Prospective data on ethnic differences in hormone receptor-defined subtypes of breast cancer and their risk factor profiles are scarce. The authors examined the joint distributions of estrogen ...receptor (ER) and progesterone receptor (PR) status across 5 ethnic groups and the associations of established risk factors with ER/PR status in the Multiethnic Cohort Study (Hawaii and Los Angeles, California). During an average of 10.4 years of follow-up of 84,427 women between 1993–1996 and 2004/2005, 2,543 breast cancer cases with data on ER/PR status were identified: 1,672 estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+); 303 ER+/progesterone receptor-negative (PR−); 77 estrogen receptor-negative (ER−)/PR+; and 491 ER−/PR−. ER/PR status varied significantly across racial/ethnic groups even within the same tumor stage (for localized tumors, P < 0.0001; for advanced tumors, P = 0.01). The highest fraction of ER−/PR− tumors was observed in African Americans (31%), followed by Latinas (25%), Whites (18%), Japanese (14%), and Native Hawaiians (14%). Associations differed between ER+/PR+ and ER−/PR− cases for postmenopausal obesity (P = 0.02), age at menarche (P = 0.05), age at first birth (P = 0.04), and postmenopausal hormone use (P < 0.0001). African Americans are more likely to be diagnosed with ER−/PR− tumors independently of stage at diagnosis, and there are disparate risk factor profiles across the ER/PR subtypes of breast cancer.
We prospectively examined the association between smoking and the risk of breast cancer in a racially/ethnically diverse population comprising mainly women who did not drink alcohol. From 1993 to ...2010, we followed 83,300 women who were enrolled in the Multiethnic Cohort Study at 45-75 years of age. We identified cancer cases via linkage to the Surveillance, Epidemiology, and End Results Program cancer registries that covered the states of Hawaii and California through December 2010. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals while adjusting for confounders that were decided a priori. During a mean follow-up of 15 years, 4,484 women developed invasive breast cancer. Compared with parous never smokers, women who had smoked for more than 20 pack-years and initiated smoking more than 5 years before their first childbirth had an overall risk of breast cancer that was 35% higher (hazard ratio = 1.35, 95% confidence interval: 1.13, 1.63). Among women who did not drink alcohol, the risk was 40% higher (hazard ratio = 1.40, 95% confidence interval: 1.08, 1.81). This higher risk did not significantly differ among racial/ethnic groups (P(interaction) = 0.82). We found that various measures of smoking exposure were associated with a higher risk of breast cancer, especially smoking initiated many years before first childbirth, and that risk did not differ by alcohol consumption (yes vs. no) or racial/ethnic group.
The association of body size, lifestyle, and medical conditions with renal cell cancer risk was examined among 161,126 Hawaii–Los Angeles Multiethnic Cohort participants (1993–2002). After 8.3 years ...of follow-up, 347 renal cell cancer cases (220 men, 127 women) were identified. Renal cell cancer risk increased with increasing body mass index in men (multivariate relative risk (RR) = 1.06 per unit of body mass index, p = 0.001) and women (RR = 1.07, p < 0.0001). The relative risks associated with being obese compared with being lean were 1.76 (95% confidence interval (CI): 1.20, 2.58) for men and 2.27 (95% CI: 1.37, 3.74) for women. Hypertension was associated with renal cell cancer (RRmen = 1.42, 95% CI: 1.07, 1.87; RRwomen = 1.58, 95% CI: 1.09, 2.28). Smoking was confirmed to be a risk factor for both sexes. Among women, diuretic use was associated with increased risk (RR = 1.63, 95% CI: 1.04, 2.57), whereas physical activity was associated with reduced risk (ptrend = 0.027). Alcohol consumption was inversely associated with risk for men (ptrend = 0.045). Compared with nondrinkers, men who drank ≥1 drinks/day had a 31% lower risk (95% CI: 0.49, 0.96). Results show that body mass index, smoking, and hypertension are risk factors for renal cell cancer in both sexes.
