Dietary isoflavone intake is not statistically significantly associated with breast cancer risk in the Multiethnic Cohort

Given the high intake levels of soya and low incidence rates of breast cancer in Asian countries, isoflavones, substances with an oestrogen-like structure occurring principally in soyabeans, are postulated to be cancer protective. In the present study, we examined the association of dietary isoflavone intake with breast cancer risk in 84 450 women (896 in situ and 3873 invasive cases) who were part of the Multiethnic Cohort (Japanese Americans, whites, Latinos, African Americans and Native Hawaiians) with a wide range of soya intake levels. The absolute levels of dietary isoflavone intake estimated from a baseline FFQ were categorised into quartiles, with the highest quartile being further subdivided to assess high dietary intake. The respective intake values for the quartiles (Q1, Q2, Q3, and lower and upper Q4) were 0– < 3·2, 3·2– < 6·7, 6·7– < 12·9, 12·9– < 20·3, and 20·3–178·7 mg/d. After a mean follow-up period of 13 years, hazard ratios (HR) and 95 % CI were calculated using Cox regression models stratified by age and adjusted for known confounders. Linear trends were tested by modelling continuous variables of interest assigned the median value within the corresponding quartile. No statistically significant association was observed between dietary isoflavone intake and overall breast cancer risk (HR for upper Q4 v. Q1: 0·96 (95 % CI 0·85, 1·08); P trend = 0·40). While the test for interaction was not significant (P= 0·14), stratified analyses suggested possible ethnic/racial differences in risk estimates, indicating that higher isoflavone intakes may be protective in Latina, African American and Japanese American women. These results are in agreement with those of previous meta-analyses showing no protection of isoflavones at low intake levels, but suggesting inverse associations in populations consuming high amounts of soya.

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Plasma sex hormone concentrations and breast cancer risk in an ethnically diverse population of postmenopausal women: the Multiethnic Cohort Study

Endocrine Related Cancer ◽

10.1677/erc-09-0211 ◽

2010 ◽

Vol 17 (1) ◽

pp. 125-134 ◽

Cited By ~ 44

Author(s):

Christy G Woolcott ◽

Yurii B Shvetsov ◽

Frank Z Stanczyk ◽

Lynne R Wilkens ◽

Kami K White ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Postmenopausal Women ◽

Sex Hormones ◽

Ethnically Diverse ◽

Sex Hormone ◽

Japanese American ◽

Diverse Population ◽

Multiethnic Cohort

To add to the existing evidence that comes mostly from White populations, we conducted a nested case–control study to examine the association between sex hormones and breast cancer risk within the Multiethnic Cohort that includes Japanese American, White, Native Hawaiian, African American, and Latina women. Of the postmenopausal women for whom we had a plasma sample, 132 developed breast cancer during follow-up. Two controls per case, matched on study area (Hawaii, Los Angeles), ethnicity/race, birth year, date and time of blood draw and time fasting, were randomly selected from the women who had not developed breast cancer. Levels of estradiol (E2), estrone (E1), androstenedione, dehydroepiandrosterone (DHEA), and testosterone were quantified by RIA after organic extraction and Celite column partition chromatography. E1 sulfate, DHEA sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were quantified by direct immunoassays. Based on conditional logistic regression, the sex hormones were positively associated and SHBG was negatively associated with breast cancer risk. All associations, except those with DHEAS and testosterone showed a significant linear trend. The odds ratio (OR) associated with a doubling of E2 levels was 2.26 (95% confidence interval (CI) 1.58–3.25), and the OR associated with a doubling of testosterone levels was 1.34 (95% CI 0.98–1.82). The associations in Japanese American women, who constituted 54% of our sample, were similar to or nonsignificantly stronger than in the overall group. This study provides the best evidence to date that the association between sex hormones and breast cancer risk is generalizable to an ethnically diverse population.

