Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium.

BACKGROUND: Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander (NHPI) women. METHODS: Participants included 1734 Asian (785 cases, 949 controls), 266 NHPI (99 cases, 167 controls), 1149 Hispanic (505 cases, 644 controls), and 24,189 White (9,981 cases, 14,208 controls) women from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations by race and ethnicity. RESULTS: Heterogeneity in EOC risk associations by race and ethnicity (p ≤ 0.02) was observed for oral contraceptive (OC) use, parity, tubal ligation and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in NHPI and Asian women. The inverse association for tubal ligation with risk was most pronounced for NHPI participants (OR=0.25, 95% CI 0.13-0.48), versus Asian and White participants, respectively (OR=0.68, 95% CI 0.51-0.90; OR=0.78, 95% CI 0.73-0.85). CONCLUSIONS: Differences in EOC risk factor associations were observed across racial and ethnic groups, which could in part be due to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies.

Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies.

BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: There were 842 149 men followed for up to 9 to 22 years between 1985 and 2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), and high-grade PC (Gleason score ≥8 or poorly differentiated/undifferentiated) and PC mortality. STATISTICAL ANALYSIS PERFORMED: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% CI 0.76-0.93), advanced restricted PC (MVHR 0.85; 95% CI 0.74-0.97), and PC mortality (MVHR 0.78; 95% CI 0.68-0.89); statistically significant trends were noted for each of these associations (P ≤ .03), and a null association was observed for high-grade PC for the same comparison (MVHR 1.00; 95% CI 0.93-1.07). The comparable results were 1.06 (95% CI 1.01-1.10; P value, test for trend = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366). CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high-grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.

No Association of Trichomonas vaginalis Seropositivity with Advanced Prostate Cancer Risk in the Multiethnic Cohort: A Nested Case-Control Study.

The potential involvement of a sexually transmitted agent has been suggested to contribute to the high number of prostate cancers in the United States and worldwide. We investigated the relationship of Trichomonas vaginalis seropositivity with prostate cancer risk in a nested case-control study within the Multiethnic Cohort in Hawaii and California using blood samples collected prior to cancer diagnoses. Incident cases of advanced prostate cancer (intermediate- to high-grade based on Gleason score ≥ 7 and/or disease spread outside the prostate) were matched to controls by age, ethnicity, and the date of blood collection. T. vaginalis serostatus was measured using an ELISA detecting IgG antibodies against a recombinant T. vaginalis α-actinin protein. Seropositivity to T. vaginalis was observed in 35 of 470 (7.4%) cases and 26 of 470 (5.5%) controls (unadjusted OR = 1.47, 95% CI 0.82-2.64; adjusted OR = 1.31, 95% CI 0.67-2.53). The association was similarly not significant when cases were confined to extraprostatic tumors having regional or distant spread (n = 121) regardless of grade (unadjusted OR = 1.37, 95% CI 0.63-3.01; adjusted OR = 1.20, 95% CI 0.46-3.11). The association of T. vaginalis with prostate cancer risk did not vary by aspirin use. Our findings do not support a role for T. vaginalis in the etiology of advanced prostate cancer.

Circulating 27-hydroxycholesterol, lipids, and steroid hormones in breast cancer risk: a nested case-control study of the Multiethnic Cohort Study.

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.

The impact of COVID-19 on cancer screening and treatment in older adults: The Multiethnic Cohort Study.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Funding: This research was partially supported by the Omidyar 'Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.

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.

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.

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.

Prediction of breast cancer risk among women of the Mariana Islands: the BRISK retrospective case-control study.

