Dataset Information

Circulating Vitamin D Levels and Risk of Colorectal Cancer in Women.

ABSTRACT: Observational data on the association between circulating 25(OH)D and colorectal cancer risk are limited in women. To determine whether prediagnostic levels of 25(OH)D were associated with risk of incident colorectal cancer in the Women's Health Study (WHS), we conducted a nested case-control study using 274 colorectal cases and 274 controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Conditional logistic regression was used to estimate the OR and 95% confidence interval (CI) for colorectal cancer by 25(OH)D quartiles. Mean plasma 25(OH)D was lower in cases versus controls (21.9 vs. 23.9 ng/mL, P = 0.01). In multivariable-adjusted logistic regression models, plasma 25(OH)D was significantly and inversely associated with odds of colorectal cancer (quartile 4 [Q4] vs. quartile 1 [Q1]: OR, 0.45; 95% CI, 0.25-0.81; Ptrend 0.02). In addition, we observed a somewhat lower risk of colorectal cancer-related mortality after adjustment for matching variables, randomization treatment and other risk factors (Q4:Q1 OR, 0.40; 95% CI, 0.17-0.97; Ptrend 0.05). In this cohort of healthy women, we found a significant inverse association between prediagnostic 25(OH)D levels and risk of incident colorectal cancer, and a borderline significant inverse association between prediagnostic 25(OH)D levels and colorectal cancer-related mortality. These results support a possible association between plasma 25(OH)D and risk of colorectal cancer in women.

SUBMITTER: Chandler PD

PROVIDER: S-EPMC4526335 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Circulating Vitamin D Levels and Risk of Colorectal Cancer in Women.

Chandler Paulette D PD Buring Julie E JE Manson JoAnn E JE Giovannucci Edward L EL Moorthy M V MV Zhang Shumin S Lee I-Min IM Lin Jennifer H JH

Cancer prevention research (Philadelphia, Pa.) 20150326 8

Observational data on the association between circulating 25(OH)D and colorectal cancer risk are limited in women. To determine whether prediagnostic levels of 25(OH)D were associated with risk of incident colorectal cancer in the Women's Health Study (WHS), we conducted a nested case-control study using 274 colorectal cases and 274 controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood ...[more]

PMID: 25813525

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Project description:BackgroundExperimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health.MethodsWe pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models.ResultsCompared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection.ConclusionsHigher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

Project description:BackgroundBilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.MethodsIn a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.ResultsThe associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).ConclusionsAdditional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.

Project description:BackgroundObservational studies indicated that circulating vitamin C (VitC) levels may be correlated with the risk of endometrial cancer (EC). However, the causal effects and direction between them were still unclear.MethodsIn this study, 11 single nucleotide polymorphisms (SNPs) robustly correlated with plasma VitC levels were extracted from the latest genome-wide association study (GWAS), containing 52,018 individuals. Genetic data of EC were obtained from the Endometrial Cancer Association Consortium (ECAC) (12,906 cases and 108,979 controls). An inverse-variance weighted method was utilized as the primary analysis of Mendelian randomization (MR), supplemented by the weighted median, MR Pleiotropy Residual Sum and Outlier test (MR-PRESSO), and MR-Egger methods. Additional sensitivity analyses excluding 3 SNPs with secondary phenotypes were conducted to rule out the possible pleiotropic effects. Potential impacts of several risk factors of EC, such as obesity, body mass index (BMI), hypertension, and diabetes on VitC levels, were assessed. We additionally evaluated the effects of VitC on LDL cholesterol levels, HDL cholesterol levels, and triglycerides levels to probe into the possible mediators in the VitC-EC pathway.ResultsGenetically predicted higher plasma VitC levels (per 1 SD increase, approximately 20 μmol/L) were causally associated with an increased risk of EC overall [odds ratio (OR) 1.374, 95% CI 1.128-1.674, p = 0.0016], supported by complementary sensitivity analyses. In the subgroup analyses, genetically predicted higher levels of VitC were associated with a tendency of increased risks of both endometrioid (OR SD 1.324, 95% CI 0.959-1.829, p = 0.0881) and non-endometrioid histology (OR SD 1.392, 95% CI 0.873-2.220, p = 0.1647) while without statistical significance. The association remained significant after the exclusion of the three pleiotropic SNPs (OR SD 1.394, 95% CI 1.090-1.784, p = 0.0082). The confounders and mediators were unlikely to affect the VitC-EC relationship. The causal effect of EC on VitC levels was not supported (OR 1.001, 95% CI 0.998-1.004, p = 0.4468).ConclusionsThis bi-directional MR study demonstrated a causal risk role of higher circulating VitC at physiological levels on an increased risk of EC, which was independent of confounders and mediators. Further studies are warranted to elucidate the possible mechanisms.

Project description:BackgroundCalcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis.MethodsCirculating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted.ResultsHigher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β -0.06, 95% CI -0.08 to -0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β -0.17, 95% CI -0.25 to -0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed.ConclusionsSerum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

Dataset Information

Circulating Vitamin D Levels and Risk of Colorectal Cancer in Women.

Publications

Circulating Vitamin D Levels and Risk of Colorectal Cancer in Women.

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