyte counts showed a synergistic effect on the VTE risk. In cancer-free subjects, no association was found.CommentIn conclusion, pre-cancer platelet count was associated with risk of symptomatic venous thromboembolism in cancer patients, but not in cancer-free subjects. Our findings suggest that platelet count and platelet-leukocyte interactions may play a role in the pathogenesis of cancer-related venous thromboembolism.

Dataset Information

The DBP Phenotype Gc-1f/Gc-1f Is Associated with Reduced Risk of Cancer. The Tromso Study.

Publications

The DBP Phenotype Gc-1f/Gc-1f Is Associated with Reduced Risk of Cancer. The Tromsø Study.

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