OBJECTIVES: To develop a breast cancer risk prediction model for Chamorro and Filipino women of the Mariana Islands and compare its performance to that of the Breast Cancer Risk Assessment Tool (BCRAT). DESIGN: Case-control study. SETTING: Clinics/facilities and other community-based settings on Guam and Saipan (Northern Mariana Islands). PARTICIPANTS: 245 women (87 breast cancer cases and 158 controls) of Chamorro or Filipino ethnicity, age 25-80 years, with no prior history of cancer (other than skin cancer), residing on Guam or Saipan for at least 5 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Breast cancer risk models were constructed using combinations of exposures previously identified to affect breast cancer risk in this population, population breast cancer incidence rates and all-cause mortality rates for Guam. RESULTS: Models using ethnic-specific relative risks performed better than those with relative risks estimated from all women. The model with the best performance among both ethnicities (the Breast Cancer Risk Model (BRISK) model; area under the receiver operating characteristic curve (AUC): 0.64 and 0.67 among Chamorros and Filipinos, respectively) included age at menarche, age at first live birth, number of relatives with breast cancer and waist circumference. The 10-year breast cancer risk predicted by the BRISK model was 1.28% for Chamorros and 0.89% for Filipinos. Performance of the BCRAT was modest among both Chamorros (AUC: 0.60) and Filipinos (AUC: 0.55), possibly due to incomplete information on BCRAT risk factors. CONCLUSIONS: The ability to develop breast cancer risk models for Mariana Islands women is constrained by the small population size and limited availability of health services and data. Nonetheless, we have demonstrated that breast cancer risk prediction models with adequate discriminatory performance can be built for small populations such as in the Mariana Islands. Anthropometry, in particular waist circumference, was important for estimating breast cancer risk in this population.

Weight changes according to treatment in a diverse cohort of breast cancer patients.

BACKGROUND: Weight changes are common among breast cancer patients. The majority of studies to date have focused on weight gain after a breast cancer diagnosis and its implications on health in survivors. Fewer studies have examined weight loss and its related characteristics. Weight changes have been reported to be influenced by several factors such as age, treatment, stage and pre-diagnostic weight. We evaluated weight changes during key treatment time points in early stage breast cancer patients. METHODS: We characterized 389 female patients diagnosed in Hawaii with early stage breast cancer from 2003 to 2017 in the Multiethnic Cohort (MEC) linked with Kaiser Permanente Hawaii electronic medical record data. We evaluated weight changes from surgery to 4 years post-diagnosis with six time points along a patient's treatment trajectory (chemotherapy, radiation, endocrine, or surgery alone) and annually thereafter, adjusting for age, race/ethnicity and initial body mass index (BMI). RESULTS: We found key time points of significant weight change for breast cancer patients according to their adjuvant treatment. In patients who had surgery alone (S), surgery-radiation (SR), or surgery-endocrine therapy (SE), the majority of patients had stable weight, although this consistently decreased over time. However, the percentages of patients with weight loss and weight gain during this time steadily increased up to 4 years after initial surgery. Weight loss was more common than weight gain by about 2 fold in these treatment groups. For patients with surgery-chemotherapy (SC), there was significant weight loss seen within the first 3 months after surgery, during the time when patients receive chemotherapy. And this weight loss persisted until year 4. Weight gain was less commonly seen in this treatment group. CONCLUSIONS: We identified key time points during breast cancer treatment that may provide a therapeutic window to positively influence outcomes. Tailored weight management interventions should be utilized to promote overall health and long term survivorship.

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.

Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status: a pooled analysis of 20 prospective cohort studies.

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.

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.

Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts.

BACKGROUND: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. METHODS: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. RESULTS: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. CONCLUSIONS: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

Mediators of a 12-month change in physical activity in ethnically diverse sample of postpartum women.