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Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

British Journal of Cancer ◽

10.1038/s41416-021-01392-z ◽

2021 ◽

Author(s):

Sandar Tin Tin ◽

Gillian K. Reeves ◽

Timothy J. Key

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Invasive Breast Cancer ◽

Cox Regression ◽

Menopausal Status ◽

Endogenous Hormones ◽

Uk Biobank ◽

Menopausal Women ◽

Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

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IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort

British Journal of Cancer ◽

10.1038/sj.bjc.6600728 ◽

2003 ◽

Vol 88 (2) ◽

pp. 277-282 ◽

Cited By ~ 65

Author(s):

K DeLellis ◽

S Ingles ◽

L Kolonel ◽

R McKean-Cowdin ◽

B Henderson ◽

...

Keyword(s):

Breast Cancer ◽

Los Angeles ◽

Breast Cancer Risk ◽

Plasma Level ◽

Cancer Risk ◽

Multiethnic Cohort

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Physical Activity and Risk of Type 2 Diabetes Among Native Hawaiians, Japanese Americans, and Caucasians: The Multiethnic Cohort

Journal of Physical Activity and Health ◽

10.1123/jpah.9.5.634 ◽

2012 ◽

Vol 9 (5) ◽

pp. 634-641 ◽

Cited By ~ 19

Author(s):

Astrid Steinbrecher ◽

Eva Erber ◽

Andrew Grandinetti ◽

Claudio Nigg ◽

Laurence N. Kolonel ◽

...

Keyword(s):

Physical Activity ◽

Ethnic Groups ◽

Cox Regression ◽

Diabetes Risk ◽

Self Report ◽

Japanese Americans ◽

Japanese American ◽

Moderate Activity ◽

Inverse Association ◽

Multiethnic Cohort

Background:Physical inactivity is an established risk factor for diabetes; however, little is known about this association across ethnic groups with different diabetes risk. Therefore, we evaluated the association between physical activity and diabetes and potential effect modification by ethnicity in the Hawaii component of the Multiethnic Cohort.Methods:Participants, aged 45 to 75 years, were enrolled by completing a questionnaire on demographics, diet, and self-reported weekly hours of strenuous sports, vigorous work, and moderate activity. Among the 74,913 participants (39% Caucasian, 14% Native Hawaiian, 47% Japanese American), 8561 incident diabetes cases were identified by self-report, a medication questionnaire, and through health plan linkages. Cox regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) while adjusting for known confounders.Results:Engaging in strenuous sports was inversely related to diabetes risk with HRs (4+ hours/week vs. never) of 0.67 (95%CI: 0.57–0.79) in women and 0.80 (95%CI: 0.72–0.88) in men. In stratified analyses, the inverse association was consistent across ethnic groups. The inverse association of vigorous work with diabetes was limited to men, while beneficial effects of moderate activity were observed only in Caucasians.Conclusions:These findings support a role of high-intensity physical activity and ethnic-specific guidelines in diabetes prevention.

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Racial/Ethnic Differences in Lung Cancer Incidence in the Multiethnic Cohort Study: An Update

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djy206 ◽

2019 ◽

Vol 111 (8) ◽

pp. 811-819 ◽

Cited By ~ 18

Author(s):

Daniel O Stram ◽

S Lani Park ◽

Christopher A Haiman ◽

Sharon E Murphy ◽

Yesha Patel ◽

...

Keyword(s):

