Early-Life Factors and Early-Onset Endometrial Cancer Risk in the UK Biobank.

This case-control study investigates UK Biobank data for 8 early-life factors and early-onset endometrial cancer risk among UK residents.

The association of a healthy lifestyle index and imaging-based body fat distribution with glycemic status and Type 2 diabetes in the Multi Ethnic Cohort: a cross-sectional analysis.

INTRODUCTION: As several behaviors captured by the Lifestyle Risk Factor Index (LSRI) are protective against Type 2 diabetes (T2D) and may affect body fat distribution, we examined its relation with both outcomes. METHODS: In a subset of the Multiethnic Cohort, participants from five ethnic groups (60-77 years) were assigned LSRI scores (one point each for consuming <1 (women)/<2 (men) alcoholic drinks/day, ≥1.5 physical activity hours/week, not smoking, and adhering to ≥3/7 dietary recommendations). All participants completed an extensive Quantitative Food Frequency Questionnaire to allow estimation of adherence to intake recommendations for fruits, vegetables, refined and whole grains, fish, processed and non-processed meat. Glycemic/T2D status was classified according to self-reports and fasting glucose. We estimated prevalence odds ratios (POR) of LSRI with glycemic/T2D status and DXA- and MRI-based body fat distribution using logistic regression. RESULTS: Of 1713 participants, 43% had normoglycemia, 30% Pre-T2D, 9% Undiagnosed T2D, and 18% T2D. Overall, 39% scored 0-2, 49% 3, and 12% 4 LSRI points. T2D prevalence was 55% (POR 0.45; 95% confidence intervals 0.27, 0.76) lower for 4 vs. 0-2 LSRI points with weaker associations for abnormal glycemic status. Despite the low adherence to dietary recommendations (22%), this was the only component related to lower T2D prevalence. The inverse LSRI-T2D association was only observed among Latinos and Japanese Americans in ethnic-specific models. Visceral fat measures were higher in T2D patients and attenuated the LSRI-T2D association. CONCLUSION: These findings support the role of a healthy lifestyle, especially diet, in T2D prevention with differences across ethnicity.

Menopausal hormone therapy use and risk of ovarian cancer by race: the ovarian cancer in women of African ancestry consortium.

BACKGROUND: Most studies examining post-menopausal menopausal hormone therapy (MHT) use and ovarian cancer risk have focused on White women and few have included Black women. METHODS: We evaluated MHT use and ovarian cancer risk in Black (n = 800 cases, 1783 controls) and White women (n = 2710 cases, 8556 controls), using data from the Ovarian Cancer in Women of African Ancestry consortium. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MHT use with ovarian cancer risk, examining histotype, MHT type and duration of use. RESULTS: Long-term MHT use, ≥10 years, was associated with an increased ovarian cancer risk for White women (OR = 1.38, 95%CI: 1.22-1.57) and the association was consistent for Black women (OR = 1.20, 95%CI: 0.81-1.78, pinteraction = 0.4). For White women, the associations between long-term unopposed estrogen or estrogen plus progesterone use and ovarian cancer risk were similar; the increased risk associated with long-term MHT use was confined to high-grade serous and endometroid tumors. Based on smaller numbers for Black women, the increased ovarian cancer risk associated with long-term MHT use was apparent for unopposed estrogen use and was predominately confined to other epithelial histotypes. CONCLUSION: The association between long-term MHT use and ovarian cancer risk was consistent for Black and White women.

Transcriptional Profile of Human Pancreatic Acinar Ductal Metaplasia.

BACKGROUND AND AIMS: Aberrant acinar to ductal metaplasia (ADM), one of the earliest events involved in exocrine pancreatic cancer development, is typically studied using pancreata from genetically engineered mouse models. METHODS: We used primary, human pancreatic acinar cells from organ donors to evaluate the transcriptional and pathway profiles during the course of ADM. RESULTS: Following 6 days of three-dimensional culture on Matrigel, acinar cells underwent morphological and molecular changes indicative of ADM. mRNA from 14 donors' paired cells (day 0, acinar phenotype and day 6, ductal phenotype) was subjected to whole transcriptome sequencing. Acinar cell specific genes were significantly downregulated in the samples from the day 6 cultures while ductal cell-specific genes were upregulated. Several regulons of ADM were identified including transcription factors with reduced activity (PTF1A, RBPJL, and BHLHA15) and those ductal and progenitor transcription factors with increased activity (HNF1B, SOX11, and SOX4). Cells with the ductal phenotype contained higher expression of genes increased in pancreatic cancer while cells with an acinar phenotype had lower expression of cancer-associated genes. CONCLUSION: Our findings support the relevancy of human in vitro models to study pancreas cancer pathogenesis and exocrine cell plasticity.