PURPOSE: Understanding theoretically derived social and behavioral mediators of long-term increases in physical activity (PA) in a vulnerable population at risk for being underactive is needed to inform future research, clinical applications, and public health efforts. This is an analysis of potential mediators of an intervention that increased long-term (12-month) moderate-to-vigorous physical activity (MVPA) in postpartum (2-12months) women in a randomized trial, using a longitudinal analysis. METHODS: Healthy, underactive (i.e., not meeting national guidelines for MVPA) women (n = 311; mean age = 32 ± 5.6 years, 85% minorities) with infants (mean age: 5.7 ± 2.8 months) were randomly assigned to either a tailored eHealth condition consisting of personalized telephone counseling plus access to a website tailored to new mothers' MVPA issues or to a standard MVPA materials-only website. MVPA was assessed via surveys completed at baseline, then 6 and 12 months later. Theoretically derived mediators included social support for MVPA, self-efficacy to increase MVPA, barriers to increasing MVPA, and benefits of increasing MVPA. RESULTS: All mediators, except benefits, improved over the 12 months in the tailored eHealth condition. The tailored condition's effect on increasing MVPA from 6 months to 12 months was mediated by an increase in social support from baseline to six months. No other hypothesized mediators were significant. CONCLUSION: Our results demonstrated that learning strategies to increase social support for MVPA was instrumental in new mothers' increase in MVPA over a 12 month intervention. During this brief but impactful life-stage, where the focus can understandably be on her baby, being able to elicit support from friends and family may facilitate women's efforts to focus on their own needs with respect to MVPA. TRIAL REGISTRATION: ClinicalTrials.gov number.

Biomonitoring an albumin adduct of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in humans.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed in cooked meats and may be linked to dietary-associated colorectal, prostate and mammary cancers. Genotoxic N-oxidized metabolites of PhIP react with the Cys34 of albumin (Alb) to form a sulfinamide adduct, a biomarker of the biologically effective dose. We examined the kinetics of PhIP-Alb adduct formation in plasma of volunteers on a 4-week semicontrolled diet of cooked meat containing known quantities of PhIP. The adduct was below the limit of detection (LOD) (10 femtograms PhIP/mg Alb) in most subjects before the meat feeding but increased by up to 560-fold at week 4 in subjects who ate meat containing 8.0 to 11.7 µg of PhIP per 150-200 g serving. In contrast, the adduct remained below the LOD in subjects who ingested 1.2 or 3.0 µg PhIP per serving. Correlations were not seen between PhIP-Alb adduct levels and PhIP intake levels (P = 0.76), the amount of PhIP accrued in hair (P = 0.13), the amounts of N-oxidized urinary metabolites of PhIP (P = 0.66) or caffeine CYP1A2 activity (P = 0.55), a key enzyme involved in the bioactivation of PhIP. The half-life of the PhIP-Alb adduct was <2 weeks, signifying that the adduct was not stable. PhIP-Alb adduct formation is direct evidence of bioactivation of PhIP in vivo. However, the PhIP hair biomarker is a longer lived and more sensitive biomarker to assess exposure to this potential human carcinogen.

Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan.

BACKGROUND: Chamorro Pacific Islanders in the Mariana Islands have breast cancer incidence rates similar to, but mortality rates higher than, those of U.S. women. As breast cancer risk factors of women of the Mariana Islands may be unique because of ethnic and cultural differences, we studied established and suspected risk factors for breast cancer in this unstudied population. METHODS: From 2010-2013, we conducted retrospective case-control study of female breast cancer (104 cases and 185 controls) among women in the Mariana Islands. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of various lifestyle-related factors from logistic regression of breast cancer, in all women and in pre- and postmenopausal women separately. Tests for interaction of risk factors with ethnicity were based on the Wald statistics for cross-product terms. RESULTS: Of the medical and reproductive factors considered - age at menarche, breastfeeding, number of live births, age at first live birth, hormone use, and menopause - only age at first live birth was confirmed. Age at first live birth, among parous women, was higher among cases (mean 24.9 years) than controls (mean 23.2 years); with increased breast cancer risk (OR=2.53; 95% CI, 1.04-6.19 for age≥30y compared to <20y, P for trend=0.01). Of the lifestyle factors -body mass index, waist circumference, physical activity, alcohol and betel-nut intake, and education - only waist circumference (OR=1.65; 95% CI 0.87-3.14 for the highest tertile group compared to the lowest, P for trend=0.04) was significantly associated with breast cancer risk and only in Filipino women. The association with many other established risk factors, such as BMI, hormone use and physical activity, were in the expected direction but were not significant. Associations for family history of breast cancer and alcohol intake were not evident CONCLUSIONS: The results provide a basis for cancer prevention guidance for women in the Mariana Islands.

