Clear differences in ovarian cancer incidence and trends by ethnicity among Asian Americans

BackgroundAcross major races in the United States (U.S.), ovarian cancer incidence is low among Asian American women. However, this observation aggregates Asian Americans as a single group despite their heterogeneity. Disaggregating the ethnic Asian population will produce more useful information to better understand ovarian cancer incidence among Asian women in the U.S.MethodsData from the Surveillance, Epidemiology, and End Results Program from 1990 to 2014 were used to compare age-adjusted incidence rates (AAIRs, per 100,000 women) for ovarian cancer for the six largest U.S. Asian ethnicities (Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese) to non-Hispanic whites (NHWs). The race/ethnicity-specific AAIRs were calculated by time period and histotype. We examined the magnitude and direction of AAIR trends using average annual percent change (AAPC) statistics.ResultsAll Asian ethnicities had significantly lower ovarian cancer incidence rates than NHWs. However, among Asian ethnicities, Asian Indians/Pakistanis had the highest rate of ovarian cancer (AAIR = 10.51, 95% CI: 9.65–11.42) while Koreans had the lowest (AAIR = 7.23, 95% CI: 6.62–7.88). Clear cell ovarian cancer had significantly higher incidence rates among Chinese, Filipino, and Japanese women than NHW women (incidence rate ratio (IRR) = 1.49, 95% CI: 1.29–1.72, IRR = 1.30, 95% CI: 1.12–1.51, IRR = 1.64, 95% CI: 1.36–1.97, respectively). Incidence trends also differed by Asian ethnicity with significant decreases only observed for Chinese (AAPC = −1.49, 95% CI: −2.22 to −0.74) and Japanese (AAPC = −1.75, 95% CI: −2.57 to −0.92).ConclusionsExamining Asian Americans as a single group results in missed ethnic-specific disparities in ovarian cancer, hence disaggregating this heterogeneous population in future research is warranted.     

Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort

BackgroundMammographic density is a known heritable risk factor for breast cancer, but reports how tumor characteristics and family history may modify this association are inconsistent.MethodsDense and total breast areas were assessed using Cumulus™ from pre-diagnostic mammograms for 820 invasive breast cancer cases and 820 matched controls nested within the French E3N cohort study. To allow comparisons across models, percent mammographic density (PMD) was standardized to the distribution of the controls. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer risk for mammographic density were estimated by conditional logistic regression while adjusting for age and body mass index. Heterogeneity according to tumor characteristic and family history was assessed using stratified analyses.ResultsOverall, the OR per 1 SD for PMD was 1.50 (95% CI, 1.33–1.69). No evidence for significant heterogeneity by tumor size, lymph node status, grade, and hormone receptor status (estrogen, progesterone, and HER2) was detected. However, the association of PMD was stronger for women reporting a family history of breast cancer (OR_1SD = 2.25; 95% CI, 1.67–3.04) than in women reporting none (OR_1SD = 1.41; 95% CI, 1.24–1.60; p_{heterogeneity} = 0.002). Similarly, effect modification by FHBC was observed using categories of PMD (p_{heterogeneity} = 0.02) with respective ORs of 15.16 (95% CI, 4.23–54.28) vs. 3.14 (95% CI, 1.89–5.22) for ≥50% vs. <10% PMD.ConclusionsThe stronger association between mammographic density and breast cancer risk with a family history supports the hypothesis of shared genetic factors responsible for familial aggregation of breast cancer and the heritable component of mammographic density.     

Ethnic differences in survival after breast cancer in South East Asia

Background

The burden of breast cancer in Asia is escalating. We evaluated the impact of ethnicity on survival after breast cancer in the multi-ethnic region of South East Asia.

Methodology/Principal Findings

Using the Singapore-Malaysia hospital-based breast cancer registry, we analyzed the association between ethnicity and mortality following breast cancer in 5,264 patients diagnosed between 1990 and 2007 (Chinese: 71.6%, Malay: 18.4%, Indian: 10.0%). We compared survival rates between ethnic groups and calculated adjusted hazard ratios (HR) to estimate the independent effect of ethnicity on survival. Malays (n = 968) presented at a significantly younger age, with larger tumors, and at later stages than the Chinese and Indians. Malays were also more likely to have axillary lymph node metastasis at similar tumor sizes and to have hormone receptor negative and poorly differentiated tumors. Five year overall survival was highest in the Chinese women (75.8%; 95%CI: 74.4%–77.3%) followed by Indians (68.0%; 95%CI: 63.8%–72.2%), and Malays (58.5%; 95%CI: 55.2%–61.7%). Compared to the Chinese, Malay ethnicity was associated with significantly higher risk of all-cause mortality (HR: 1.34; 95%CI: 1.19–1.51), independent of age, stage, tumor characteristics and treatment. Indian ethnicity was not significantly associated with risk of mortality after breast cancer compared to the Chinese (HR: 1.14; 95%CI: 0.98–1.34).

