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Educational differences in postmenopausal breast cancer--quantifying indirect effects through health behaviors, body mass index and reproductive patterns.

ABSTRACT: Studying mechanisms underlying social inequality in postmenopausal breast cancer is important in order to develop prevention strategies. Standard methods for investigating indirect effects, by comparing crude models to adjusted, are often biased. We applied a new method enabling the decomposition of the effect of educational level on breast cancer incidence into indirect effects through reproductive patterns (parity and age at first birth), body mass index and health behavior (alcohol consumption, physical inactivity, and hormone therapy use). The study was based on a pooled cohort of 6 studies from the Copenhagen area including 33,562 women (1,733 breast cancer cases) aged 50-70 years at baseline. The crude absolute rate of breast cancer was 399 cases per 100,000 person-years. A high educational level compared to low was associated with 74 (95% CI 22-125) extra breast cancer cases per 100,000 person-years at risk. Of these, 26% (95% CI 14%-69%) could be attributed to alcohol consumption. Similar effects were observed for age at first birth (32%; 95% CI 10%-257%), parity (19%; 95%CI 10%-45%), and hormone therapy use (10%; 95% CI 6%-18%). Educational level modified the effect of physical activity on breast cancer. In conclusion, this analysis suggests that a substantial number of the excess postmenopausal breast cancer events among women with a high educational level compared to a low can be attributed to differences in alcohol consumption, use of hormone therapy, and reproductive patterns. Women of high educational level may be more vulnerable to physical inactivity compared to women of low educational level.

SUBMITTER: Hvidtfeldt UA

PROVIDER: S-EPMC3812044 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Educational differences in postmenopausal breast cancer--quantifying indirect effects through health behaviors, body mass index and reproductive patterns.

Hvidtfeldt Ulla Arthur UA Lange Theis T Andersen Ingelise I Diderichsen Finn F Keiding Niels N Prescott Eva E Sørensen Thorkild I A TI Tjønneland Anne A Rod Naja Hulvej NH

PloS one 20131024 10

Studying mechanisms underlying social inequality in postmenopausal breast cancer is important in order to develop prevention strategies. Standard methods for investigating indirect effects, by comparing crude models to adjusted, are often biased. We applied a new method enabling the decomposition of the effect of educational level on breast cancer incidence into indirect effects through reproductive patterns (parity and age at first birth), body mass index and health behavior (alcohol consumptio ...[more]

PMID: 24205296

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Project description:Background:Elevated body mass index (BMI) is associated with increased risk of postmenopausal breast cancer. The underlying mechanisms, however, remain elusive. Methods:In a nested case-control study of 621 postmenopausal breast cancer case participants and 621 matched control participants, we measured 617 metabolites in prediagnostic serum. We calculated partial Pearson correlations between metabolites and BMI, and then evaluated BMI-associated metabolites (Bonferroni-corrected ? level for 617 statistical tests = P < 8.10?×?10-5) in relation to invasive breast cancer. Odds ratios (ORs) of breast cancer comparing the 90th vs 10th percentile (modeled on a continuous basis) were estimated using conditional logistic regression while controlling for breast cancer risk factors, including BMI. Metabolites with the lowest P values (false discovery rate < 0.2) were mutually adjusted for one another to determine those independently associated with breast cancer risk. Results:Of 67 BMI-associated metabolites, two were independently associated with invasive breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR?=?1.65, 95% confidence interval [CI] = 1.22 to 2.22) and 3-methylglutarylcarnitine (OR?=?1.67, 95% CI?=?1.21 to 2.30). Four metabolites were independently associated with estrogen receptor-positive (ER+) breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR?=?1.84, 95% CI?=?1.27 to 2.67), 3-methylglutarylcarnitine (OR?=?1.91, 95% CI?=?1.23 to 2.96), allo-isoleucine (OR?=?1.76, 95% CI?=?1.23 to 2.51), and 2-methylbutyrylcarnitine (OR?=?1.89, 95% CI?=?1.22 to 2.91). In a model without metabolites, each 5 kg/m2 increase in BMI was associated with a 14% higher risk of breast cancer (OR?=?1.14, 95% CI?=?1.01 to 1.28), but adding 16a-hydroxy-DHEA-3-sulfate and 3-methylglutarylcarnitine weakened this association (OR?=?1.06, 95% CI?=?0.93 to 1.20), with the logOR attenuating by 57.6% (95% CI?=?21.8% to 100.0+%). Conclusion:These four metabolites may signal metabolic pathways that contribute to breast carcinogenesis and that underlie the association of BMI with increased postmenopausal breast cancer risk. These findings warrant further replication efforts.

Project description:Background: The gut microbiota is increasingly recognized as playing an important role in the development of obesity, but the influence of gender remains elusive. Using a large cohort of Chinese adults, our study aimed to identify differences in gut microbiota as a function of body mass index (BMI) and investigate gender specific features within these differences. Methods: Five hundred fifty-one participants were categorized as underweight, normal, overweight, or obese, based on their BMI. Fecal microbiome composition was profiled via 16S rRNA gene sequencing. Generalized linear model (GLM), BugBase, PICRUSt, and SPIEC-EASI were employed to assess the variabilities in richness, diversity, structure, organism-level microbiome phenotypes, molecular functions, and ecological networks of the bacterial community that associated with BMI and sex. Results: The bacterial community of the underweight group exhibited significantly higher alpha diversity than other BMI groups. When stratified by gender, the pattern of alpha diversity across BMI was maintained in females, but no significant difference in alpha diversity was detected among the BMI groups of males. An enrichment of Fusobacteria was observed in the fecal microbiota of obese males, while obese females demonstrated an increased relative abundance of Actinobacteria. Analysis of microbial community-level phenotypes revealed that underweight males tend to have more anaerobic and less facultatively anaerobic bacteria, indicating a reduced resistance to oxidative stress. Functionally, butyrate-acetoacetate CoA-transferase was enriched in obese individuals, which might favor energy accumulation. PhoH-like ATPase was found to be increased in male obese subjects, indicating a propensity to harvest energy. The microbial ecological network of the obese group contained more antagonistic microbial interactions as well as high-degree nodes. Conclusion: Using a large Chinese cohort, we demonstrated BMI-associated differences in gut microbiota composition, functions, and ecological networks, which were influenced by gender. Results in this area have shown variability across several independent studies, suggesting that further investigation is needed to understand the role of the microbiota in modulating host energy harvest and storage, and the impact of sex on these functions.

Dataset Information

Educational differences in postmenopausal breast cancer--quantifying indirect effects through health behaviors, body mass index and reproductive patterns.

Publications

Educational differences in postmenopausal breast cancer--quantifying indirect effects through health behaviors, body mass index and reproductive patterns.

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