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Life-course body size and perimenopausal mammographic parenchymal patterns in the MRC 1946 British birth cohort.

ABSTRACT: Dense mammographic parenchymal patterns are associated with an increased risk of breast cancer. Certain features of body size have been found to be associated with breast cancer risk, but less is known about their relation to breast density. We investigated the association of birth size, childhood growth and life-course changes in body size with Wolfe grade in 1298 perimenopausal women from a British cohort of women born in 1946. The cohort benefits from repeated measures of body size in childhood and adulthood. We obtained mammograms for 90% of women who at age 53 years reported having previously had a mammogram. We found no associations with birth weight or maximum attained height. Body mass index (BMI) at age 53 years and breast size were independently and inversely associated with Wolfe grade (P-value for trend <0.001 for both). Women who reached puberty later were at a greater odds of a higher Wolfe grade than women who had an earlier puberty (odds ratio associated with a 1 year delay in menarche 1.14, 95% CI: 1.01-1.27, adjusted for BMI and breast size at mammography). A higher BMI at any age during childhood or adult life was associated with a reduction in the odds of a higher Wolfe grade, after controlling for breast size and BMI at mammography, for example, standardised odds ratio for height at age 7 was 0.72 (95% CI: 0.64, 0.81). These findings reveal the importance of taking life-course changes in body size, and not just contemporaneous measures, into account when using mammographic density as an intermediate marker for risk of breast cancer.

SUBMITTER: McCormack VA

PROVIDER: S-EPMC2394467 | biostudies-other | 2003 Sep

REPOSITORIES: biostudies-other

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Project description:Mammographic density (MD) is a strong risk factor for breast cancer, but the biological mechanism underlying this association is not clear. Current adult body mass index (BMI) is inversely associated with percent MD; however, few studies have included Hispanic women or evaluated associations with measures of body fatness earlier in life. ESMaestras was established in 2006, when 28,345 women ages ?35 responded to a detailed questionnaire that assessed possible disease risk factors, including body fatness in childhood, adolescence, and young adulthood. In 2007, 2084 ESMaestras participants underwent a clinical examination, which included measurements of weight, height, and sitting height and a mammogram. We measured percent MD using a computer-assisted method. The current analysis includes 972 premenopausal and 559 postmenopausal women. We used multivariable linear regression to evaluate associations between measures of body size and MD, independent of current BMI. Among pre- and postmenopausal women, we observed no significant associations between body fatness during childhood, adolescence, or young adulthood and percent MD. Among postmenopausal women, we observed a modest positive association between body fatness immediately before first pregnancy and between ages 25 and 35 after adjustment for current BMI, with differences of 4.9 and 3.6 % points, respectively, in percent MD between the heaviest and leanest women (p-trend = 0.02). There were no significant associations between height, sitting height, and percent MD among pre- or postmenopausal women in multivariable models adjusting for BMI. In general, we found no clear associations between measures of body size in early life, current sitting height, or current height, and percent MD, after adjusting for current BMI, in this population of Mexican women. Our observation of a positive association between early adult body fatness (i.e., before first pregnancy and ages 25-35) and percent MD among postmenopausal women is inconsistent with prior research and requires confirmation in other studies.

Project description:Evidence for the contribution of individual foods and nutrients to bone health is weak. Few studies have considered hypothesis-based dietary patterns and bone health. We investigated whether a protein-calcium-potassium-rich (PrCaK-rich) dietary pattern over the adult life course, was positively associated with bone outcomes at 60 to 64 years of age. Diet diaries were collected at ages 36, 46, 53, and 60 to 64 years in 1263 participants (661 women) from the MRC National Survey of Health and Development. DXA and pQCT measurements were obtained at age 60 to 64 years, including size-adjusted bone mineral content (SA-BMC) and volumetric bone mineral density (vBMD). A food-based dietary pattern best explaining dietary calcium, potassium, and protein intakes (g/1000 kcal) was identified using reduced rank regression. Dietary pattern Z-scores were calculated for each individual, at each time point. Individual trajectories in dietary pattern Z-scores were modeled to summarize changes in Z-scores over the study period. Regression models examined associations between these trajectories and bone outcomes at age 60 to 64 years, adjusting for baseline dietary pattern Z-score and other confounders. A consistent PrCaK-rich dietary pattern was identified within the population, over time. Mean ± SD dietary pattern Z-scores at age 36 years and age 60 to 64 years were -0.32 ± 0.97 and 2.2 ± 1.5 (women) and -0.35 ± 0.98 and 1.7 ± 1.6 (men), respectively. Mean trajectory in dietary pattern Z-scores ± SD was 0.07 ± 0.02 units/year. Among women, a 0.02-SD unit/year higher trajectory in dietary pattern Z-score over time was associated with higher SA-BMC (spine 1.40% [95% CI, 0.30 to 2.51]; hip 1.35% [95% CI, 0.48 to 2.23]), and vBMD (radius 1.81% [95% CI, 0.13 to 3.50]) at age 60 to 64 years. No statistically significant associations were found in men. During adulthood, an increasing score for a dietary pattern rich in protein, calcium, and potassium was associated with greater SA-BMC at fracture-prone sites in women. This study emphasizes the importance of these nutrients, within the context of the whole diet, to bone health. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

Project description:BackgroundA neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age.MethodsParticipants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old. Using MRI data from a previously defined selection of this cohort, we derived brain-predicted age from an established machine-learning model (trained on 2001 healthy adults aged 18-90 years); subtracting this from chronological age (at time of assessment) gave the brain-predicted age difference (brain-PAD). We tested associations with data from early life, midlife, and late life, as well as rates of MRI-derived brain atrophy.FindingsBetween May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. We included 456 participants (225 female), with a mean chronological age of 70·7 years (SD 0·7; range 69·2 to 71·9). The mean brain-predicted age was 67·9 years (8·2, 46·3 to 94·3). Female sex was associated with a 5·4-year (95% CI 4·1 to 6·8) younger brain-PAD than male sex. An increase in brain-PAD was associated with increased cardiovascular risk at age 36 years (β=2·3 [95% CI 1·5 to 3·0]) and 69 years (β=2·6 [1·9 to 3·3]); increased cerebrovascular disease burden (1·9 [1·3 to 2·6]); lower cognitive performance (-1·3 [-2·4 to -0·2]); and increased serum neurofilament light concentration (1·2 [0·6 to 1·9]). Higher brain-PAD was associated with future hippocampal atrophy over the subsequent 2 years (0·003 mL/year [0·000 to 0·006] per 5-year increment in brain-PAD). Early-life factors did not relate to brain-PAD. Combining 12 metrics in a hierarchical partitioning model explained 33% of the variance in brain-PAD.InterpretationBrain-PAD was associated with cardiovascular risk, and imaging and biochemical markers of neurodegeneration. These findings support brain-PAD as an integrative summary metric of brain health, reflecting multiple contributions to pathological brain ageing, and which might have prognostic utility.FundingAlzheimer's Research UK, Medical Research Council Dementia Platforms UK, Selfridges Group Foundation, Wolfson Foundation, Wellcome Trust, Brain Research UK, Alzheimer's Association.

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Life-course body size and perimenopausal mammographic parenchymal patterns in the MRC 1946 British birth cohort.

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