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Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

Background:Ovarian cancer incidence differs substantially by race/ethnicity, but the reasons for this are not well understood. Data were pooled from the African American Cancer Epidemiology Study (AACES) and 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC) to examine racial/ethnic differences in epidemiological characteristics with suspected involvement in epithelial ovarian cancer (EOC) aetiology. Methods:We used multivariable logistic regression to estimate associations for 17 reproductive, hormonal and lifestyle characteristics and EOC risk by race/ethnicity among 10 924 women with invasive EOC (8918 Non-Hispanic Whites, 433 Hispanics, 911 Blacks, 662 Asian/Pacific Islanders) and 16 150 controls (13 619 Non-Hispanic Whites, 533 Hispanics, 1233 Blacks, 765 Asian/Pacific Islanders). Likelihood ratio tests were used to evaluate heterogeneity in the risk factor associations by race/ethnicity. Results:We observed statistically significant racial/ethnic heterogeneity for hysterectomy and EOC risk (P = 0.008), where the largest odds ratio (OR) was observed in Black women [OR = 1.64, 95% confidence interval (CI) = 1.34-2.02] compared with other racial/ethnic groups. Although not statistically significant, the associations for parity, first-degree family history of ovarian or breast cancer, and endometriosis varied by race/ethnicity. Asian/Pacific Islanders had the greatest magnitude of association for parity (≥3 births: OR = 0.38, 95% CI = 0.28-0.54), and Black women had the largest ORs for family history (OR = 1.77, 95% CI = 1.42-2.21) and endometriosis (OR = 2.42, 95% CI = 1.65-3.55). Conclusions:Although racial/ethnic heterogeneity was observed for hysterectomy, our findings support the validity of EOC risk factors across all racial/ethnic groups, and further suggest that any racial/ethnic population with a higher prevalence of a modifiable risk factor should be targeted to disseminate information about prevention.

One of the authors did not declare a potential conflict of interest. The statement in the article should have read: “Conflict of interest: Patricia Moorman has received compensation for work related to litigation in regard to talc and ovarian cancer. The other authors declare no conflicts"

BackgroundOvarian cancer incidence differs substantially by race/ethnicity, but the reasons for this are not well understood. Data were pooled from the African American Cancer Epidemiology Study (AACES) and 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC) to examine racial/ethnic differences in epidemiological characteristics with suspected involvement in epithelial ovarian cancer (EOC) aetiology.MethodsWe used multivariable logistic regression to estimate associations for 17 reproductive, hormonal and lifestyle characteristics and EOC risk by race/ethnicity among 10 924 women with invasive EOC (8918 Non-Hispanic Whites, 433 Hispanics, 911 Blacks, 662 Asian/Pacific Islanders) and 16 150 controls (13 619 Non-Hispanic Whites, 533 Hispanics, 1233 Blacks, 765 Asian/Pacific Islanders). Likelihood ratio tests were used to evaluate heterogeneity in the risk factor associations by race/ethnicity.ResultsWe observed statistically significant racial/ethnic heterogeneity for hysterectomy and EOC risk (P = 0.008), where the largest odds ratio (OR) was observed in Black women [OR = 1.64, 95% confidence interval (CI) = 1.34-2.02] compared with other racial/ethnic groups. Although not statistically significant, the associations for parity, first-degree family history of ovarian or breast cancer, and endometriosis varied by race/ethnicity. Asian/Pacific Islanders had the greatest magnitude of association for parity (≥3 births: OR = 0.38, 95% CI = 0.28-0.54), and Black women had the largest ORs for family history (OR = 1.77, 95% CI = 1.42-2.21) and endometriosis (OR = 2.42, 95% CI = 1.65-3.55).ConclusionsAlthough racial/ethnic heterogeneity was observed for hysterectomy, our findings support the validity of EOC risk factors across all racial/ethnic groups, and further suggest that any racial/ethnic population with a higher prevalence of a modifiable risk factor should be targeted to disseminate information about prevention.

