Explore the vast range of titles available.

Self-identified race/ethnicity is a correlate of both genetic ancestry and socioeconomic factors, both of which may contribute to racial disparities in mortality. Investigators often hold a priori assumptions, rarely made explicit, regarding the relative importance of these factors. We studied 2,239 self-identified African Americans (SIAA) from the Prostate, Lung, Colorectal and Ovarian screening trial enrolled from 1993–1998 and followed prospectively until 2019 or until death, whichever came first. Percent African genetic ancestry was estimated using the GRAF-Pop distance-based method. A neighborhood socioeconomic status (nSES) index was estimated using census tract measures of income, housing, and employment and linked to participant residence in 2012. We used Directed Acyclic Graphs (DAGs) to represent causal models favoring (1) biomedical and (2) social causes of mortality. Hazard ratios were estimated using Cox models adjusted for sociodemographic, behavioral, and neighborhood covariates guided by each DAG. 901 deaths occurred over 40,767 person-years of follow-up. In unadjusted (biomedical) models, a 10% increase in percent African ancestry was associated with a 7% higher rate of all-cause mortality (HR: 1.07, 95% CI: 1.02, 1.12). This effect was attenuated in covariate adjusted (social) models (aHR: 1.01, 95% CI: 0.96, 1.06). Mortality was lower comparing participants in the highest to lowest nSES quintile following adjustment for covariates and ancestry (aHR: 0.74, 95% CI: 0.57, 0.98, P trend = 0.017). Higher African ancestry and lower nSES were associated with higher mortality, but African ancestry was not associated with mortality following covariate adjustment. Socioeconomic factors may be more important drivers of mortality in African Americans.

Purpose In contrast to other US racial/ethnic groups, Asian Americans (AA) have experienced steadily increasing breast cancer rates in recent decades. To better understand potential contributors to this increase, we examined incidence trends by age and stage among women from seven AA ethnic groups in California from 1988 to 2013, and incidence patterns by subtype and age at diagnosis for the years 2009 through 2013. Methods Joinpoint regression was applied to California Cancer Registry data to calculate annual percentage change (APC) for incidence trends. Incidence rate ratios were used to compare rates for AA ethnic groups relative to non-Hispanic whites (NHW). Results All AA groups except Japanese experienced incidence increases, with the largest among Koreans in 1988–2006 (APC 4.7, 95% CI 3.8, 5.7) and Southeast Asians in 1988–2013 (APC 2.5, 95% CI 0.8, 4.2). Among women younger than age 50, large increases occurred for Vietnamese and other Southeast Asians; among women over age 50, increasing trends occurred in all AA ethnic groups. Rates increased for distant-stage disease among Filipinas (2.2% per year, 95% CI 0.4, 3.9). Compared to NHW, Filipinas and older Vietnamese had higher incidence rates of some HER2+ subtypes. Conclusions Breast cancer incidence rates have risen rapidly among California AA, with the greatest increases in Koreans and Southeast Asians. Culturally tailored efforts to increase awareness of and attention to breast cancer risk factors are needed. Given the relatively higher rates of HER2-overexpressing subtypes in some AA ethnicities, research including these groups and their potentially unique exposures may help elucidate disease etiology.

Have you noticed that some people seem to get older faster than others? Scientists have previously found that a chemical tag on DNA known as DNA methylation can be used to predict an individual’s chronological age. However, age predicted using DNA methylation (also known as biological or epigenetic age) does not always perfectly correspond to chronological age. Indeed, some people’s biological age is higher than their years, while other people’s is lower. When an individual’s biological age is higher than their chronological age, they are said to be experiencing ‘epigenetic age acceleration’. This type of accelerated ageing, which can be measured with ‘epigenetic clocks’ based on DNA methylation, has been associated with several adverse health outcomes, including cancer. This means that epigenetic clocks may improve our ability to predict cancer risk and detect cancer early. However, it is still unclear whether accelerated biological ageing causes cancer, or whether it simply correlates with the disease. Morales-Berstein et al. wanted to investigate whether epigenetic age acceleration, as measured by epigenetic clocks, plays a role in the development of several cancers. To do so, they used an approach known as Mendelian randomization. Using genetic variants as natural experiments, they studied the effect of different measures of epigenetic age acceleration on cancer risk. Their work focused on five types of cancer: breast, colorectal, prostate, ovarian and lung cancer. They used genetic association data from people of European ancestry to determine whether genetic variants that are strongly associated with accelerated ageing are also strongly associated with cancer. The results showed that one of the DNA methylation markers used as an estimate of biological ageing could be directly related to the risk of developing colorectal cancer. This work provides new insights into the relationship between markers of biological ageing and cancer. Similar relationships should also be studied in other groups of people and for other cancer sites. The results suggest that reversing biological ageing by altering DNA methylation could prevent or delay the development of colorectal cancer.

