The contribution of diet and genotype to iron status in women:a classical twin study

This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04)

Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue

PURPOSE: Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. METHODS: We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. RESULTS: Fourteen percent of evaluated SNPs (8 SNPs) were associated with TDLU counts at p<0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50% that were either significantly or nonsignficantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among 10 SNPs that were statistically significantly associated with at least one TDLU involution measure (p<0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. CONCLUSIONS: Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results

Detection of quantitative trait loci controlling bud burst and height growth in Quercus robur L.

Genetic variation of bud burst and early growth components was estimated in a full-sib family of Quercus robur L. comprising 278 offspring. The full sibs were vegetatively propagated, and phenotypic assessments were made in three field tests. This two-generation pedigree was also used to construct a genetic linkage map (12 linkage groups, 128 markers) and locate quantitative trait loci (QTLs) controlling bud burst and growth components. In each field test, the date of bud burst extended over a period of 20 days from the earliest to the latest clone. Bud burst exhibited higher heritability (0.15–0.51) than growth components (0.04–0.23) and also higher correlations across field tests. Over the three tests there were 32 independent detected QTLs (Ple5% at the chromosome level) controlling bud burst, which likely represent at least 12 unique genes or chromosomal regions controlling this trait. QTLs explained from 3% to 11% of the variance of the clonal means. The number of QTLs controlling height growth components was lower and varied between two and four. However the contribution of each QTL to the variance of the clonal mean was higher (from 4% to 19%). These results indicate that the genetic architecture of two important fitness-related traits are quite different. On the one hand, bud burst is controlled by several QTLs with rather low to moderate effects, but contributing to a high genetic (additive) variance. On the other hand, height growth depends on fewer QTLs with moderate to strong effects, resulting in lower heritabilities of the trai

Standardized measures of lobular involution and subsequent breast cancer risk among women with benign breast disease: a nested case–control study

Lesser degrees of terminal duct-lobular unit (TDLU) involution predict higher breast cancer risk; however, standardized measures to quantitate levels of TDLU involution have only recently been developed. We assessed whether three standardized measures of TDLU involution, with high intra/inter pathologist reproducibility in normal breast tissue, predict subsequent breast cancer risk among women in the Mayo benign breast disease (BBD) cohort. We performed a masked evaluation of biopsies from 99 women with BBD who subsequently developed breast cancer (cases) after a median of 16.9 years and 145 age-matched controls. We assessed three metrics inversely related to TDLU involution: TDLU count/mm(2), median TDLU span (microns, which approximates acini content), and median category of acini counts/TDLU (0–10; 11–20; 21–30; 31–50; >50). Associations with subsequent breast cancer risk for quartiles (or categories of acini counts) of each of these measures were assessed with multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI). In multivariable models, women in the highest quartile compared to the lowest quartiles of TDLU counts and TDLU span measures were significantly associated with subsequent breast cancer diagnoses; TDLU counts quartile4 versus quartile1, OR = 2.44, 95 %CI 0.96–6.19, p-trend = 0.02; and TDLU spans, quartile4 versus quartile1, OR = 2.83, 95 %CI = 1.13–7.06, p-trend = 0.03. Significant associations with categorical measures of acini counts/TDLU were also observed: compared to women with median category of <10 acini/TDLU, women with >25 acini counts/TDLU were at significantly higher risk, OR = 3.40, 95 %CI 1.03–11.17, p-trend = 0.032. Women with TDLU spans and TDLU count measures above the median were at further increased risk, OR = 3.75 (95 %CI 1.40–10.00, p-trend = 0.008), compared with women below the median for both of these metrics. Similar results were observed for combinatorial metrics of TDLU acini counts/TDLU, and TDLU count. Standardized quantitative measures of TDLU counts and acini counts approximated by TDLU span measures or visually assessed in categories are independently associated with breast cancer risk. Visual assessment of TDLU numbers and acini content, which are highly reproducible between pathologists, could help identify women at high risk for subsequent breast cancer among the million women diagnosed annually with BBD in the US