Association of nativity with survival among adults with hepatocellular carcinoma.

INTRODUCTION: Immigrants comprise a considerable proportion of those diagnosed with hepatocellular carcinoma (HCC) in the United States. Nativity or birthplace affects incidence and risk factors for HCC, but little is known about its influence on survival after diagnosis. METHODS: We identified 51 533 adults with HCC with available birthplace in the California Cancer Registry between 1988 and 2017. HCC cases were categorized as foreign born or US born and stratified by mutually exclusive race and ethnicity groups. Primary outcome was all-cause mortality. Race and ethnicity-specific Cox regression propensity score-weighted models evaluated the relationship between nativity and death as well as region of birth among foreign-born patients. RESULTS: A total of 40% of all HCC cases were foreign born, and 92.2%, 45.2%, 9.1%, and 5.8% of Asian/Pacific Islander (API), Hispanic, White, and Black patients were foreign born, respectively. Five-year survival rates were higher in foreign-born patients compared with US-born patients: 12.9% vs 9.6% for White patients, 11.7% vs 9.8% for Hispanic patients, 12.8% vs 8.1% for Black patients, and 16.4% vs 12.4% for API patients. Nativity was associated with survival, with better survival in foreign-born patients: White patients: hazard ratio (HR) = 0.86 (95% confidence interval [CI] = 0.81 to 0.90), Hispanic patients: HR = 0.90 (95% CI = 0.86 to 0.93), Black patients: HR = 0.89 (95% CI = 0.76 to 1.05), and API patients: HR = 0.94 (95% CI = 0.88 to 1.00). Among foreign-born patients, lower mortality was observed in those from Central and South America compared with Mexico for Hispanic patients, East Asia compared with Southeast Asia for API patients, and East Europe and Greater Middle East compared with West/South/North Europe for White patients. CONCLUSION: Foreign-born patients with HCC have better survival than US-born patients. Further investigation into the mechanisms of this survival disparity by nativity is needed.

Population-attributable risk of modifiable lifestyle factors to hepatocellular carcinoma: The multi-ethnic cohort.

BACKGROUND AND AIMS: Lifestyle factors are well associated with risk of hepatocellular carcinoma (HCC). However, the impact of reducing adverse lifestyle behaviours on population-level burden of HCC is uncertain. METHODS: We conducted prospective analysis of the population-based multi-ethnic cohort (MEC) with linkage to cancer registries. The association of lifestyle factors (smoking, alcohol, diet quality assessed by alternate Mediterranean diet score, coffee drinking, physical activity and body mass index) with HCC incidence was examined using Cox regression. Population-attributable risk (PAR, %) for the overall, lean and overweight/obese populations was determined. RESULTS: A total of 753 incident cases of HCC were identified in 181,346 participants over median follow-up of 23.1 years. Lifestyle factors associated with elevated HCC risk included former/current smoking, heavy alcohol use, poor diet quality, lower coffee intake and obesity, but not physical activity. The lifestyle factor with highest PAR was lower coffee intake (21.3%; 95% CI: 8.9%-33.0%), followed by current smoking (15.1%; 11.1%-19.0%), obesity (14.5%; 9.2%-19.8%), heavy alcohol use (7.1%; 3.5%-10.6%) and lower diet quality (4.1%; 0.1%-8.1%). The combined PAR of all high-risk lifestyle factors was 51.9% (95% CI: 30.1%-68.6%). A higher combined PAR was observed among lean (65.2%, 26.8%-85.7%) compared to overweight/obese (37.4%, 11.7%-58.3%) participants. Adjusting for viral hepatitis status in a linked MEC-Medicare dataset resulted in similar PAR results. CONCLUSIONS: Modifying lifestyle factors, particularly coffee intake, may have a substantial impact on HCC burden in diverse populations, with greater impact among lean adults. Diet and lifestyle counselling should be incorporated into HCC prevention strategies.

Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort.