Self-identified race/ethnicity is a correlate of both genetic ancestry and socioeconomic factors, both of which may contribute to racial disparities in mortality. Investigators often hold a priori assumptions, rarely made explicit, regarding the relative importance of these factors. We studied 2,239 self-identified African Americans (SIAA) from the Prostate, Lung, Colorectal and Ovarian screening trial enrolled from 1993-1998 and followed prospectively until 2019 or until death, whichever came first. Percent African genetic ancestry was estimated using the GRAF-Pop distance-based method. A neighborhood socioeconomic status (nSES) index was estimated using census tract measures of income, housing, and employment and linked to participant residence in 2012. We used Directed Acyclic Graphs (DAGs) to represent causal models favoring (1) biomedical and (2) social causes of mortality. Hazard ratios were estimated using Cox models adjusted for sociodemographic, behavioral, and neighborhood covariates guided by each DAG. 901 deaths occurred over 40,767 person-years of follow-up. In unadjusted (biomedical) models, a 10% increase in percent African ancestry was associated with a 7% higher rate of all-cause mortality (HR: 1.07, 95% CI: 1.02, 1.12). This effect was attenuated in covariate adjusted (social) models (aHR: 1.01, 95% CI: 0.96, 1.06). Mortality was lower comparing participants in the highest to lowest nSES quintile following adjustment for covariates and ancestry (aHR: 0.74, 95% CI: 0.57, 0.98, Ptrend = 0.017). Higher African ancestry and lower nSES were associated with higher mortality, but African ancestry was not associated with mortality following covariate adjustment. Socioeconomic factors may be more important drivers of mortality in African Americans.

Background The epidemiologic evidence from observational studies on breast cancer risk and phthalates, endocrine disrupting chemicals, has been inconsistent. In the only previous study based on pre-diagnostic urinary phthalates and risk of breast cancer, results were null in mostly white women. Methods We examined the association between pre-diagnostic urinary phthalates and breast cancer in a nested case-control study within the Multiethnic Cohort (MEC) study, presenting the first data from five major racial/ethnic groups in the USA. We measured 10 phthalate metabolites and phthalic acid, using a sensitive liquid chromatography mass spectrometry assay on 1032 women with breast cancer (48 African Americans, 77 Latinos, 155 Native Hawaiians, 478 Japanese Americans, and 274 Whites) and 1030 matched controls. Conditional logistic regression was used to examine risk with individual metabolites and ratios of primary (MEHP, mono-2-ethylhexyl-phthalate) to secondary (MEHHP, mono(2-ethyl-5-hydroxyhexyl); MEOHP, mono(2-ethyl-5-oxohexy)) metabolites of di-2-ethylhexyl phthalate (DEHP), a widely used plasticizer. In addition, we investigated risk associations with high (∑HMWP) and low molecular weight (∑LMWP) phthalates, as well as total phthalates which included high and low molecular weight phthalates with phthalic acid (∑LMHMPA) or without phthalic acid in molar ratios (∑LMHM molar ) and adjusted for creatinine and potential confounders. Results Among all women, breast cancer risk was higher for those in tertile 2 and tertile 3 of primary to secondary metabolites of DEHP (MEHP/(MEHHP + MEOHP)) in comparison to those in tertile 1; the respective odds ratios were 1.32 (95% CI 1.04–1.68) and 1.26 (95% CI 0.96–1.66) ( P trend  = 0.05). Risk among Native Hawaiian women increased with exposures to eight of ten individual phthalates and total phthalates (∑LMHMPA OR T3 vs T1  = 2.66, 95% CI 1.39–5.12, P trend  = 0.001). In analysis by hormone receptor (HR) status, exposure above the median of ∑LMWP was associated with an increased risk of HR-positive breast cancer (OR = 1.30, 95% CI 1.05–1.60) while above the median exposure to phthalic acid was associated with an increased risk of HR-negative breast cancer (OR above vs below median  = 1.59, 95% CI 1.01–2.48). Conclusions Further investigations of suggestive associations of elevated breast cancer risk with higher ratios of primary to secondary metabolites of DEHP, and differences in risk patterns by race/ethnicity and HR status are warranted.

