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This finding suggests that having partial Ashkenazi Jewish ancestry may contribute to an increased risk of having high adjusted PMD. So you want people to cheat in their minds? Table Jewish large breasts describes the number of samples excluded from the analysis and the reasons they were excluded. Group 1 represented We spoke with Kaye about her process, her next steps and a few of her favorite things. Mammographic breast density and family history of breast cancer. I had been terrified to travel to Israel, but not for reasons of safety. And the proof is in the pudding: Statistics show that rhinoplasties are on the decline sincewhile breast reduction surgery has become increasingly more popular. My great uncle who kept kosher his whole life would fill his plate with it — and no one had the will to tell Jewish large breasts it probably did not meet the criteria.
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Here we report a finding of an association between genetic ancestry and adjusted PMD. We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age-adjusted and body mass index-adjusted PMD. Our final dataset included women with the highest adjusted PMD and with the lowest genotyped on the Illumina 1 M platform.
Principal component analysis PCA and identity-by-descent analyses allowed us to infer the women's genetic ancestry and correlate it with adjusted PMD. Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association. Women of Ashkenazi Jewish ancestry, based on genetic analysis, are more likely to have high age-adjusted and body mass index-adjusted PMD.
Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density. Percent mammographic density PMD is the proportion of radiographically dense breast tissue as a fraction of the entire breast and can be calculated from a two-dimensional mammogram image [ 1 - 3 ] or as a fraction of the entire volume of the breast [ 4 - 13 ].
PMD is a strong risk factor for breast cancer; women of the same age and body mass index BMI in the upper quartile of PMD have a fourfold to sixfold higher risk of breast cancer than women in the lower quartile [ 1 , 3 , 14 - 20 ]. Many of the risk factors for high PMD are also risk factors for breast cancer, including late parity and use of postmenopausal hormone therapy with estrogen and progestin [ 3 , 21 ].
However, reproductive and hormonal factors account for a small proportion of the variation in PMD [ 21 ], and PMD remains a risk factor for breast cancer when adjusting for these factors [ 22 , 23 ]. Both linkage and genome-wide association studies have been used to search for genetic determinants of PMD [ 29 - 33 ]. To date, the majority of heritability remains unexplained; for example, a recent genome-wide association study found SNP variants accounting for only 0.
Identifying an ethnic population with higher PMD may have implications for breast cancer risk in that population and could open new avenues to map genes for this trait. Study subjects were selected from 4, women enrolled in the California Pacific Medical Center Breast Health Cohort who underwent screening mammography between January and April and consented to provide blood specimens between July and June The questionnaire includes information on age, race, height, weight, parity history, postmenopausal hormone therapy use, personal history of breast cancer, and family history of breast cancer in mother, sister, or daughter.
We excluded women who reported a personal history of breast cancer. All participants gave informed consent to participate in the research. PMD was calculated from craniocaudal digitized film mammograms using single X-ray absorptiometry SXA , as described in [ 4 ]. In brief, the method makes two separate calculations: the total volumetric density and the total breast density.
PMD is calculated as the quotient of total volumetric density and total breast volume. To calculate the total volumetric density, a calibrated phantom reference material is placed in the unused corner of the film mammogram. The phantom is composed of two materials, one the same density as fat and the other the same density as fibroglandular tissue.
For each pixel of the mammogram, the percent density is calculated based on where that pixel falls on the gray scale from the low-density material to the high-density material. Total volumetric density is then calculated as the average of these values across all breast pixels. This method has been shown to be highly reproducible [ 4 ], and to be at least as strongly associated with breast cancer risk as traditionally estimated PMD [ 5 ].
We used the average PMD of the right and left breasts. For women who only had a value for PMD on one side, we used the measurement from the side with data. We used the residuals of this model as the adjusted PMD value for each woman. We selected women with adjusted PMD in the highest quintile and women with adjusted PMD in the lowest quintile for genotyping.
Of these, we were able to identify corresponding biospecimens from women in the top quintile and biospecimens from women in the bottom quintile. All 1, women were linked to the California Cancer Registry by the San Francisco Mammography Registry annually since to confirm the women did not develop breast cancer after their screening examination.
We used t tests and Wilcoxon rank-sum tests for continuous variables and used chi-square tests for categorical variables to determine whether there were significant differences between women with high adjusted PMD and women with low adjusted PMD for baseline characteristics and principal components PCs. For the combined PCA analysis, we used a subset of , SNPs that were genotyped on both the Illumina 1 M platform and the other Illumina platforms used in the reference datasets. Changing the European and Middle Eastern groups did not substantially change the first principal component PC1 data not shown.
Principal component analysis of participants from our study and additional reference samples of known ancestry. The first principal component PC1 separates people of Ashkenazi Jewish ancestry from other European groups.