BACKGROUND: Certain dietary patterns (i.e., low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with the risk of gastric cancer. However, it is unclear whether overall diet quality assessed by predefined indices that consider the complexity of dietary intake is associated with gastric cardia and distal adenocarcinoma. OBJECTIVES: To examine the association of a variety of diet indices with the risk of gastric cardia and distal adenocarcinoma and assess whether there are any subgroups that may benefit from better diets to reduce the risk of gastric adenocarcinoma. METHODS: Dietary indices of interest included the Alternative Healthy Index (AHEI)-2010, Healthy Eating Index (HEI)-2015, the Dietary Approach to Stop Hypertension, alternate Mediterranean diet (aMED), and the energy-adjusted Dietary Inflammatory Index. RESULTS: After an average follow-up time of 19.2 years, there were 836 incident cases of gastric distal adenocarcinoma and 207 cases of gastric cardia adenocarcinoma. We did not observe any significant associations between the dietary indices and gastric cancer for either anatomic site. Among former aspirin users, we observed an inverse association between aMED with distal cancer (HRQ5 vs. Q1: 0.64; 95% CI: 0.33, 1.23; P-trend = 0.03). Never smokers, who showed high-quality diet according to AHEI-2010, exhibited a 40% decreased risk of gastric distal cancer compared with those with the poorest-quality AHEI-2010 diet (HRQ5 vs. Q1: 0.60; 95% CI: 0.41, 0.88; P-trend = 0.08). CONCLUSIONS: In a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among former aspirin users and never smokers, there could be a reduction of gastric distal adenocarcinoma risk with a higher adherence to a Mediterranean diet.

Race Differences in the Associations between Menstrual Cycle Characteristics and Epithelial Ovarian Cancer.

BACKGROUND: Menstrual cycle characteristics-including age at menarche and cycle length- have been associated with ovarian cancer risk in White women. However, the associations between menstrual cycle characteristics and ovarian cancer risk among Black women have been sparsely studied. METHODS: Using the Ovarian Cancer in Women of African Ancestry (OCWAA) Consortium that includes 1,024 Black and 2,910 White women diagnosed with epithelial ovarian cancer (EOC) and 2,325 Black and 7,549 White matched controls, we investigated associations between menstrual cycle characteristics (age at menarche, age at menstrual regularity, cycle length, and ever missing three periods) and EOC risk by race and menopausal status. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Black women were more likely to be <11 years at menarche than White women (controls: 9.9% vs. 6.0%). Compared with ≥15 years at menarche, <11 years was associated with increased EOC risk for White (OR = 1.25; 95% CI, 0.99-1.57) but not Black women (OR = 1.10; 95% CI, 0.80-1.55). Among White women only, the association was greater for premenopausal (OR = 2.20; 95% CI, 1.31-3.68) than postmenopausal women (OR = 1.06; 95% CI, 0.82-1.38). Irregular cycle length was inversely associated with risk for White (OR = 0.78; 95% CI, 0.62-0.99) but not Black women (OR = 1.06; 95% CI, 0.68-1.66). CONCLUSIONS: Earlier age at menarche and cycle irregularity are associated with increased EOC risk for White but not Black women. IMPACT: Associations between menstrual cycle characteristics and EOC risk were not uniform by race.

Prognostic utility of self-reported sarcopenia (SARC-F) in the Multiethnic Cohort.