Conclusion

In South East Asia, Malay ethnicity is independently associated with poorer survival after breast cancer. Research into underlying reasons, potentially including variations in tumor biology, psychosocial factors, treatment responsiveness and lifestyle after diagnosis, is warranted.     

Mammographic Breast Density and Common Genetic Variants in Breast Cancer Risk Prediction

Introduction

Known prediction models for breast cancer can potentially by improved by the addition of mammographic density and common genetic variants identified in genome-wide associations studies known to be associated with risk of the disease. We evaluated the benefit of including mammographic density and the cumulative effect of genetic variants in breast cancer risk prediction among women in a Singapore population.

Methods

We estimated the risk of breast cancer using a prospective cohort of 24,161 women aged 50 to 64 from Singapore with available mammograms and known risk factors for breast cancer who were recruited between 1994 and 1997. We measured mammographic density using the medio-lateral oblique views of both breasts. Each woman’s genotype for 75 SNPs was simulated based on the genotype frequency obtained from the Breast Cancer Association Consortium data and the cumulative effect was summarized by a genetic risk score (GRS). Any improvement in the performance of our proposed prediction model versus one containing only variables from the Gail model was assessed by changes in receiver-operating characteristic and predictive values.

Results

During 17 years of follow-up, 680 breast cancer cases were diagnosed. The multivariate-adjusted hazard ratios (95% confidence intervals) were 1.60 (1.22–2.10), 2.20 (1.65–2.92), 2.33 (1.71–3.20), 2.12 (1.43–3.14), and 3.27 (2.24–4.76) for the corresponding mammographic density categories: 11-20cm², 21-30cm², 31-40cm², 41-50cm², 51-60cm², and 1.10 (1.03–1.16) for GRS. At the predicted absolute 10-year risk thresholds of 2.5% and 3.0%, a model with mammographic density and GRS could correctly identify 0.9% and 0.5% more women who would develop the disease compared to a model using only the Gail variables, respectively.

Conclusion

Mammographic density and common genetic variants can improve the discriminatory power of an established breast cancer risk prediction model among females in Singapore.     

Beyond Breast Cancer: Mammographic Features and Mortality Risk in a Population of Healthy Women

Background

Breast fibroglandular (dense) tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features.

Methods

We evaluated relationships between nondense (fatty) breast area and dense area with all-cause mortality in 4,245 initially healthy women from the Breast Cancer Detection Demonstration Project; 1,361 died during a mean follow-up of 28.2 years. Dense area and total breast area were assessed using planimeter measurements from screening mammograms. Percent density reflects dense area relative to breast area and nondense area was calculated as the difference between total breast area and dense area. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.

Results

In age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference) while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference). Associations were not attenuated with adjustment for race, education, mammogram type (x-ray or xerogram), smoking status, diabetes and heart disease. With additional adjustment for body mass index, associations were diminished for all features but remained statistically significant for dense area (HR 0.94, 95% CI 0.89-0.99, per SD difference) and percent density (HR 0.93, 95% CI 0.87-0.98, per SD difference).

Conclusions

These data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk.     

The Prevalence of Gestational Diabetes Mellitus Among Asian Females is Lower Using the New 2013 World Health Organization Diagnostic Criteria