Background Laboratory studies have indicated that a cholesterol metabolite and selective estrogen receptor modulator, 27-hydroxycholesterol (27HC), may be important in breast cancer etiology and explain associations between obesity and postmenopausal breast cancer risk. Epidemiologic evidence for 27HC in breast cancer risk is limited, particularly in multiethnic populations. Methods In a nested case–control study of 1470 breast cancer cases and 1470 matched controls within the Multiethnic Cohort Study, we examined associations of pre-diagnostic circulating 27HC with breast cancer risk among African American, Japanese American, Native Hawaiian, Latino, and non-Latino White postmenopausal females. We used multivariable logistic regression adjusted for age, education, parity, body mass index, and smoking status. Stratified analyses were conducted across racial and ethnic groups, hormone receptor (HR) status, and use of lipid-lowering drugs. We assessed interactions of 27HC with steroid hormones. Results 27HC levels were inversely related to breast cancer risk (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.58, 1.12), but the association was not statistically significant in the full model. Directions of associations differed by racial and ethnic group. Results suggested an inverse association with HR-negative breast cancer (OR 0.46; 95% CI 0.20, 1.06). 27HC interacted with testosterone, but not estrone, on risk of breast cancer; 27HC was only inversely associated with risk among those with the highest levels of testosterone (OR 0.46; 95% CI 0.24, 0.86). Conclusion This is the first US study to examine circulating 27HC and breast cancer risk and reports a weak inverse association that varies across racial and ethnic groups and testosterone level.

We previously developed a prediction score for MRI-quantified abdominal visceral adipose tissue (VAT) based on concurrent measurements of height, body mass index (BMI), and nine blood biomarkers, for optimal performance in five racial/ethnic groups. Here we evaluated the VAT score for prediction of future VAT and examined if enhancement with additional biomarkers, lifestyle behavior information, and medical history improves the prediction. We examined 500 participants from the Multiethnic Cohort (MEC) with detailed data (age 50-66) collected 10 years prior to their MRI assessment of VAT. We generated three forecasted VAT prediction models: first by applying the original VAT equation to the past data on the predictors (\"original\"), second by refitting the past data on anthropometry and biomarkers (\"refit\"), and third by building a new prediction model based on the past data enhanced with lifestyle and medical history (\"enhanced\"). We compared the forecasted prediction scores to future VAT using the coefficient of determination (R2). In independent nested case-control data in MEC, we applied the concurrent and forecasted VAT models to assess association of the scores with subsequent incident breast cancer (950 pairs) and colorectal cancer (831 pairs). Compared to the VAT prediction by the concurrent VAT score (R2 = 0.70 in men, 0.68 in women), the forecasted original VAT score (R2 = 0.54, 0.48) performed better than past anthropometry alone (R2 = 0.47, 0.40) or two published scores (VAI, METS-VF). The forecasted refit (R2 = 0.61, 0.51) and enhanced (R2 = 0.62, 0.55) VAT scores each showed slight improvements. Similar to the concurrent VAT score, the forecasted VAT scores were associated with breast cancer, but not colorectal cancer. Both the refit score (adjusted OR for tertile 3 vs. 1 = 1.27; 95% CI: 1.00-1.62) and enhanced score (1.27; 0.99-1.62) were associated with breast cancer independently of BMI. Predicted VAT from midlife data can be used as a surrogate to assess the effect of VAT on incident diseases associated with obesity, as illustrated for postmenopausal breast cancer.

