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.

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.

Risk of Alzheimer's disease and related dementia by sex and race/ethnicity: The Multiethnic Cohort Study.

INTRODUCTION: Data are limited for comparison of sex- and race/ethnicity-specific risks of Alzheimer's disease and related dementia (ADRD). METHODS: In the population-based Multiethnic Cohort, we estimated the age-standardized diagnostic incidence rate (ASDIR) and relative risk of late-onset ADRD (n = 16,410) among 105,796 participants based on Medicare claims (1999-2014) by sex and race/ethnicity. RESULTS: The ASDIR for ADRD was higher for women (17.0 per 1000 person-years) than for men (15.3) and varied across African Americans (22.9 in women, 21.5 in men), Native Hawaiians (19.3, 19.4), Latinos (16.8, 14.7), Whites (16.4, 15.5), Japanese Americans (14.8, 13.8), and Filipinos (12.5, 9.7). Similar risk patterns were observed for AD. Adjustment for education and cardiometabolic diseases attenuated the differences. Accounting for deaths from competing causes increased the sex difference, while reducing the racial/ethnic differences. Less racial/ethnic disparity was detected among apolipoprotein E (APOE) e4 carriers. DISCUSSION: More research is needed to understand the sex and racial/ethnic differences in ADRD.

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.

Long-term association between diet quality and characteristics of the gut microbiome in the multiethnic cohort study.

As past usual diet quality may affect gut microbiome (GM) composition, we examined the association of the Healthy Eating Index (HEI)-2015 assessed 21 and 9 years before stool collection with measures of fecal microbial composition in a subset of the Multiethnic Cohort. A total of 5936 participants completed a validated quantitative FFQ (QFFQ) at cohort entry (Q1, 1993-1996), 5280 at follow-up (Q3, 2003-2008) and 1685 also at a second follow-up (Adiposity Phenotype Study (APS), 2013-2016). All participants provided a stool sample in 2013-2016. Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1-V3 regions). HEI-2015 scores were computed based on each QFFQ. Using linear regression adjusted for relevant covariates, we calculated associations of HEI-2015 scores with gut microbial diversity and 152 individual genera. The mean HEI-2015 scores increased from Q1 (67 (sd 10)) to Q3 (71 (sd 11)) and APS (72 (sd 10)). Alpha diversity assessed by the Shannon Index was significantly higher with increasing tertiles of HEI-2015. Of the 152 bacterial genera tested, seven (Anaerostipes, Coprococcus_2, Eubacterium eligens, Lachnospira, Lachnospiraceae_ND3007, Ruminococcaceae_UCG-013 and Ruminococcus_1) were positively and five (Collinsella, Parabacteroides, Ruminiclostridium_5, Ruminococcus gnavus and Tyzzerella) were inversely associated with HEI-2015 assessed in Q1, Q3 and APS. The estimates of change per unit of the HEI-2015 score associated with the abundance of these twelve genera were consistent across the three questionnaires. The quality of past diet, assessed as far as ∼20 years before stool collection, is equally predictive of GM composition as concurrently assessed diet, indicative of the long-term consistency of this relation.

Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium.

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.

Risk factors for endometrial cancer in black and white women: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2).

PURPOSE: Endometrial cancer (EC) is the most common gynecologic cancer in the USA. Over the last decade, the incidence rate has been increasing, with a larger increase among blacks. The aim of this study was to compare risk factors for EC in black and white women. METHODS: Data from seven cohort and four case-control studies were pooled. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95 % confidence intervals for each risk factor in blacks and whites separately. RESULTS: Data were pooled for 2,011 black women (516 cases and 1,495 controls) and 19,297 white women (5,693 cases and 13,604 controls). BMI ≥ 30 was associated with an approximate threefold increase in risk of EC in both black and white women (ORblack 2.93, 95 % CI 2.11, 4.07 and ORwhite 2.99, 95 % CI 2.74, 3.26). Diabetes was associated with a 30-40 % increase in risk among both groups. Increasing parity was associated with decreasing risk of EC in blacks and whites (p value = 0.02 and <0.001, respectively). Current and former smoking was associated with decreased risk of EC among all women. Both black and white women who used oral contraceptives for 10 +years were also at reduced risk of EC (OR 0.49, 95 % CI 0.27, 0.88 and OR 0.69, 95 % CI 0.58, 0.83, respectively). Previous history of hypertension was not associated with EC risk in either group. CONCLUSIONS: The major known risk factors for EC exert similar effects on black and white women. Differences in the incidence rates between the two populations may be due to differences in the prevalence of risk factors.