ObjectiveTo determine the impact of the new 2013 World Health Organization (WHO) criteria for gestational diabetes mellitus (GDM) diagnosis on GDM prevalence and pregnancy outcomes in Asian ethnic groups compared to the 1999 WHO criteria.MethodsA retrospective cohort study included 855 pregnant females of Chinese, Malay, and Asian Indian ethnicity at high risk of GDM who underwent 75-g oral glucose tolerance tests (OGTTs) between July 2008 and June 2010 in a tertiary center in Singapore. GDM prevalence, reclassification, and pregnancy outcomes were determined using the 2013 and 1999 diagnostic cutoffs for fasting and 2-hour postglucose (PG) values.ResultsThe prevalence of GDM was reduced from 28.8% to 21.1% when the 2013 criteria were used. Overall, 10.2% subjects were reclassified from GDM to normal using the 2013 criteria, and 2.6% were reclassified from normal to GDM, giving a net reclassification rate of 12.8%. Reclassification from GDM to normal was greatest among Chinese, followed by Asian Indians, but the prevalence rate was unchanged among Malays. Babies of mothers who were reclassified from normal to GDM were more likely to have birth weight > 95^th centile and shoulder dystocia.ConclusionThe prevalence of GDM was reduced when the 2013 criteria were used, with the greatest reduction seen among Chinese, followed by Asian Indians. Lowering the fasting cutoff as per the new criteria identified a select group of patients who might benefit from GDM treatment. However, raising the 2-hour PG cutoff would miss a significant number of patients who might potentially benefit from GDM treatment. (Endocr Pract. 2014;20:1064-1069)     

Association of Maternal Vitamin D Status with Glucose Tolerance and Caesarean Section in a Multi-Ethnic Asian Cohort: The Growing Up in Singapore Towards Healthy Outcomes Study

Objective

Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study.

Methods

Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26–28 weeks’ gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section.

Results

In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73).

Conclusions

25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency caesarean section in Chinese and Indian women.     

Changes in Body Composition in Women Following Treatment of Overt and Subclinical Hyperthyroidism

ObjectiveTo determine changes in weight, body composition, and bone density after treatment of overt hyperthyroidism (OH) and subclinical hyperthyroidism (SCH) in women.MethodsWomen with OH and SCH referred to the Mayo Clinic Thyroid Clinic were recruited. Hyperthyroid patients and euthyroid control women were matched for age (within decade) and body mass index. Patients with OH and SCH were treated to normalize thyroid function test results and were restudied after 6 months of normal thyroid function. Baseline and posttreatment studies included measurement of height, weight, bone density, lean mass, fat mass, and thigh muscle cross-sectional area. All participants had normal thyroid function test results for at least 6 months before completion of the posttreatment studies.ResultsTwenty-four patients with OH, 21 patients with SCH, and 36 control patients were studied. In the OH group, fat-free mass increased from a mean of 36.8 kg (95% confidence interval [CI], 34.8-38.8) to 40.4 kg (95% CI, 38.5-42.3); in the SCH group, fat-free mass increased from a mean of 40.3 kg (95% CI, 38.1-42.5) to 42.2 kg (95% CI, 39.7-44.7). In both groups, fat mass increased to approximately the same extent, and both groups experienced significant weight gain with no change in percent body fat. Thigh muscle cross-sectional area increased in both groups—from 100.6 cm² (95% CI, 92.7-108.5) to 113.3 cm² (95% CI, 105.5-121.1) in the OH group and from 106.1 cm² (95% CI, 96.7-115.5) to 112.2 cm² (95% CI, 102.0-122.4) in the SCH group. Bone density increased in patients with OH (P < .01) and in patients with SCH (P < .05).ConclusionsTreatment of OH and SCH leads to increases in muscle area and bone density. Weight gain reflects increases in both fat and fat-free mass. While these results provide some support for actively treating SCH in women, further prospective studies are needed to determine whether the changes documented translate into real patient benefit. (Endocr Pract. 2008;14:973-978)     

Ethnic Differences in the Prevalence of Metabolic Syndrome: Results from a Multi-Ethnic Population-Based Survey in Malaysia

Introduction

The prevalence of metabolic syndrome is increasing disproportionately among the different ethnicities in Asia compared to the rest of the world. This study aims to determine the differences in the prevalence of metabolic syndrome across ethnicities in Malaysia, a multi-ethnic country.

Methods

In 2004, we conducted a national cross-sectional population-based study using a stratified two-stage cluster sampling design (N = 17,211). Metabolic syndrome was defined according to the International Diabetes Federation/National Heart, Lung and Blood Institute/American Heart Association (IDF/NHLBI/AHA-2009) criteria. Multivariate models were used to study the independent association between ethnicity and the prevalence of the metabolic syndrome.

