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Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses' health studies.

ABSTRACT: High levels of circulating carotenoids are hypothesized to reduce breast cancer risk, potentially due to their antioxidant properties. However, little is known about the relationship between carotenoid exposure earlier in life and risk. We examined associations of premenopausal plasma carotenoids and markers of oxidative stress and risk of breast cancer among 1179 case-control pairs in the Nurses' Health Study (NHS) and NHSII. Levels of ?- and ?-carotene, ?-cryptoxanthin, lycopene, and lutein/zeaxanthin were quantified by high-performance liquid chromatography. Three fluorescent oxidation products (FlOP_360, FlOP_320, FlOP_400) were measured in a subset of participants by spectrofluoroscopy. Multivariate conditional logistic regression was used to estimate odds ratios and 95 % confidence intervals for breast cancer by quartile, as well as P values for tests of linear trend. We additionally examined whether 45 single-nucleotide polymorphisms (SNPs) in five genes involved in oxidative and antioxidative processes or carotenoid availability were associated with risk. Carotenoid measures were not inversely associated with breast cancer risk. No differences by estrogen receptor status were observed, though some inverse associations were observed among women postmenopausal at diagnosis. Plasma FlOP levels were not positively associated with risk, and suggestive inverse associations with FlOP_320 and FlOP_360 were observed. Several SNPs were associated with carotenoid levels, and a small number were suggestively associated with breast cancer risk. We observed evidence of interactions between some SNPs and carotenoid levels on risk. We did not observe consistent associations between circulating levels of premenopausal carotenoids or FlOP levels and breast cancer risk.

SUBMITTER: Sisti JS

PROVIDER: S-EPMC4437794 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses' health studies.

Sisti Julia S JS Lindström Sara S Kraft Peter P Tamimi Rulla M RM Rosner Bernard A BA Wu Tianying T Willett Walter C WC Eliassen A Heather AH

Breast cancer research and treatment 20150428 2

High levels of circulating carotenoids are hypothesized to reduce breast cancer risk, potentially due to their antioxidant properties. However, little is known about the relationship between carotenoid exposure earlier in life and risk. We examined associations of premenopausal plasma carotenoids and markers of oxidative stress and risk of breast cancer among 1179 case-control pairs in the Nurses' Health Study (NHS) and NHSII. Levels of α- and β-carotene, β-cryptoxanthin, lycopene, and lutein/ze ...[more]

PMID: 25917867

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Project description:Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.

Project description:IntroductionPrior research supports an association between endogenous sex steroids and breast cancer among postmenopausal women; the association is less clear among premenopausal women.MethodsWe evaluated the associations between estrogens, androgens, progesterone and sex hormone binding globulin (SHBG) and breast cancer in a nested case-control study in the Nurses' Health Study II. Between 1996 and 1999, 29,611 participants provided blood samples; 18,521 provided samples timed in early follicular and mid-luteal phases of the menstrual cycle. A total of 634 women, premenopausal at blood collection, developed breast cancer between 1999 and 2009 and were matched to 1,264 controls (514 cases and 1,030 controls with timed samples). We used conditional logistic regression controlling for breast cancer risk factors for overall analyses; unconditional logistic regression additionally controlling for matching factors was used for subgroup analyses.ResultsIn analyses of premenopausal estrogens including breast cancers diagnosed both before and after menopause, there was no association between follicular estradiol, estrone and free estradiol and risk of either total or invasive breast cancer. Luteal estradiol was positively associated with estrogen receptor positive (ER+)/progesterone receptor positive (PR+) cancers (5th vs. 1st quintile odds ratio (OR): 1.7 (95% confidence interval (CI): 1.0 to 2.9), Ptrend = 0.02). Luteal estrone, free estradiol and progesterone were not associated with risk. Androgens were suggestively or significantly associated with risk when the sample was restricted to invasive tumors (for example, testosterone: OR: 1.4 (1.0 to 2.0), Ptrend = 0.23) and ER+/PR+ disease (testosterone: OR: 1.7 (1.1 to 2.6) Ptrend = 0.10; dehydroepiandrosterone sulfate (DHEAS) OR: 1.3 (0.8 to 2.0) Ptrend = 0.05). SHBG was not associated with breast cancer risk. The results varied by menopausal status at diagnosis, with follicular estradiol suggestively positively associated with breast cancers in women premenopausal at diagnosis (OR: 1.1 (0.9 to 1.3) and significantly inversely associated with postmenopausal disease (OR: 0.6 (0.4 to 0.9); Pheterogeneity < 0.01).ConclusionsAndrogens were associated with modestly increased risk of breast cancer in this population, with stronger associations for invasive and ER+/PR+ disease. Luteal phase estradiol levels were suggestively associated with ER+/PR+ tumors but no other strong associations were observed with estrogens. Associations with follicular phase estrogens may vary by menopausal status at diagnosis, but case numbers were limited. Additional studies to confirm the role of premenopausal hormones in the etiology of both premenopausal and postmenopausal breast cancer are needed.

Project description:ImportanceThe association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation.ObjectiveTo investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics.Design, setting, and participantsThis multicenter analysis used pooled individual-level data from 758?592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13?082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017.ExposuresBody mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years.Main outcomes and measuresInvasive or in situ premenopausal breast cancer.ResultsAmong the 758?592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference,?0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI?35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall.Conclusions and relevanceThe results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

Dataset Information

Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses' health studies.

Publications

Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses' health studies.

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