Dietary Intake of Lutein and Diabetic Retinopathy in the Atherosclerosis Risk in Communities Study (ARIC)

<p><i><b>Purpose</b></i>: We tested the hypothesis that dietary intake of lutein is inversely associated with prevalence of diabetic retinopathy (DR) due to its antioxidant and anti-inflammatory properties and location within the retina.</p> <p><i><b>Methods</b></i>: We used logistic regression to examine the association between prevalent DR and energy-adjusted lutein intake by quartile (Q) using data collected from 1430 Atherosclerosis Risk in Communities Study (ARIC) participants with diabetes (<i>n</i> = 994 white, <i>n</i> = 508 black). DR was assessed from 45° non-mydriatic retinal photographs of one randomly chosen eye taken at visit 3 (1993–1995). Dietary lutein intake was estimated using a 66-item food frequency questionnaire at visit 1 (1987–1989).</p> <p><i><b>Results</b></i>: Median estimated daily lutein intake was 1370 µg/1000 kcals and prevalence of DR was ~21%. We found a crude association between lutein and DR (odds ratio, OR, 2.11, 95% confidence interval, CI, 1.45–3.09 for Q4, high intake, vs. Q1, low intake; <i>p</i> for trend <0.0001), which was attenuated after adjustment for ethnicity, duration of diabetes, glycosylated hemoglobin levels, field center and energy intake (OR 1.41, 95% CI 0.87–2.28; <i>p</i> for trend = 0.01). In analyses limited to persons with short diabetes duration (<6 years), the association no longer persisted (OR 0.94, 95% CI 0.31–2.16; <i>p</i> for trend =0.72) compared to the association in those with longer diabetes duration (≥6 years; OR 1.58, 95% CI 0.91–2.75; <i>p</i> for trend = 0.01).</p> <p><i><b>Conclusion</b></i>: Contrary to our hypothesis, we found that the odds of higher lutein intake were greater among those with DR than those without DR. However, after adjusting for confounders, intake of lutein was not associated with DR.</p

Characteristics of the participants, WEB study controls, Erie and Niagara Counties, 1996–2001^a.

<p>Characteristics of the participants, WEB study controls, Erie and Niagara Counties, 1996–2001<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156450#t001fn001" target="_blank">^a</a>.</p

Genetic susceptibility markers for a breast-colorectal cancer phenotype: Exploratory results from genome-wide association studies

<div><p>Background</p><p>Clustering of breast and colorectal cancer has been observed within some families and cannot be explained by chance or known high-risk mutations in major susceptibility genes. Potential shared genetic susceptibility between breast and colorectal cancer, not explained by high-penetrance genes, has been postulated. We hypothesized that yet undiscovered genetic variants predispose to a breast-colorectal cancer phenotype.</p><p>Methods</p><p>To identify variants associated with a breast-colorectal cancer phenotype, we analyzed genome-wide association study (GWAS) data from cases and controls that met the following criteria: cases (n = 985) were women with breast cancer who had one or more first- or second-degree relatives with colorectal cancer, men/women with colorectal cancer who had one or more first- or second-degree relatives with breast cancer, and women diagnosed with both breast and colorectal cancer. Controls (n = 1769), were unrelated, breast and colorectal cancer-free, and age- and sex- frequency-matched to cases. After imputation, 6,220,060 variants were analyzed using the discovery set and variants associated with the breast-colorectal cancer phenotype at <i>P</i><5.0E-04 (n = 549, at 60 loci) were analyzed for replication (n = 293 cases and 2,103 controls).</p><p>Results</p><p>Multiple correlated SNPs in intron 1 of the <i>ROBO1</i> gene were suggestively associated with the breast-colorectal cancer phenotype in the discovery and replication data (most significant; rs7430339, <i>P</i>_discovery = 1.2E-04; rs7429100, <i>P</i>_replication = 2.8E-03). In meta-analysis of the discovery and replication data, the most significant association remained at rs7429100 (<i>P</i> = 1.84E-06).</p><p>Conclusion</p><p>The results of this exploratory analysis did not find clear evidence for a susceptibility locus with a pleiotropic effect on hereditary breast and colorectal cancer risk, although the suggestive association of genetic variation in the region of <i>ROBO1</i>, a potential tumor suppressor gene, merits further investigation.</p></div

Descriptive characteristics of participating genome-wide association studies in the Discovery and Replication analyses.

<p>Descriptive characteristics of participating genome-wide association studies in the Discovery and Replication analyses.</p

Association results for the Discovery, Replication and combined Meta-analysis, for SNPs with <i>P</i><0.05 in the Replication data, by chromosome.

<p>Association results for the Discovery, Replication and combined Meta-analysis, for SNPs with <i>P</i><0.05 in the Replication data, by chromosome.</p

Regional association plots for <i>LHX2</i> and <i>RREB1</i> in GIANT consortium with participants of European ancestry.

<p>The blue arrow points to the index SNPs identified from the samples of African ancestry and red arrow points to the best SNPs in GIANT consortium samples of European ancestry.</p

Interrogation of best SNPs with the smallest p-value within known EA loci in AA for trait WHR ratio adjusted for BMI.

<p>The index SNPs are from Heid et al, Nature Genetics 2010 <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003681#pgen.1003681-Heid1" target="_blank">[17]</a>. Note that <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003681#pgen-1003681-t003" target="_blank"><b>Tables 3</b></a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003681#pgen-1003681-t004" target="_blank"><b>4</b></a> show different information for the same loci (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003681#pgen-1003681-t003" target="_blank"><b>Table 3</b></a> for index SNP and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003681#pgen-1003681-t004" target="_blank"><b>Table 4</b></a> for best SNPs with the smallest p-value).</p>1<p>effect allele/other allele.</p>2<p>effect allele frequency.</p>3<p>number of independent (typed) SNPs interrogated in AA sample.</p>4<p>Bonferroni p-value threshold (0.05/N³).</p>5<p>HapMAP LD information.</p>6<p>one-side test p-value.</p>7<p>P_2GC: double GC-corrected p-value.</p

SNPs associated with waist-related trait at p<5.0E-6 in Stage 1.

1<p>effect allele/other allele.</p>2<p>effect allele frequency.</p>3<p>one-side test p-value.</p>4<p>P_2GC: double GC-corrected p-value.</p

Examination of index SNPs within known loci in EA in AA for trait WHR ratio adjusted for BMI.

<p>The index SNPs is from Heid et al, Nature Genetics 2010 <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003681#pgen.1003681-Heid1" target="_blank">[17]</a>.</p>1<p>effect allele/other allele.</p>2<p>effect allele frequency.</p>3<p>Significance classification refers to the interrogation results of best SNP in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003681#pgen-1003681-t004" target="_blank"><b>Table 4</b></a>.</p>4<p>p-value of heterogeneity test of beta between EA and AA samples.</p

Regional association plots based on single GC-corrected p-value for <i>LHX2</i> and <i>RREB1</i>, Stage 1 only.

<p>MAF = minor allele frequency. The p-values for the index SNP rs2075064 in <i>LHX2</i> loci are 5.5E-8, 0.03, and 2.2E-8 for Stage 1, Stage 2 and joint analysis. The p-values for the index SNP rs6931262 at <i>RREB1</i> loci are 5.3E-8, 0.02 and 2.5E-8 for Stage 1, Stage 2 and joint analysis. The double GC-corrected p-value for the joint analysis are 6.5E-8, 5.7E-8 and 1.8E-6 for rs2075064, rs6931262 and rs1294410, respectively.</p