Results

The overall mean age was 36.9 years, and 50.0% participants were female. The ethnic distribution was 57.0% Malay, 28.5% Chinese, 8.9% Indian and 5.0% Indigenous Sarawakians. The overall prevalence of the metabolic syndrome was 27.5%, with a prevalence of central obesity, raised triglycerides, low high density lipoprotein cholesterol, raised blood pressure and raised fasting glucose of 36.9%, 29.3%, 37.2%, 38.0% and 29.1%, respectively. Among those <40 years, the adjusted prevalence ratios for metabolic syndrome for ethnic Chinese, Indians, and Indigenous Sarawakians compared to ethnic Malay were 0.81 (95% CI 0.67 to 0.96), 1.42 (95% CI 1.19 to 1.69) and 1.37 (95% CI 1.08 to 1.73), respectively. Among those aged ≥40 years, the corresponding prevalence ratios were 0.86 (95% CI 0.79 to 0.92), 1.25 (95% CI 1.15 to 1.36), and 0.94 (95% CI 0.80, 1.11). The P-value for the interaction of ethnicity by age was 0.001.

Conclusions

The overall prevalence of metabolic syndrome in Malaysia was high, with marked differences across ethnicities. Ethnic Chinese had the lowest prevalence of metabolic syndrome, while ethnic Indians had the highest. Indigenous Sarawakians showed a marked increase in metabolic syndrome at young ages.     

Head and neck squamous cell carcinomas among males of the three largest Asian diasporas in the US, 2004–2013

BackgroundHead and neck squamous cell carcinomas (HNSCC) have not been fully examined in the Asian diasporas in the US, despite certain Asian countries having the highest incidence of specific HNSCCs.MethodsNational Cancer Database was used to compare 1046 Chinese, 887 South Asian (Indian/Pakistani), and 499 Filipino males to 156,927 Non-Hispanic White (NHW) males diagnosed with HNSCC between 2004−2013. Multinomial logistic regression was used to assess the association of race/ethnicity with two outcomes – site group and late-stage diagnosis. Temporal trends were explored for site groups and subsites.ResultsSouth Asians had a greater proportion of oral cavity cancer [OCC] compared to NHWs (59 % vs. 25 %; OR_adj =7.3 (95 % CI: 5.9–9.0)). In contrast, Chinese (64 % vs. 9%; OR_adj =34.0 (95 % CI: 26.5–43.6)) and Filipinos (47 % vs. 9%; OR_adj =10.0 (95 % CI: 7.8–12.9)) had a greater proportion of non-oropharyngeal cancer compared to NHWs. All three Asian subgroups had a higher likelihood of being diagnosed by age 40 (14 % Chinese, 10 % South Asian and 8% Filipino compared to 3% in NHW; p < 0.001). Chinese males had lower odds of late-stage diagnosis, compared to NHWs. South Asian cases doubled from 2004 to 2013 largely due to an increase in OCC cases (34 cases in 2004 to 86 in 2013).ConclusionAsian diasporas are at a higher likelihood of specific HNSCCs. Risk factors, screening and survival need to be studied further, and policy changes are needed to promote screening and to discourage high-risk habits in these Asian subgroups.     

Ethnic Differences in Visceral Adipose Tissue and Type 2 Diabetes: Filipino,African‐American,and White Women

Objective: To compare ethnic differences in visceral adipose tissue (VAT), assessed by computed tomography, and type 2 diabetes risk among 55‐ to 80‐year‐old Filipino, African‐American, and white women without known cardiovascular disease. Research Methods and Procedures: Subjects were participants in the Rancho Bernardo Study (n = 196), the Filipino Women's Health Study (n = 181), and the Health Assessment Study of African‐American Women (n = 193). Glucose and anthropometric measurements were assessed between 1995 and 2002. Results: African‐American women had significantly higher age‐adjusted BMI (29.7 kg/m²) and waist girth (88.1 cm) compared with Filipino (BMI, 25.5 kg/m²; waist girth, 81.9 cm) or white (BMI: 26.0 kg/m²; waist girth: 80.7 cm) women. However, VAT was significantly higher among Filipino (69.1 cm³) compared with white (62.3 cm³; p = 0.037) or African‐American (57.5 cm³, p < 0.001) women. VAT correlated better with BMI (r = 0.69) and waist (r = 0.77) in whites, compared with Filipino (r = 0.42; r = 0.59) or African‐American (r = 0.50; r = 0.56) women. Age‐adjusted type 2 diabetes prevalence was significantly higher in Filipinas (32.1%) than in white (5.8%) or African‐American (12.1%) women. Filipinas had higher type 2 diabetes risk compared with African Americans [adjusted odds ratio, 2.30; 95% confidence interval (CI), 1.09 to 4.86] or whites (adjusted odds ratio, 7.51; 95% CI, 2.51 to 22.5) after adjusting for age, VAT, exercise, education, and alcohol intake. Discussion: VAT was highest among Filipinas despite similar BMI and waist circumference as whites. BMI and waist circumference were weaker estimates of VAT in Filipino and African‐American women than in whites. Type 2 diabetes prevalence was highest among Filipino women at every level of VAT, but VAT did not explain their elevated type 2 diabetes risk.     