Breast cancer survival has been found to be lower in obese women, but few studies have evaluated ethnic variations in this association. This study examined all-cause and breast cancer-specific ...survival by body mass index (BMI) in the Multiethnic Cohort (MEC) study for African American, Native Hawaiian, Japanese American, Latino, and Caucasian women. Female MEC participants free of breast cancer, aged ≥50 years at cohort entry, and diagnosed with primary invasive breast cancer during follow-up were included in the analyses (
n
= 3,842). Cox proportional hazards regression was used to estimate the effect of pre-diagnostic adult BMI (<22.5, 22.5–24.9, 25.0–29.9, ≥30 kg/m
2
) on the risk of mortality. Mean age at diagnosis was 68.8 years (range 50–89 years). During a mean follow-up of 6.2 ± 3.8 years after diagnosis, there were 804 deaths that included 376 breast cancer-specific deaths. After adjustment for breast cancer characteristics, including hormone receptor status, stage at diagnosis, and treatment, obese women had a higher risk of all-cause hazard ratio (HR) = 1.54; 95% confidence interval (CI): 1.23, 1.91 and breast cancer-specific (HR = 1.45; 95% CI: 1.05, 2.00) mortality compared to women with high-normal BMI; however, being overweight did not affect survival. There was no evidence of ethnic differences in the BMI effect on all-cause (
P
interaction
= 0.87) or breast cancer-specific (
P
interaction
= 0.63) mortality. Our findings are consistent with the literature that maintaining moderate weight throughout adult life may be beneficial for breast cancer survival in women and this appears to hold for all ethnic groups.
Characterization of abdominal and intra-abdominal fat requires imaging, and thus is not feasible in large epidemiologic studies.
We investigated whether biomarkers may complement anthropometry (body ...mass index BMI, waist circumference WC, and waist-hip ratio WHR) in predicting the size of the body fat compartments by analyzing blood biomarkers, including adipocytokines, insulin resistance markers, sex steroid hormones, lipids, liver enzymes and gastro-neuropeptides.
Fasting levels of 58 blood markers were analyzed in 60 healthy, Caucasian or Japanese American postmenopausal women who underwent anthropometric measurements, dual energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging. Total, abdominal, visceral and hepatic adiposity were predicted based on anthropometry and the biomarkers using Random Forest models.
Total body fat was well predicted by anthropometry alone (R(2) = 0.85), by the 5 best predictors from the biomarker model alone (leptin, leptin-adiponectin ratio LAR, free estradiol, plasminogen activator inhibitor-1 PAI1, alanine transaminase ALT; R(2) = 0.69), or by combining these 5 biomarkers with anthropometry (R(2) = 0.91). Abdominal adiposity (DXA trunk-to-periphery fat ratio) was better predicted by combining the two types of predictors (R(2) = 0.58) than by anthropometry alone (R(2) = 0.53) or the 5 best biomarkers alone (25(OH)-vitamin D(3), insulin-like growth factor binding protein-1 IGFBP1, uric acid, soluble leptin receptor sLEPR, Coenzyme Q10; R(2) = 0.35). Similarly, visceral fat was slightly better predicted by combining the predictors (R(2) = 0.68) than by anthropometry alone (R(2) = 0.65) or the 5 best biomarker predictors alone (leptin, C-reactive protein CRP, LAR, lycopene, vitamin D(3); R(2) = 0.58). Percent liver fat was predicted better by the 5 best biomarker predictors (insulin, sex hormone binding globulin SHBG, LAR, alpha-tocopherol, PAI1; R(2) = 0.42) or by combining the predictors (R(2) = 0.44) than by anthropometry alone (R(2) = 0.29).
The predictive ability of anthropometry for body fat distribution may be enhanced by measuring a small number of biomarkers. Studies to replicate these data in men and other ethnic groups are warranted.