Epidemiological studies of obesity, Type-2 diabetes (T2D), cardiovascular diseases and several common cancers have revealed an increased risk in Native Hawaiians compared to European- or Asian-Americans living in the Hawaiian islands. However, there remains a gap in our understanding of the genetic factors that affect the health of Native Hawaiians. To fill this gap, we studied the genetic risk factors at both the chromosomal and sub-chromosomal scales using genome-wide SNP array data on ~4,000 Native Hawaiians from the Multiethnic Cohort. We estimated the genomic proportion of Native Hawaiian ancestry (“global ancestry,” which we presumed to be Polynesian in origin), as well as this ancestral component along each chromosome (“local ancestry”) and tested their respective association with binary and quantitative cardiometabolic traits. After attempting to adjust for non-genetic covariates evaluated through questionnaires, we found that per 10% increase in global Polynesian genetic ancestry, there is a respective 8.6%, and 11.0% increase in the odds of being diabetic ( P = 1.65×10 −4 ) and having heart failure ( P = 2.18×10 −4 ), as well as a 0.059 s.d. increase in BMI ( P = 1.04×10 −10 ). When testing the association of local Polynesian ancestry with risk of disease or biomarkers, we identified a chr6 region associated with T2D. This association was driven by an uniquely prevalent variant in Polynesian ancestry individuals. However, we could not replicate this finding in an independent Polynesian cohort from Samoa due to the small sample size of the replication cohort. In conclusion, we showed that Polynesian ancestry, which likely capture both genetic and lifestyle risk factors, is associated with an increased risk of obesity, Type-2 diabetes, and heart failure, and that larger cohorts of Polynesian ancestry individuals will be needed to replicate the putative association on chr6 with T2D.

The Coronavirus Disease of 2019 (COVID-19) has impacted the health and day-to-day life of individuals, especially the elderly and people with certain pre-existing medical conditions, including cancer. The purpose of this study was to investigate how COVID-19 impacted access to cancer screenings and treatment, by studying the participants in the Multiethnic Cohort (MEC) study. The MEC has been following over 215,000 residents of Hawai'i and Los Angeles for the development of cancer and other chronic diseases since 1993-1996. It includes men and women of five racial and ethnic groups: African American, Japanese American, Latino, Native Hawaiian, and White. In 2020, surviving participants were sent an invitation to complete an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening and treatment. Approximately 7,000 MEC participants responded. A cross-sectional analysis was performed to investigate the relationships between the postponement of regular health care visits and cancer screening procedures or treatment with race and ethnicity, age, education, and comorbidity. Women with more education, women with lung disease, COPD, or asthma, and women and men diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Groups less likely to postpone cancer screening included older women compared to younger women and Japanese American men and women compared to White men and women. This study revealed specific associations of race/ethnicity, age, education level, and comorbidities with the cancer-related screening and healthcare of MEC participants during the COVID-19 pandemic. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis is increased as a result of delayed screening and treatment. This research was partially supported by the Omidyar 'Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.

Purpose: Older age, African ancestry, and family history of prostate cancer are well-established risk factors for prostate cancer, and all are non-modifiable. Various lifestyle factors have been examined in relation to prostate cancer risk, including diet, obesity, and physical activity; however, none of them has been consistently related to risk. In the Multiethnic Cohort Study, we investigated whether lifestyle-related factors are associated with prostate cancer risk and whether such factors explain the racial/ethnic differences in risk. Methods: During a mean follow-up of 13.9 years, 7,115 incident cases were identified among 75,216 white, African-American, Native Hawaiian, Japanese American, and Latino men. Cox proportional hazards models were used to calculate relative risks (RRs) and 95 % confidence intervals (95 % CIs) for prostate cancer. Results: Among selected lifestyle-related factors including body mass index, height, education, physical activity, and intakes of alcohol, calcium, legumes, lycopene, and selenium, only smoking (RR for current (≥20 cigarettes/day) vs. never smoking = 0.72; 95 % CI 0.63–0.83) and history of diabetes (RR for yes vs. no = 0.78; 95 % CI 0.72–0.85) were significantly associated with prostate cancer risk. Compared to whites, the risk of incident prostate cancer was twofold higher in African-Americans and 16 % higher in Latinos. Additional adjustment for a history of PSA testing did not change the results. Conclusions: The findings suggest that racial/ethnic differences in prostate cancer risk are not explained by the lifestyle factors examined and that underlying genetic factors may be involved.