Ethnic variations of a retinoblastoma susceptibility gene (RB1) polymorphism in eight Asian populations

An A → G single nucleotide polymorphism (SNP) at nucleotide 153,104 in the retinoblastoma susceptibility locus (RB1) at 13q14 was previously reported to be present only in Asians. In this study, we determined the distribution of this SNP in normal Southeast Asian populations (Chinese, Malay, Javanese, Thai, Filipino), in South Asian populations (Bangladeshi, Pakistani Pushtun and Indian) and in Chinese retinoblastoma cases and control subjects. TheRB1 SNP was present in all populations at an overall frequency of ≤0.18. Heterozygosity was higher in the Southeast Asian groups (0.14–0.34) than in the South Asian groups (Bangladeshi and Indian) (0.04–0.06). Significant differences in allele frequencies were found between the two population groups. Interestingly, our Pakistani population comprised of ethnic Pushtuns from northwest Pakistan was significantly different from the neighbouring Bangladeshi and Indian populations. No significant difference was found between Chinese case patients and control subjects. ThisRB1 SNP appears to be an ethnic variant prevalent in Southeast Asian populations and may be useful for studyingRB1 inheritance by pedigree analysis.     

Genetic Analysis of the Relationship between Bone Mineral Density and Low-Density Lipoprotein Receptor-Related Protein 5 Gene Polymorphisms

Background

A number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.

Methods

Published literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.

Results

A total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02g/cm², 95% CI = 0.01-0.03, P < 10^-4; at femur neck (FN): WMD = 0.01g/cm², 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02g/cm², 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02g/cm², 95% CI = 0.02-0.03, P < 10^-5; WMD at FN = 0.01g/cm², 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03g/cm², 95% CI = 0.01-0.05, P = 0.005).

Conclusion

This meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.     

Meta‐analysis Added Power to Identify Variants in FTO Associated With Type 2 Diabetes and Obesity in the Asian Population

Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han individuals and conducted a meta‐analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04–1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07–1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04–1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09–1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta‐analysis study (for diabetes, rs8050136, P = 1.3 × 10^?3; rs9939609, P = 9.8 × 10^?4; for obesity, rs8050136, P = 2.2 × 10^?7; rs9939609, P = 9.0 × 10^?9). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.     

Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer

Aim

To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.

Methods

Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31) slides and correlated to mammographic density.

Results

Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22) = 0.5226, p = 0.0088) and significantly inversely associated with adipose tissue proportion (rs (22) = -0.5409, p = 0.0064). Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%). There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026).

Conclusions

The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.     

Is Alanine Aminotransferase Associated with Osteopenia in Middle-Aged and Elderly Chinese?

ObjectivesTo investigate the association between alanine aminotransferase (ALT) levels and risk of osteopenia in middle-aged and elderly Chinese with ALT within the normal range.MethodsThis was a cross-sectional study. A total of 4,890 men and women (pre- and postmenopausal) aged 40 years or older were randomly recruited from Fujian, China. Each participant was required to complete a questionnaire and then undergo anthropometric, biochemical, and bone mineral density measurements.ResultsThe odds ratio of osteopenia decreased significantly with increasing ALT level at baseline. The three groups (men, pre- and postmenopausal women) were divided by ALT quartiles. In multiple logistic regression models using the first quartile as the reference, after adjusting for corresponding confounding factors, the odds ratios of osteopenia across the other ALT quartiles were 0.576 (95% confidence interval [CI], 0.390 to 0.851), 0.654 (95% CI, 0.460 to 0.930), and 0.629 (95% CI, 0.427 to 0.926) for premenopausal women, and 0.949 (95% CI, 0.699 to 1.289), 0.733 (95% CI, 0.540 to 0.995), and 0.692 (95% CI, 0.508 to 0.943) for postmenopausal women (not significant for quartile 2). However, no significantly different results were found in men. Multiple linear regression models showed that serum ALT concentrations were positively associated with the homeostasis model assessment of insulin resistance.ConclusionOur study of middle-aged and elderly Chinese men and women demonstrates that the prevalence of osteopenia is inversely associated with ALT level when ALT is within the normal range. (Endocr Pract. 2014;20: 775-784)     