Lung Cancer ◽

Cohort Study ◽

African Americans ◽

Cancer Risk ◽

Racial Differences ◽

Lung Cancer Risk ◽

Native Hawaiians ◽

Japanese Americans ◽

Urinary Biomarker ◽

Multiethnic Cohort

Abstract Background We previously found that African Americans and Native Hawaiians were at highest lung cancer risk compared with Japanese Americans and Latinos; whites were midway in risk. These differences were more evident at relatively low levels of smoking intensity, fewer than 20 cigarettes per day (CPD), than at higher intensity. Methods We apportioned lung cancer risk into three parts: age-specific background risk (among never smokers), an excess relative risk term for cumulative smoking, and modifiers of the smoking effect: race and years-quit smoking. We also explored the effect of replacing self-reports of CPD with a urinary biomarker—total nicotine equivalents—using data from a urinary biomarker substudy. Results Total lung cancers increased from 1979 to 4993 compared to earlier analysis. Estimated excess relative risks for lung cancer due to smoking for 50 years at 10 CPD (25 pack-years) ranged from 21.9 (95% CI = 18.0 to 25.8) for Native Hawaiians to 8.0 (95% CI = 6.6 to 9.4) for Latinos over the five groups. The risk from smoking was higher for squamous cell carcinomas and small cell cancers than for adenocarcinomas. Racial differences consistent with earlier patterns were seen for overall cancer and for cancer subtypes. Adjusting for predicted total nicotine equivalents, Japanese Americans no longer exhibit a lower risk, and African Americans are no longer at higher risk, compared to whites. Striking risk differences between Native Hawaiians and Latinos persist. Conclusions Racial differences in lung cancer risk persist in the Multiethnic Cohort study that are not easily explained by variations in self-reported or urinary biomarker-measured smoking intensities.

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Methylation-Based Biological Age and Breast Cancer Risk

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djz020 ◽

2019 ◽

Vol 111 (10) ◽

pp. 1051-1058 ◽

Cited By ~ 34

Author(s):

Jacob K Kresovich ◽

Zongli Xu ◽

Katie M O’Brien ◽

Clarice R Weinberg ◽

Dale P Sandler ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cox Regression ◽

Disease Risk ◽

Statistical Tests ◽

Biological Age ◽

Cancer Case ◽

Increased Risk

Abstract Background Age is one of the strongest predictors of cancer, chronic disease, and mortality, but biological responses to aging differ among people. Epigenetic DNA modifications have been used to estimate “biological age,” which may be a useful predictor of disease risk. We tested this hypothesis for breast cancer. Methods Using a case-cohort approach, we measured baseline blood DNA methylation of 2764 women enrolled in the Sister Study, 1566 of whom subsequently developed breast cancer after an average of 6 years. Using three previously established methylation-based “clocks” (Hannum, Horvath, and Levine), we defined biological age acceleration for each woman by comparing her estimated biological age with her chronological age. Hazard ratios and 95% confidence intervals for breast cancer risk were estimated using Cox regression models. All statistical tests were two-sided. Results Each of the three clocks showed that biological age acceleration was statistically significantly associated with increased risk of developing breast cancer (5-year age acceleration, Hannum’s clock: hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.00 to 1.21, P = .04; Horvath’s clock: HR = 1.08, 95% CI = 1.00 to 1.17, P = .04; Levine’s clock: HR = 1.15, 95% CI = 1.07 to 1.23, P < .001). For Levine’s clock, each 5-year acceleration in biological age corresponded with a 15% increase in breast cancer risk. Although biological age may accelerate with menopausal transition, age acceleration in premenopausal women independently predicted breast cancer. Case-only analysis suggested that, among women who develop breast cancer, increased age acceleration is associated with invasive cancer (odds ratio for invasive = 1.09, 95% CI = 0.98 to 1.22, P = .10). Conclusions DNA methylation-based measures of biological age may be important predictors of breast cancer risk.

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Binge Drinking and Risk of Breast Cancer: Results from the SUN (‘Seguimiento Universidad de Navarra’) Project

Nutrients ◽

10.3390/nu12030731 ◽

2020 ◽

Vol 12 (3) ◽

pp. 731

Author(s):

Rodrigo Sánchez-Bayona ◽

Alfredo Gea ◽

Itziar Gardeazabal ◽

Andrea Romanos-Nanclares ◽

Miguel Ángel Martínez-González ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Binge Drinking ◽

Cox Regression ◽

Menopausal Status ◽

The Sun ◽

Stratified Analysis ◽

Incident Cases

Alcohol intake is associated with the risk of breast cancer. Different patterns of alcohol-drinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03–2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11–3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.