BackgroundNutritional risk and low BMI are common among community-dwelling older adults, but it is unclear what associations these factors have with health services utilization and mortality over long-term follow-up. The aim of this study was to assess prospective associations of nutritional risk and BMI with all-cause, nonsurgical, and surgical hospitalization; nursing home admission; and mortality over 8.5 years.MethodsData are from 1,000 participants in the University of Alabama at Birmingham Study of Aging, a longitudinal, observational study of older black and white residents of Alabama aged 65 and older. Nutritional risk was assessed using questions associated with the DETERMINE checklist. BMI was categorized as underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), class I obese (30.0-34.9), and classes II and III obese (≥35.0). Cox proportional hazards models were fit to assess risk of all-cause, nonsurgical, and surgical hospitalization; nursing home admission; and mortality. Covariates included social support, social isolation, comorbidities, and demographic measures.ResultsIn adjusted models, persons with high nutritional risk had 51% greater risk of all-cause hospitalization (95% confidence interval: 1.14-2.00) and 50% greater risk of nonsurgical hospitalizations (95% confidence interval: 1.11-2.01; referent: low nutritional risk). Persons with moderate nutritional risk had 54% greater risk of death (95% confidence interval: 1.19-1.99). BMI was not associated with any outcomes in adjusted models.ConclusionsNutritional risk was associated with all-cause hospitalizations, nonsurgical hospitalizations, and mortality. Nutritional risk may affect the disablement process that leads to health services utilization and death. These findings point to the need for more attention on nutritional assessment, interventions, and services for community-dwelling older adults.

BackgroundNutritional risk and low BMI are common among community-dwelling older adults, but it is unclear what associations these factors have with health services utilization and mortality over long-term follow-up. The aim of this study was to assess prospective associations of nutritional risk and BMI with all-cause, nonsurgical, and surgical hospitalization; nursing home admission; and mortality over 8.5 years.MethodsData are from 1,000 participants in the University of Alabama at Birmingham Study of Aging, a longitudinal, observational study of older black and white residents of Alabama aged 65 and older. Nutritional risk was assessed using questions associated with the DETERMINE checklist. BMI was categorized as underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), class I obese (30.0-34.9), and classes II and III obese (≥35.0). Cox proportional hazards models were fit to assess risk of all-cause, nonsurgical, and surgical hospitalization; nursing home admission; and mortality. Covariates included social support, social isolation, comorbidities, and demographic measures.ResultsIn adjusted models, persons with high nutritional risk had 51% greater risk of all-cause hospitalization (95% confidence interval: 1.14-2.00) and 50% greater risk of nonsurgical hospitalizations (95% confidence interval: 1.11-2.01; referent: low nutritional risk). Persons with moderate nutritional risk had 54% greater risk of death (95% confidence interval: 1.19-1.99). BMI was not associated with any outcomes in adjusted models.ConclusionsNutritional risk was associated with all-cause hospitalizations, nonsurgical hospitalizations, and mortality. Nutritional risk may affect the disablement process that leads to health services utilization and death. These findings point to the need for more attention on nutritional assessment, interventions, and services for community-dwelling older adults.

OBJECTIVE: Estimate the proportion of dental practitioners who use online sources of information for practice guidance.METHODS: From a survey of 657 dental practitioners in The Dental Practice-Based Research Network, four indicators of online use for practice guidance were calculated: read journals online, obtained continuing education (CDE) through online sources, rated an online source as most influential, and reported frequently using an online source for guidance. Demographics, journals read, and use of various sources of information for practice guidance in terms of frequency and influence were ascertained for each.RESULTS: Overall, 21 percent (n = 138) were classified into one of the four indicators of online use: 14 percent (n = 89) rated an online source as most influential and 13 percent (n = 87) reported frequently using an online source for guidance; few practitioners (5 percent, n = 34) read journals online, fewer (3 percent, n = 17) obtained CDE through online sources. Use of online information sources varied considerably by region and practice characteristics. In general, the four indicators represented practitioners with as many differences as similarities to each other and to offline users.CONCLUSION: A relatively small proportion of dental practitioners use information from online sources for practice guidance. Variation exists regarding practitioners' use of online source resources and how they rate the value of offline information sources for practice guidance.