Uncoupling protein 2 promoter polymorphism -866G/A, central adiposity, and metabolic syndrome in Asians

A polymorphism in the promoter region of uncoupling protein 2 gene -866G/A has been associated with its expression levels in adipose tissue, the risk of obesity, and metabolic abnormalities. Our purpose was to examine the associations of -866G/A with body fat and the risk of metabolic syndrome in a random sample of 4018 Asians (1858 men and 2160 women) from three ethnic groups (Chinese, Malay, and Indian). The minor allele frequency of -866G/A polymorphism in South Asians was similar to that in whites. After adjustment for covariates including age, cigarette smoking, and physical activity, the -866A/A genotype was associated with higher waist-to-hip ratio as compared with the wild-type genotype in Chinese and Indian men (p = 0.018 and p = 0.046, respectively). Moreover, Indian men with -866A/A genotype had a significantly increased risk of metabolic syndrome as compared with those homozygous for the wild-type (odds ratio, 2.66; 95% confidence interval, 1.21 to 5.88; p = 0.015). Such a risk was mainly caused by the excess presence of hypertriglyceridemia and central obesity. Our findings indicate that the uncoupling protein 2 gene -866G/A polymorphism may increase the risks of central obesity and metabolic syndrome, with greater effects on Asian men.     

Ethnic Variation in the Correlation Between Fasting Glucose Concentration and Glycated Hemoglobin (HbA1C)

ObjectiveWe aimed to determine the relationship between fasting serum glucose (FSG) concentration and glycated hemoglobin-Alc (HbAlc) in the 3 ethnicities in Singapore after adjustment for demographic and therapeutic variables.MethodsFasting serum glucose (FSG), HbAlc, and serum creatinine levels were simultaneously sampled from 575 patients with diabetes (389 Chinese, 97 Indians, 89 Malays) in this cross-sectional study between January and May 2008, and the results were subjected to multivariate linear regression analysis.ResultsWe found a significant interaction between FSG and ethnicity on HbAlc. The correlation between FSG and HbAlc among Chinese subjects was 0.25 (95% confidence interval [CI]:0.2-0.3) relative to the Malays (0.38, 95% CI: 0.30-0.45) after adjustment for age; gender; serum creatinine concentrations; body mass index (BMI); duration of diabetes; use of sulfonylureas, metformin, and insulin; and hemoglobin (Hb) and red cell indices (P = .005). Hence, for a given FSG, the predicted HbAlc will be higher in Malays compared to Chinese subjects.We did not observe a statistically significant difference between Indians and Malays with respect to the correlation between FSG and HbAlc.ConclusionWe showed a higher correlation between HbAlc and FSG in Malay subjects relative to the Chinese in this cohort. The ethnic variation in the HbAlc-FSG relationship may be related to differences in percentage contribution by the FSG to overall HbAlc among ethnic groups. Future studies using continuous glucose monitoring (CGM) to elucidate the relative contributions by FSG and postprandial glucose (PPG) to the daily blood glucose profile and the overall HbA1c by ethnicity are required. (Endocr Pract. 2013;19:812-817)     

Determinants and Effects of Voice Disorders among Secondary School Teachers in Peninsular Malaysia Using a Validated Malay Version of VHI-10

Objectives

To establish the prevalence of voice disorder using the Malay-Voice Handicap Index 10 (Malay-VHI-10) and to study the determinants, quality of life, depression, anxiety and stress associated with voice disorder among secondary school teachers in Peninsular Malaysia.

Methods

This study was divided into two phases. Phase I tested the reliability of the Malay-VHI-10 while Phase II was a cross-sectional study with two-stage sampling. In Phase II, a self-administered questionnaire was used to collect socio-demographic and teaching characteristics, depression, anxiety and stress scale (Malay version of DASS-21); and health-related quality of life (Malay version of SF12-v2). Complex sample analysis was conducted using multivariate Poisson regression with robust variance.