BACKGROUND: Age-related loss in skeletal muscle mass, quality, and strength, known as sarcopenia, is a well-known phenomenon of aging and is determined clinically using methods such as dual-energy X-ray absorptiometry (DXA). However, these clinical methods to measure sarcopenia are not practical for population-based studies, and a five-question screening tool known as SARC-F has been validated to screen for sarcopenia. METHODS: We investigated the relationship between appendicular skeletal lean mass/height2 (ALM/HT2 ) (kg/m2 ) assessed by DXA and SARC-F in a subset of 1538 (778 men and 760 women) participants in the Multiethnic Cohort (MEC) Study after adjustment for race/ethnicity, age, and body mass index (BMI) at the time of DXA measurement. We then investigated the association between SARC-F and mortality among 71 283 (41 757 women and 29 526 men) participants in the MEC, who responded to the five SARC-F questions on a mailed questionnaire as part of the MEC follow-up in 2012-2016. RESULTS: In women, SARC-F score was significantly inversely associated with ALM/HT2 after adjusting for race/ethnicity, and age and BMI at DXA (r = -0.167, P < 0.001); the result was similar in men although it did not reach statistical significance (r = -0.056, P = 0.12). Among the 71 000+ MEC participants, SARC-F score ≥ 4, as an indicator of sarcopenia, was higher in women (20.9%) than in men (11.2%) (P < 0.0001) and increased steadily with increasing age (6.3% in <70 vs. 41.3% in 90+ years old) (P < 0.0001). SARC-F score ≥ 4 was highest among Latinos (30.8% in women and 16.1% in men) and lowest in Native Hawaiian women (15.6%) and Japanese American men (8.9%). During an average of 6.8 years of follow-up, compared with men with SARC-F score of 0-1 (indicator of no sarcopenia), men with SARC-F 2-3 (indicator of pre-sarcopenia) and SARC-F ≥ 4 had significantly increased risk of all-cause mortality [hazard ratio (HR) = 1.00, 1.77, 3.73, P < 0.001], cardiovascular disease (CVD) mortality (HR = 1.00, 1.85, 3.98, P < 0.001), and cancer mortality (HR = 1.00, 1.46, 1.96, P < 0.001) after covariate adjustment. Comparable risk association patterns with SARC-F scores were observed in women (all-cause mortality: HR = 1.00, 1.47, 3.10, P < 0.001; CVD mortality: HR = 1.00, 1.59, 3.54, P < 0.001; cancer mortality: HR = 1.00, 1.30, 1.77, P < 0.001). These significant risk patterns between SARC-F and all-cause mortality were found across all sex-race/ethnic groups considered (12 in total). CONCLUSIONS: An indicator of sarcopenia, determined using SARC-F, showed internal validity against DXA and displayed racial/ethnic and sex differences in distribution. SARC-F was associated with all-cause mortality as well as cause-specific mortality.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Racial/ethnic differences in postmenopausal breast cancer risk by hormone receptor status: The multiethnic cohort study.

There are racial/ethnic differences in the incidence of hormone receptor positive and negative breast cancer. To understand why these differences exist, we investigated associations between hormone-related factors and breast cancer risk by race/ethnicity in the Multiethnic Cohort (MEC) Study. Among 81 511 MEC participants (Native Hawaiian, Japanese American, Latina, African American and White women), 3806 estrogen receptor positive (ER+) and 828 ER- incident invasive breast cancers were diagnosed during a median of 21 years of follow-up. We used Cox proportional hazards regression models to calculate associations between race/ethnicity and breast cancer risk, and associations between hormone-related factors and breast cancer risk by race/ethnicity. Relative to White women, ER+ breast cancer risk was higher in Native Hawaiians and lower in Latinas and African Americans; ER- disease risk was higher in African Americans. We observed interaction with race/ethnicity in associations between oral contraceptive use (OC; Pint .03) and body mass index (BMI; Pint .05) with ER+ disease risk; ever versus never OC use increased risk only in Latinas and positive associations for obese versus lean BMI were strongest in Japanese Americans. For ER- disease risk, associations for OC use, particularly duration of use, were strongest for African Americans (Pint .04). Our study shows that associations of OC use and obesity with ER+ and ER- breast cancer risk differ by race/ethnicity, but established risk factors do not fully explain racial/ethnic differences in risk. Further studies are needed to identify factors to explain observed racial/ethnic differences in breast cancer incidence.

Diverging Incidence Trends for Hepatocellular Carcinoma in Rural and Urban Settings in the United States.

In the United States, hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related deaths and was the 5th most common cause in 2020.1 One in 5 Americans lives in a rural area,2 yet little is known about temporal changes in HCC incidence by rural-urban residence. Area-specific data are critical to guide public health strategies and clinical interventions. Our study compared the overall and subgroup incidence trends for HCC across rural and urban communities in the United States over the past 20 years using the North American Association of Central Cancer Registries database, which covers 93% of the United States and well-represents the rural United States (North American Association of Central Cancer Registries 14.6% rural vs United States 14.8% rural).3.

Racial/ethnic differences in anthropometric and hormone-related factors and endometrial cancer risk: the Multiethnic Cohort Study.