BACKGROUND: A questionable occlusal caries (QOC) lesion can be defined as an occlusal surface with no radiographic evidence of caries, but caries is suspected because of clinical appearance. In this study, the authors report the results of a 20-month follow-up of these lesions.METHODS: Fifty-three clinicians from The National Dental Practice-Based Research Network participated in this study, recording lesion characteristics at baseline and lesion status at 20 months.RESULTS: At baseline, 1,341 QOC lesions were examined; the treatment that was planned for 1,033 of those at baseline was monitoring (oral hygiene instruction, applying or prescribing fluoride or varnish, or both), and the remaining 308 received a sealant (n = 192) or invasive therapy (n = 116). At the 20-month visit, clinicians continued to monitor 927 (90 percent) of the 1,033 monitored lesions. Clinicians decided to seal 61 (6 percent) of the 1,033 lesions (mean follow-up, 19 months) and invasively treat 45 (4 percent) of them (mean follow-up, 15 months). Young patient age (< 18 years) (odds ratio = 3.4; 95 percent confidence interval, 1.7-6.8) and the lesion's being on a molar (odds ratio = 1.8; 95 percent confidence interval, 1.3-2.6) were associated with the clinician's deciding at some point after follow-up to seal the lesion or treat it invasively.CONCLUSIONS: Almost all (90 percent) QOC lesions for which the treatment planned at baseline was monitoring still were planned to undergo monitoring after 20 months. This finding suggests that noninvasive management is appropriate for these lesions.PRACTICAL IMPLICATIONS: Previous study results from baseline indicated a high prevalence of QOC lesions (34 percent). Clinicians should consider long-term monitoring when making treatment decisions about these lesions.

OBJECTIVE: Estimate the proportion of dental practitioners who use online sources of information for practice guidance.METHODS: From a survey of 657 dental practitioners in The Dental Practice-Based Research Network, four indicators of online use for practice guidance were calculated: read journals online, obtained continuing education (CDE) through online sources, rated an online source as most influential, and reported frequently using an online source for guidance. Demographics, journals read, and use of various sources of information for practice guidance in terms of frequency and influence were ascertained for each.RESULTS: Overall, 21 percent (n = 138) were classified into one of the four indicators of online use: 14 percent (n = 89) rated an online source as most influential and 13 percent (n = 87) reported frequently using an online source for guidance; few practitioners (5 percent, n = 34) read journals online, fewer (3 percent, n = 17) obtained CDE through online sources. Use of online information sources varied considerably by region and practice characteristics. In general, the four indicators represented practitioners with as many differences as similarities to each other and to offline users.CONCLUSION: A relatively small proportion of dental practitioners use information from online sources for practice guidance. Variation exists regarding practitioners' use of online source resources and how they rate the value of offline information sources for practice guidance.

BACKGROUND: A questionable occlusal caries (QOC) lesion can be defined as an occlusal surface with no radiographic evidence of caries, but caries is suspected because of clinical appearance. In this study, the authors report the results of a 20-month follow-up of these lesions.METHODS: Fifty-three clinicians from The National Dental Practice-Based Research Network participated in this study, recording lesion characteristics at baseline and lesion status at 20 months.RESULTS: At baseline, 1,341 QOC lesions were examined; the treatment that was planned for 1,033 of those at baseline was monitoring (oral hygiene instruction, applying or prescribing fluoride or varnish, or both), and the remaining 308 received a sealant (n = 192) or invasive therapy (n = 116). At the 20-month visit, clinicians continued to monitor 927 (90 percent) of the 1,033 monitored lesions. Clinicians decided to seal 61 (6 percent) of the 1,033 lesions (mean follow-up, 19 months) and invasively treat 45 (4 percent) of them (mean follow-up, 15 months). Young patient age (< 18 years) (odds ratio = 3.4; 95 percent confidence interval, 1.7-6.8) and the lesion's being on a molar (odds ratio = 1.8; 95 percent confidence interval, 1.3-2.6) were associated with the clinician's deciding at some point after follow-up to seal the lesion or treat it invasively.CONCLUSIONS: Almost all (90 percent) QOC lesions for which the treatment planned at baseline was monitoring still were planned to undergo monitoring after 20 months. This finding suggests that noninvasive management is appropriate for these lesions.PRACTICAL IMPLICATIONS: Previous study results from baseline indicated a high prevalence of QOC lesions (34 percent). Clinicians should consider long-term monitoring when making treatment decisions about these lesions.

Knowing which factors influence restoration longevity can help clinicians make sound treatment decisions. The authors analyzed data from The National Dental Practice-Based Research Network to identify predictors of early failures of amalgam and resin-based composite (RBC) restorations.

Knowing which factors influence restoration longevity can help clinicians make sound treatment decisions. The authors analyzed data from The National Dental Practice-Based Research Network to identify predictors of early failures of amalgam and resin-based composite (RBC) restorations.