Results

In Phase I, the Spearman correlation coefficient and Cronbach alpha for total VHI-10 score was 0.72 (p < 0.001) and 0.77 respectively; showing good correlation and internal consistency. The ICCs ranged from 0.65 to 0.78 showing fair to good reliability and demonstrating the subscales to be reliable and stable. A total of 6039 teachers participated in Phase II. They were primarily Malays, females, married, had completed tertiary education and aged between 30 to 50 years. A total of 10.4% (95% CI 7.1, 14.9) of the teachers had voice disorder (VHI-10 score > 11). Compared to Malays, a greater proportion of ethnic Chinese teachers reported voice disorder while ethnic Indian teachers were less likely to report this problem. There was a higher prevalence ratio (PR) of voice disorder among single or divorced/widowed teachers. Teachers with voice disorder were more likely to report higher rates of absenteeism (PR: 1.70, 95% CI 1.33, 2.19), lower quality of life with lower SF12-v2 physical (0.98, 95% CI 0.96, 0.99) and mental (0.97, 95% CI 0.96, 0.98) component summary scales; and higher anxiety levels (1.04, 95% CI 1.02, 1.06).

Conclusions

The Malay-VHI-10 is valid and reliable. Voice disorder was associated with increased absenteeism, marginally associated with reduced health-related quality of life as well as increased anxiety among teachers.     

Ethnic differences in guideline-indicated statin initiation for people with type 2 diabetes in UK primary care, 2006–2019: A cohort study

BackgroundType 2 diabetes is 2–3 times more prevalent in people of South Asian and African/African Caribbean ethnicity than people of European ethnicity living in the UK. The former 2 groups also experience excess atherosclerotic cardiovascular disease (ASCVD) complications of diabetes. We aimed to study ethnic differences in statin initiation, a cornerstone of ASCVD primary prevention, for people with type 2 diabetes.Methods and findingsObservational cohort study of UK primary care records, from 1 January 2006 to 30 June 2019. Data were studied from 27,511 (88%) people of European ethnicity, 2,386 (8%) people of South Asian ethnicity, and 1,142 (4%) people of African/African Caribbean ethnicity with incident type 2 diabetes, no previous ASCVD, and statin use indicated by guidelines. Statin initiation rates were contrasted by ethnicity, and the number of ASCVD events that could be prevented by equalising prescribing rates across ethnic groups was estimated. Median time to statin initiation was 79, 109, and 84 days for people of European, South Asian, and African/African Caribbean ethnicity, respectively. People of African/African Caribbean ethnicity were a third less likely to receive guideline-indicated statins than European people (n/N [%]: 605/1,142 [53%] and 18,803/27,511 [68%], respectively; age- and gender-adjusted HR 0.67 [95% CI 0.60 to 0.76], p < 0.001). The HR attenuated marginally in a model adjusting for total cholesterol/high-density lipoprotein cholesterol ratio (0.77 [95% CI 0.69 to 0.85], p < 0.001), with no further diminution when deprivation, ASCVD risk factors, comorbidity, polypharmacy, and healthcare usage were accounted for (fully adjusted HR 0.76 [95% CI 0.68, 0.85], p < 0.001). People of South Asian ethnicity were 10% less likely to receive a statin than European people (1,489/2,386 [62%] and 18,803/27,511 [68%], respectively; fully adjusted HR 0.91 [95% CI 0.85 to 0.98], p = 0.008, adjusting for all covariates). We estimated that up to 12,600 ASCVD events could be prevented over the lifetimes of people currently affected by type 2 diabetes in the UK by equalising statin prescribing across ethnic groups. Limitations included incompleteness of recording of routinely collected data.ConclusionsIn this study we observed that people of African/African Caribbean ethnicity with type 2 diabetes were substantially less likely, and people of South Asian ethnicity marginally less likely, to receive guideline-indicated statins than people of European ethnicity, even after accounting for sociodemographics, healthcare usage, ASCVD risk factors, and comorbidity. Underuse of statins in people of African/African Caribbean or South Asian ethnicity with type 2 diabetes is a missed opportunity to prevent cardiovascular events.

In a retrospective cohort study, Sophie Eastwood and colleagues investigate the association between ethnicity and statin initiation for people with type 2 diabetes in UK.