BACKGROUND: Anthropometric and hormone-related factors are established endometrial cancer risk factors; however, little is known about the impact of these factors on endometrial cancer risk in non-White women. METHODS: Among 110,712 women participating in the Multiethnic Cohort (MEC) Study, 1150 incident invasive endometrial cancers were diagnosed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with endometrial cancer risk for race/ethnicity and for risk factors across racial/ethnic groups were calculated. RESULTS: Having a higher body mass index (BMI) at baseline or age 21 years was strongly associated with increased risk (pint race/ethnicity ≥ 0.36). Parity (vs nulliparity) was inversely associated with risk in all the groups except African Americans (pint 0.006). Current use of postmenopausal hormones at baseline (PMH-E; vs never use) was associated with increased risk in Whites and Japanese Americans (pint 0.002). Relative to Whites, endometrial cancer risk was lower in Japanese Americans and Latinas and non-significantly higher in Native Hawaiians. Risk in African Americans did not differ from that in Whites. CONCLUSIONS: Racial/ethnic differences in endometrial cancer risk were not fully explained by anthropometric or hormone-related risk factors. Further studies are needed to identify reasons for the observed racial/ethnic differences in endometrial cancer risk.

Racial Differences in Population Attributable Risk for Epithelial Ovarian Cancer in the OCWAA Consortium.

BACKGROUND: The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women. METHODS: We used data from 4 case-control studies and 3 case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of 10 known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were 2-sided. RESULTS: Among 3244 White EOC cases and 9638 controls and 1052 AA EOC cases and 2410 controls, AA women had a statistically significantly higher PAR (false discovery rate [FDR] P < .001) for first-degree family history of breast cancer (PAR = 10.1%, 95% confidence interval [CI] = 6.5% to 13.7%) compared with White women (PAR = 2.6%, 95% CI = 0.8% to 4.4%). After multiple test correction, AA women had a higher PAR than White women when evaluating all risk factors collectively (PAR = 61.6%, 95% CI = 48.6% to 71.3% vs PAR = 43.0%, 95% CI = 32.8% to 51.4%, respectively; FDR P = .06) and for modifiable exposures, including body mass index, oral contraceptives, aspirin, and body powder (PAR = 36.0%, 95% CI = 21.0% to 48.8% vs PAR = 13.8%, 95% CI = 4.5% to 21.8%, respectively; FDR P = .04). CONCLUSIONS: Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC.

Racial/Ethnic Differences in Ovarian Cancer Risk: Results from the Multiethnic Cohort Study.

BACKGROUND: Incidence rates of epithelial ovarian cancer (EOC) vary across racial/ethnic groups, yet little is known about the impact of hormone-related EOC risk factors in non-Whites. METHODS: Among 91,625 female Multiethnic Cohort Study participants, 155 incident EOC cases were diagnosed in Whites, 93 in African Americans, 57 in Native Hawaiians, 161 in Japanese Americans, and 141 in Latinas. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between race/ethnicity and EOC risk and between hormone-related factors and EOC risk across racial/ethnic groups. RESULTS: Compared with Whites, African Americans and Japanese Americans had a lower multivariable-adjusted EOC risk; Native Hawaiians had a suggestive higher risk. Parity and oral contraceptive (OC) use were inversely associated with EOC risk (P int race/ethnicity ≥ 0.43); associations were strongest among Japanese Americans (e.g., ≥4 vs. 0 children; HR = 0.45; CI, 0.26-0.79). Age at natural menopause and postmenopausal hormone (PMH) use were not associated with EOC risk in the overall population, but were positively associated with risk in Latinas (e.g., ≥5 years vs. never PMH use; HR = 2.13; CI, 1.30-3.49). CONCLUSIONS: We observed strong associations with EOC risk for parity and OC use in Japanese Americans and PMH use and age at natural menopause in Latinas. However, differences in EOC risk among racial/ethnic groups were not fully explained by established hormone-related risk factors. IMPACT: Our study indicates there are racial/ethnic differences in EOC risk and risk factors, and could help improve prevention strategies for non-White women.