Dose validation of PhIP hair level as a biomarker of heterocyclic aromatic amines exposure: a feeding study.

Hair measurement of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a promising biomarker of exposure to this carcinogen formed in cooked meats. However, the dose relationship between normal range intake and hair levels and the modulating effects of CYP1A2 metabolism and hair melanin need to be evaluated. We conducted a randomized, cross-over feeding study among 41 non-smokers using ground beef cooked to two different levels of doneness, 5 days a week for 1 month. PhIP was measured by liquid chromatography/mass spectrometry in food (mean low dose = 0.72 µg/serving; mean high dose = 2.99 µg/serving), and change in PhIP hair level was evaluated. CYP1A2 activity was assessed in urine with the caffeine challenge test and head hair melanin was estimated by UV spectrophotometry. We observed a strong dose-dependent increase in hair PhIP levels. This increase was highly correlated with dose received (ρ = 0.68, P < 0.0001). CYP1A2 activity and normalizing for hair melanin did not modify the response to the intervention. Consumption of PhIP at doses similar to those in the American diet results in a marked dose-dependent accumulation of PhIP in hair. Hair PhIP levels may be used as a biomarker of dietary exposure in studies investigating disease risk.

Caffeine Cytochrome P450 1A2 Metabolic Phenotype Does Not Predict the Metabolism of Heterocyclic Aromatic Amines in Humans.

2-Amino-1-methylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are carcinogenic heterocyclic aromatic amines (HAAs) formed in well-done cooked meats. Chemicals that induce cytochrome P450 (P450) 1A2, a major enzyme involved in the bioactivation of HAAs, also form in cooked meat. Therefore, well-done cooked meat may pose an increase in cancer risk because it contains both inducers of P450 1A2 and procarcinogenic HAAs. We examined the influence of components in meat to modulate P450 1A2 activity and the metabolism of PhIP and MeIQx in volunteers during a 4 week feeding study of well-done cooked beef. The mean P450 1A2 activity, assessed by caffeine metabolic phenotyping, ranged from 6.3 to 7.1 before the feeding study commenced and from 9.6 to 10.4 during the meat feeding period: the difference in means was significant (P < 0.001). Unaltered PhIP, MeIQx, and their P450 1A2 metabolites, N(2)-(ß-1-glucosiduronyl)-2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (HON-PhIP-N(2)-Gl); N3-(ß-1-glucosiduronyl)-2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (HON-PhIP-N3-Gl); 2-amino-3-methylimidazo-[4,5-f]quinoxaline-8-carboxylic acid (IQx-8-COOH); and 2-amino-8-(hydroxymethyl)-3-methylimidazo[4,5-f]quinoxaline (8-CH2OH-IQx) were measured in urine during days 2, 14, and 28 of the meat diet. Significant correlations were observed on these days between the levels of the unaltered HAAs and their oxidized metabolites, when expressed as percent of dose ingested or as metabolic ratios. However, there was no statistically significant correlation between the caffeine P450 1A2 phenotype and any urinary HAA biomarker. Although the P450 1A2 activity varied by greater than 20-fold among the subjects, there was a large intraindividual variation of the P450 1A2 phenotype and inconsistent responses to inducers of P450 1A2. The coefficient of variation of the P450 1A2 phenotype within-individual ranged between 1 to 112% (median = 40%) during the entire course of the study. The caffeine metabolic phenotype for P450 1A2 was a poor predictor of oxidative urinary metabolites of PhIP and MeIQx and may not be a reliable measure to assess the role of HAAs in cancer risk.