METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).
RESULTS: We observed no significant association between genetic variants and prostate cancer survival.
CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study.
IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.
OBJECTIVE: To assess the chronic effects of the substitution of refined carbohydrate or MUFA for SAFA on insulin secretion and insulin sensitivity in centrally obese subjects.
METHODS: Using a crossover design, randomized controlled trial in abdominally overweight men and women, we compared the effects of substitution of 7% energy as carbohydrate or MUFA for SAFA for a period of 6 weeks each. Fasting and postprandial blood samples in response to corresponding SAFA, carbohydrate, or MUFA-enriched meal-challenges were collected after 6 weeks on each diet treatment for the assessment of outcomes.
RESULTS: As expected, postprandial nonesterified fatty acid suppression and elevation of C-peptide, insulin and glucose secretion were the greatest with high-carbohydrate (CARB) meal. Interestingly, CARB meal attenuated postprandial insulin secretion corrected for glucose response; however, the insulin sensitivity and disposition index were not affected. SAFA and MUFA had similar effects on all markers except for fasting glucose-dependent insulinotropic peptide concentrations, which increased after MUFA but not SAFA when compared with CARB.
CONCLUSION: In conclusion, a 6-week lower-fat/higher-carbohydrate (increased by 7% refined carbohydrate) diet may have greater adverse effect on insulin secretion corrected for glucose compared with isocaloric higher-fat diets. In contrast, exchanging MUFA for SAFA at 7% energy had no appreciable adverse impact on insulin secretion.
Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.
Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.
Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.
Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.
MATERIALS AND METHODS: Seventy-five premolars devoid of dental caries that were subjected to extraction for orthodontic purposes were employed in this research. The surface of enamel was etched with 37% phosphoric acid and subjected to primer application. Individual brackets were placed on the midregion of the buccal surfaces of the premolars with Transbond™ XT adhesive. Postbracket bonding, the dry premolar tooth samples were set aside cautiously. The samples were then allocated to three groups: Group I: Duraphat Varnish, Group II: Clinpro XT Varnish, and Group III: Profluorid Varnish. Every sample was independently subjected to immersion in demineralizing solution for a period of 96 h at 37°C in an incubator. Areas of demineralization were evaluated by documenting the microhardness along the severed surface using a microhardness tester equipped with a Vickers diamond.
RESULTS: The highest surface microhardness was noted with Profluorid Varnish group at 328.48 ± 1.12 in pursuit by Clinpro XT Varnish group at 322.08 ± 0.04 as well as Duraphat Varnish group at 307.42 ± 0.28 with a statistically noteworthy dissimilarity amid the groups.
CONCLUSION: In conclusion, the three varnishes employed had an influence on the prevention of enamel demineralization surrounding the orthodontic brackets. Profluorid varnish however exhibited maximum efficiency in avoiding enamel demineralization versus Clinpro XT varnish as well as Duraphat varnish group.
METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.