Questionable occlusal caries (QOC) can be defined as clinically suspected caries with no cavitation or radiographic evidence of occlusal caries. To the authors' knowledge, no one has quantified the prevalence of QOC, so this quantification was the authors' objective in conducting this study

OBJECTIVES: Practice-based research networks (PBRNs) provide a venue to foster evidence-based care. We tested the hypothesis that a higher level of participation in a dental PBRN is associated with greater stated change toward evidence-based practice. METHODS: A total of 565 dental PBRN practitioner-investigators completed a baseline questionnaire entitled 'Assessment of Caries Diagnosis and Treatment'; 405 of these also completed a follow-up questionnaire about treatment of caries and existing restorations. Certain questions (six treatment scenarios) were repeated at follow-up a mean (SD) of 36.0 (3.8) months later. A total of 224 were 'full participants' (enrolled in clinical studies and attended at least one network meeting); 181 were 'partial participants' (did not meet 'full' criteria). RESULTS: From 10% to 62% of practitioners were 'surgically invasive' at baseline, depending on the clinical scenario. Stated treatment approach was significantly less invasive at follow-up for four of six items. Change was greater among full participants and those with a more-invasive approach at baseline, with an overall pattern of movement away from the extremes. CONCLUSIONS: These results are consistent with a preliminary conclusion that network participation fostered movement of scientific evidence into routine practice. PBRNs may foster movement of evidence into everyday practice as practitioners become engaged in the scientific process.

OBJECTIVES: Practice-based research networks (PBRNs) provide a venue to foster evidence-based care. We tested the hypothesis that a higher level of participation in a dental PBRN is associated with greater stated change toward evidence-based practice. METHODS: A total of 565 dental PBRN practitioner-investigators completed a baseline questionnaire entitled 'Assessment of Caries Diagnosis and Treatment'; 405 of these also completed a follow-up questionnaire about treatment of caries and existing restorations. Certain questions (six treatment scenarios) were repeated at follow-up a mean (SD) of 36.0 (3.8) months later. A total of 224 were 'full participants' (enrolled in clinical studies and attended at least one network meeting); 181 were 'partial participants' (did not meet 'full' criteria). RESULTS: From 10% to 62% of practitioners were 'surgically invasive' at baseline, depending on the clinical scenario. Stated treatment approach was significantly less invasive at follow-up for four of six items. Change was greater among full participants and those with a more-invasive approach at baseline, with an overall pattern of movement away from the extremes. CONCLUSIONS: These results are consistent with a preliminary conclusion that network participation fostered movement of scientific evidence into routine practice. PBRNs may foster movement of evidence into everyday practice as practitioners become engaged in the scientific process.

Questionable occlusal caries (QOC) can be defined as clinically suspected caries with no cavitation or radiographic evidence of occlusal caries. To the authors' knowledge, no one has quantified the prevalence of QOC, so this quantification was the authors' objective in conducting this study

BACKGROUND: Multiple uncontrolled medical conditions may act as competing demands for clinical decision making. We hypothesized that multiple uncontrolled cardiovascular risk factors would decrease blood pressure (BP) medication intensification among uncontrolled hypertensive patients. METHODS: We observed 946 encounters at two VA primary care clinics from May through August 2006. After each encounter, clinicians recorded BP medication intensification (BP medication was added or titrated). Demographic, clinical, and laboratory information were collected from the medical record. We examined BP medication intensification by presence and control of diabetes and/or hyperlipidemia. 'Uncontrolled' was defined as hemoglobin A1c >/= for diabetes, BP >/= 140/90 mmHg (>/= 130/80 mmHg if diabetes present) for hypertension, and low density lipoprotein cholesterol (LDL-c) >/= 130 mg/dl (>/= 100 mg/dl if diabetes present) for hyperlipidemia. Hierarchical regression models accounted for patient clustering and adjusted medication intensification for age, systolic BP, and number of medications. RESULTS: Among 387 patients with uncontrolled hypertension, 51.4% had diabetes (25.3% were uncontrolled) and 73.4% had hyperlipidemia (22.7% were uncontrolled). The BP medication intensification rate was 34.9% overall, but higher in individuals with uncontrolled diabetes and uncontrolled hyperlipidemia: 52.8% overall and 70.6% if systolic BP >/= 10 mmHg above goal. Intensification rates were lowest if diabetes or hyperlipidemia were controlled, lower than if diabetes or hyperlipidemia were not present. Multivariable adjustment yielded similar results. CONCLUSIONS: The presence of uncontrolled diabetes and hyperlipidemia was associated with more guideline-concordant hypertension care, particularly if BP was far from goal. Efforts to understand and improve BP medication intensification in patients with controlled diabetes and/or hyperlipidemia are warranted.