Impact of sex on the survival of patients with hepatocellular carcinoma: a Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: Men are 4 to 8 times more likely to develop hepatocellular carcinoma (HCC) than women. Preclinical models have suggested a role for sex hormones in the development of HCC. In the current study, the authors investigated the impact of age, sex, race, and ethnicity on the survival of patients with HCC using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with HCC from 1988 through 2010 were identified from the SEER registry. Hazard ratios (HR) for overall survival (OS) were derived using the Cox regression model adjusted for race, year of diagnosis, marital status, treatment, birthplace, tumor differentiation, and tumor size. RESULTS: A total of 39,345 patients were identified; 76% were men and 34% were women (50% white, 12% African American, 21% Asian, 16% Hispanic, and 1% Native American). The median age at the time of diagnosis was 61 years for men and 67 years for women. Approximately 84% of patients had liver-limited disease and 16% had metastatic disease. Treatment information was available for patients diagnosed after 1998 (34,674 patients): 11% received liver-directed therapy, 11% underwent surgical resection, and 7% underwent liver transplantation. The HR for the OS of women versus men was 0.83 (95% confidence interval [95% CI], 0.77-0.88) for patients aged <55 years. The protective effect of sex on OS was found to be greatest in patients aged 18 to 44 years (HR, 0.75; 95% CI, 0.65-0.86 [P<.001]), especially those with surgically resected tumors (HR, 0.68; 95% CI, 0.54-0.86 [P = .001]) and those who were African American (HR, 0.85; 95% CI, 0.78-0.92 [P<.001]). There was no survival difference between sexes noted among Hispanics or patients aged >65 years. CONCLUSIONS: Sex appears to be associated with survival in patients with HCC. The role of androgens and estrogens in the development and progression of HCC warrants further investigation.

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.

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.

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.

Racial, Ethnic, and Socioeconomic Differences in a Deficit Accumulation Frailty Index in the Multiethnic Cohort Study.

BACKGROUND: Frailty status has been sparsely studied in some groups including Native Hawaiians and Asian Americans. METHODS: We developed a questionnaire-based deficit accumulation frailty index (FI) in the Multiethnic Cohort (MEC) and examined frailty status (robust, FI 0 to <0.2, prefrail, FI 0.2 to <0.35, and frail FI ≥ 0.35) among 29 026 men and 40 756 women. RESULTS: After adjustment for age, demographic, lifestyle factors, and chronic conditions, relative to White men, odds of being frail was significantly higher (34%-54%) among African American, Native Hawaiian, and other Asian American men, whereas odds was significantly lower (36%) in Japanese American men and did not differ in Latino men. However, among men who had high school or less, none of the groups displayed significantly higher odds of prefrail or frail compared with White men. Relative to White women, odds of being frail were significantly higher (14%-33%) in African American and Latino women, did not differ for other Asian American women and lower (14%-36%) in Native Hawaiian and Japanese American women. These racial and ethnic differences in women were observed irrespective of education. Risk of all-cause mortality was higher in prefrail and frail men than robust men (adjusted hazard ratio [HR] = 1.69, 1.59-1.81; HR = 3.27, 3.03-3.53); results were similar in women. All-cause mortality was significantly positively associated with frailty status and frailty score across all sex, race, and ethnic groups. CONCLUSIONS: Frailty status differed significantly by race and ethnicity and was consistently associated with all-cause mortality. The FI may be a useful tool for aging studies in this multiethnic population.

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 Habitual Intake of Probiotic Supplements and Yogurt with Characteristics of the Gut Microbiome in the Multiethnic Cohort Adiposity Phenotype Study.

Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60-72 years). Fecal microbial composition was obtained from 16S rRNA gene sequencing (V1-V3 region). General Linear Models were used to estimate the associations of probiotic supplement or yogurt intake with microbiome measures adjusting for covariates. Compared to non-yogurt consumers (N=1,023), regular yogurt consumers (≥once/week, N=818) had greater Streptococcus (ß=0.29, P=0.0003) and lower Odoribacter (ß=-0.33, P<0.0001) abundance. The directions of the above associations were consistent across the five ethnic groups but stronger among Japanese Americans (Streptococcus: ß=0.56, P=0.0009; Odoribacter: ß=-0.62, P=0.0005). Regular intake of probiotic supplements (N=175) was not associated with microbial characteristics (i.e., alpha diversity and the abundance of 152 bacteria genera). Streptococcus is one of the predominant bacteria genera in yogurt products, which may explain the positive association between yogurt consumption and Streptococcus abundance. Our analyses suggest that changes in Odoribacter were independent of changes in Streptococcus abundance. Future studies may investigate whether these microbial genera and their sub-level species mediate potential pathways between yogurt consumption and health.

Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium.

There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P(trend) = 1.5 × 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.