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Cirrus: An Automated Mammography-Based Measure of Breast Cancer Risk Based on Textural Features

JNCI Cancer Spectrum ◽

10.1093/jncics/pky057 ◽

2018 ◽

Vol 2 (4) ◽

Cited By ~ 6

Author(s):

Daniel F Schmidt ◽

Enes Makalic ◽

Benjamin Goudey ◽

Gillian S Dite ◽

Jennifer Stone ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Mammographic Density ◽

Risk Measure ◽

Case Control ◽

Image Features ◽

Japanese American ◽

Textural Features ◽

Lasso Regression

Abstract Background We applied machine learning to find a novel breast cancer predictor based on information in a mammogram. Methods Using image-processing techniques, we automatically processed 46 158 analog mammograms for 1345 cases and 4235 controls from a cohort and case–control study of Australian women, and a cohort study of Japanese American women, extracting 20 textural features not based on pixel brightness threshold. We used Bayesian lasso regression to create individual- and mammogram-specific measures of breast cancer risk, Cirrus. We trained and tested measures across studies. We fitted Cirrus with conventional mammographic density measures using logistic regression, and computed odds ratios (OR) per standard deviation adjusted for age and body mass index. Results Combining studies, almost all textural features were associated with case–control status. The ORs for Cirrus measures trained on one study and tested on another study ranged from 1.56 to 1.78 (all P < 10−6). For the Cirrus measure derived from combining studies, the OR was 1.90 (95% confidence interval [CI] = 1.73 to 2.09), equivalent to a fourfold interquartile risk ratio, and was little attenuated after adjusting for conventional measures. In contrast, the OR for the conventional measure was 1.34 (95% CI = 1.25 to 1.43), and after adjusting for Cirrus it became 1.16 (95% CI = 1.08 to 1.24; P = 4 × 10−5). Conclusions A fully automated personal risk measure created from combining textural image features performs better at predicting breast cancer risk than conventional mammographic density risk measures, capturing half the risk-predicting ability of the latter measures. In terms of differentiating affected and unaffected women on a population basis, Cirrus could be one of the strongest known risk factors for breast cancer.

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Physical activity and breast cancer risk: results from the UK Biobank prospective cohort

British Journal of Cancer ◽

10.1038/s41416-019-0700-6 ◽

2020 ◽

Vol 122 (5) ◽

pp. 726-732 ◽

Cited By ~ 6

Author(s):

Wenji Guo ◽

Georgina K. Fensom ◽

Gillian K. Reeves ◽

Timothy J. Key

Keyword(s):

Breast Cancer ◽

Physical Activity ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cox Regression ◽

Postmenopausal Breast Cancer ◽

Protective Role ◽

Accelerometer Data ◽

Uk Biobank ◽

Relative Risks

Abstract Background Previous studies suggest a protective role of physical activity in breast cancer risk, largely based on self-reported activity. We aimed to clarify this association by examining breast cancer risk in relation to self-reported physical activity, informed by accelerometer-based measures in a large subset of participants. Methods We analysed data from 47,456 premenopausal and 126,704 postmenopausal women in UK Biobank followed from 2006 to 2014. Physical activity was self-reported at baseline, and at resurvey in a subsample of 6443 participants. Accelerometer data, measured from 2013 to 2015, were available in 20,785 women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using multivariable-adjusted Cox regression. Results A total of 3189 cases were diagnosed during follow-up (mean = 5.7 years). Women in the top compared with the bottom quartile of self-reported physical activity had a reduced risk of both premenopausal (RR 0.75; 95% CI 0.60–0.93) and postmenopausal breast cancer (RR 0.87; 95% CI 0.78–0.98), after adjusting for adiposity. In analyses utilising physical activity values assigned from accelerometer measurements, an increase of 5 milli-gravity was associated with a 21% (RR 0.79; 95% CI 0.66–0.95) reduction in premenopausal and a 16% (RR 0.84; 95% CI 0.73–0.96) reduction in postmenopausal breast cancer risk. Conclusions Greater physical activity is associated with a reduction in breast cancer risk, which appears to be independent of any association it may have on risk through its effects on adiposity.

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