Increased hepatic and circulating chemokine and osteopontin expression occurs early in human NAFLD development.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma, is characterized by hepatic inflammation. Despite evolving therapies aimed to ameliorate inflammation in NASH, the transcriptional changes that lead to inflammation progression in NAFLD remain poorly understood. The aim of this pilot study was to define transcriptional changes in early, non-fibrotic NAFLD using two independent biopsy-proven NAFLD cohorts. METHODS: We extracted RNA from liver tissue of 40 patients with biopsy-proven NAFLD based on NAFLD Activity Score (NAS) (23 patients with NAS ≤3, 17 with NAS ≥5) and 21 healthy controls, and we compared changes in expression of 594 genes involved in innate immune function. Using plasma from an independent cohort of 67 patients with NAFLD and 15 healthy controls, we validated the gene changes observed using a multiplex protein assay. RESULTS: Compared to healthy controls, NAFLD patients with NAS ≥5 had differential expression of 211 genes, while those with NAS ≤3 had differential expression of only 14 genes. Notably, osteopontin (SPP1) (3.74-fold in NAS ≤3, 8.28-fold in NAS ≥5) and CXCL10 (2.27-fold in NAS ≤3, 8.28-fold in NAS ≥5) gene expression were significantly upregulated with histologic progression of NAFLD. Plasma osteopontin (SPP1) and CXCL10 are significantly increased in the presence of NAFLD, regardless of histologic grade. In addition, the plasma levels of these two proteins distinguish clearly between the presence or absence of NAFLD (AUC>0.90). CONCLUSIONS: Osteopontin (SPP1) and CXCL10 are upregulated early in non-fibrotic NAFLD and may serve as valuable non-invasive biomarkers.

Enhancing African American Participation in Biospecimens: A Case in Point for Pancreatic Cancer.

Diseases of the pancreas (i.e. chronic pancreatitis, diabetes, and pancreatic cancer) disproportionally affect the African American community. Challenges associated with engaging the African American community in biospecimen research are longstanding. We surveyed a number of pancreas-related biobanks, and data repositories for African American representation. While some of the biobanks and databases surveyed contain biospecimens and data from African American donors at levels that reflect minority representation among the general population, others do not. A number of factors have historically contributed to reduced participation of the African Americans community in biospecimen donation including medical mistrust, lack of transparency, fear, and a poor knowledge and understanding about the use of biospecimens for research. Suggestions for increasing African American participation in organ and biospecimen donation include educational interventions, particularly in community groups, and providing printed and online recruitment materials to patients, patient advocates, and care partners. Increasing awareness of the many benefits of biospecimen donation among African Americans will positively affect health disparities research into pancreatic cancer and other diseases.

Analgesic Use and Ovarian Cancer Risk: An Analysis in the Ovarian Cancer Cohort Consortium.

BACKGROUND: Aspirin use is associated with reduced risk of several cancers. A pooled analysis of 12 case-control studies showed a 10% decrease in ovarian cancer risk with regular aspirin use, which was stronger for daily and low-dose users. To prospectively investigate associations of analgesic use with ovarian cancer, we analyzed data from 13 studies in the Ovarian Cancer Cohort Consortium (OC3). METHODS: The current study included 758 829 women who at study enrollment self-reported analgesic use, among whom 3514 developed ovarian cancer. Using Cox regression, we assessed associations between frequent medication use and risk of ovarian cancer. Dose and duration were also evaluated. All statistical tests were two-sided. RESULTS: Women who used aspirin almost daily (≥6 days/wk) vs infrequent/nonuse experienced a 10% reduction in ovarian cancer risk (rate ratio [RR] = 0.90, 95% confidence interval [CI] = 0.82 to 1.00, P = .05). Frequent use (≥4 days/wk) of aspirin (RR = 0.95, 95% CI = 0.88 to 1.03), nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs; RR = 1.00, 95% CI = 0.90 to 1.11), or acetaminophen (RR = 1.05, 95% CI = 0.88 to 1.24) was not associated with risk. Daily acetaminophen use (RR = 1.28, 95% CI = 1.00 to 1.65, P = .05) was associated with elevated ovarian cancer risk. Risk estimates for frequent, long-term (10+ years) use of aspirin (RR = 1.15, 95% CI = 0.98 to 1.34) or nonaspirin NSAIDs (RR = 1.19, 95% CI = 0.84 to 1.68) were modestly elevated, although not statistically significantly so. CONCLUSIONS: This large, prospective analysis suggests that women who use aspirin daily have a slightly lower risk of developing ovarian cancer (∼10% lower than infrequent/nonuse)-similar to the risk reduction observed in case-control analyses. The observed potential elevated risks for 10+ years of frequent aspirin and NSAID use require further study but could be due to confounding by medical indications for use or variation in drug dosing.