We have previously reported multiple loci associated with prostate cancer susceptibility in a Japanese population using a genome-wide association study (GWAS). To identify additional prostate cancer ...susceptibility loci, we genotyped nine SNPs that were nominally associated with prostate cancer (P < 1 × 10(-4)) in our previous GWAS in three independent studies of prostate cancer in Japanese men (2,557 individuals with prostate cancer (cases) and 3,003 controls). In a meta-analysis of our previous GWAS and the replication studies, which included a total of 7,141 prostate cancer cases and 11,804 controls from a single ancestry group, three new loci reached genome-wide significance on chromosomes 11q12 (rs1938781; P = 1.10 × 10(-10); FAM111A-FAM111B), 10q26 (rs2252004; P = 1.98 × 10(-8)) and 3p11.2 (rs2055109; P = 3.94 × 10(-8)). We also found suggestive evidence of association at a previously reported prostate cancer susceptibility locus at 2p11 (rs2028898; P = 1.08 × 10(-7)). The identification of three new susceptibility loci should provide additional insight into the pathogenesis of prostate cancer and emphasizes the importance of conducting GWAS in diverse populations.
Recent oral contraceptive (OC) use has been consistently associated with increased risk of breast cancer, but evidence on specific breast cancer subtypes is sparse.
We investigated recency and ...duration of OC use in relation to molecular subtypes of breast cancer in a pooled analysis of data from the African American Breast Cancer Epidemiology and Risk Consortium. The study included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043 with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors, which do not have receptors for estrogen, progesterone, and human epidermal growth factor 2), and 10,044 controls. Multivariable polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for exposure categories relative to never use, controlling for potential confounding variables.
OC use within the previous 5 years was associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR 1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer. The risk declined after cessation of use but was apparent for ER+ cancer for 15 to 19 years after cessation and for ER- breast cancer for an even longer interval after cessation. Long duration of use was also associated with increased risk of each subtype, particularly ER-.
Our results suggest that OC use, particularly recent use of long duration, is associated with an increased risk of ER+, ER-, and TN breast cancer in African American women. Research into mechanisms that explain these findings, especially the association with ER- breast cancer, is needed.
OBJECTIVETo examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS).
METHODSWe identified 275 individuals who developed ...ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS.
RESULTSThere was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartileRR = 0.21 95% CI 0.07, 0.58, p for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartileRR = 1.65 95% CI 0.99, 2.76, p for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartileRR = 1.56 95% CI 1.01, 2.41, p for trend = 0.054), but in multivariable models the association was only evident in men.
CONCLUSIONSThe majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies.
Incidence rates in the United States show clear racial/ethnic disparities for colorectal cancer. We examined the extent to which ethnic differences in risk factors could explain the age‐adjusted ...variation in the risk of colorectal cancer, overall and by stage at diagnosis, among 165,711 African Americans, Japanese Americans, Latinos, Native Hawaiians and whites participating in the Multiethnic Cohort Study. Over a median follow‐up period of 10.7 years, 2,564 incident cases of colorectal cancer were identified through surveillance, epidemiology and end result tumor registry linkages in Hawaii and California. Multivariable‐adjusted Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for each ethnic group compared to whites. After accounting for known/suspected risk factors, Japanese Americans (men, RR = 1.27, 95% CI = 1.09–1.48; women, RR = 1.49, 95% CI = 1.24–1.78) and African American women (RR = 1.48, 95% CI = 1.23–1.79) remained at increased risk of colorectal cancer relative to whites; African American and Japanese American women were also at increased risk of advanced disease compared to whites. In site‐specific analyses, after multivariable adjustment, African Americans (both sexes) and Japanese American women remained at increased risk for colon cancer, and Japanese Americans (both sexes) and Native Hawaiian men for rectal cancer compared to whites. The results of our study suggest that differences in the distribution of known/suspected risk factors account for only a modest proportion of the ethnic variation in colorectal cancer risk and that other factors, possibly including genetic susceptibility, are important contributors to the observed disparities in incidence.
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