The vertical dotted lines separate the Ashkenazi Jewish and Northern European clusters from the middle group. The diagonal dotted line divides the probably mixed Ashkenazi-other European group higher values on the second principal component PC2 from the Southern European group lower values on PC2. We performed multivariate logistic regression analysis on the outcome of high versus low adjusted PMD to assess whether the association between position on PC1 and adjusted PMD remained significant after adjusting for baseline characteristics using Stata software version For this analysis, we performed a linear transformation on PC1 in order to quantify the percent Ashkenazi Jewish ancestry on a scale of approximately 0 to After this transformation, a PC1 value of Unadjusted PMD and volume of mammographic density were significantly higher and total breast volume was lower in women with high adjusted PMD.
Postmenopausal women were more likely to have lower adjusted PMD. Women with high adjusted PMD were more likely to have reported a family history of breast cancer.
Characteristics of women with high adjusted percent mammographic density versus low adjusted percent mammographic density. PMD, percent mammographic density. Chi-squared P values calculated excluding the samples with unknown values. We performed PCA to determine the population substructure of our sample. Of the women included in the initial analysis, four women appeared to have a possible admixture with Asian or African ancestry Figure S2 in Additional File 1.
To simplify the analysis, we excluded these women from additional analyses. PC1 separated people of Ashkenazi Jewish ancestry from other European groups. Ashkenazi Jews have a significantly higher proportion of their genome that is IBD than other Caucasian populations [ 39 , 40 ].
We therefore performed analysis of IBD in our sample. Group 1 represented We compared the degree of IBD among pairs of women within each of the groups. The pairs of individuals in Group 4 averaged Using transformed values of PC1, with 0 representing the least amount of Ashkenazi Jewish ancestry as measured by PCA and 1 representing the greatest, having a PC1 value of 1 corresponded to an odds ratio OR of 2. P value of association between the first principal component and percent mammographic density PMD obtained using the Wilcoxon rank-sum test.
Multivariate regression of baseline characteristics and the first principal component with adjusted percent mammographic density. Odds ratios are for likelihood of having high adjusted percent mammographic density compared with low adjusted percent mammographic density. Univariate and multivariate P values are calculated using chi-squared tests. We performed additional analyses on individuals whose genetics suggested partial Ashkenazi Jewish ancestry to determine whether partial Ashkenazi Jewish ancestry was also associated with increased adjusted PMD.
The second PC with the ancestral populations included divided this middle group into individuals who clustered with known Southern European groups Group 2 and individuals who did not Group 3. We compared the probability of having high adjusted PMD between the group with mixed Ashkenazi Jewish ancestry Group 3 and the group with Southern European ancestry Group 2.
This finding suggests that having partial Ashkenazi Jewish ancestry may contribute to an increased risk of having high adjusted PMD. We performed an analysis of genetic ancestry and age-adjusted and BMI-adjusted PMD, a strong risk factor for breast cancer. We found that the highest value of Ashkenazi Jewish ancestry, as identified by PCA, was associated with a twofold greater risk of having an adjusted PMD in the top quintile.
When we analyzed women by clusters of ancestry, women who clustered with Ashkenazi Jews had a 1. This association was independent of total breast volume, parity, menopausal status, and postmenopausal hormone therapy.
The identification of an ethnic group with higher adjusted PMD has significant implications for strategies to identify the genetic basis of this trait. Ashkenazi Jews have probably undergone a population bottleneck followed by rapid expansion, consistent with being a founder population [ 41 , 42 ].
Founder populations are more likely to have unique variants that are otherwise absent or exceptionally rare in other populations [ 43 - 46 ]. Our finding suggests that women of Ashkenazi Jewish ancestry may have unique genetic variant s or higher frequencies of variants that predispose to higher adjusted PMD.
Although a genetic effect is a plausible explanation for the higher adjusted PMD in Ashkenazi Jewish women, we cannot rule out unmeasured nongenetic confounders. We adjusted for some factors known to be associated with PMD including age at parity, menopausal status, and use of postmenopausal hormone therapy. However, we did not adjust for other factors such as age at menarche or number of children. The finding that women of partial Ashkenazi Jewish ancestry also have higher adjusted PMD supports a genetic basis for the increased adjusted PMD in Ashkenazi Jews, although it is also possible that women of mixed Ashkenazi Jewish descent are exposed to the same environmental factors as women of Ashkenazi Jewish descent.
One limitation of our study is that we did not have information about whether these women self-identified as Ashkenazi Jews.
However, other genetic studies with self-identification information have identified Ashkenazi Jews as a cluster among US Caucasians [ 47 , 48 ].
Furthermore, individuals who self-identify as having partial Ashkenazi Jewish ancestry can also been identified by PCA [ 49 ]. Another limitation of our study was that our analysis depended on both the measurement of PMD using the SXA approach and on a sampling scheme that sampled the top and bottom quintiles. The SXA measurement of PMD is known to have high reproducibility [ 6 ] and has been associated with breast cancer risk [ 5 ].
In addition, we found an association between high adjusted PMD and family history of breast cancer, as has previously been observed with qualitative measures of breast density [ 50 , 51 ]. However, it is possible that the association between adjusted PMD and genetic ancestry is only apparent when measuring PMD using SXA and is an artifact of that method; additional studies of PMD and ancestry will be necessary to confirm that the association remains when different methods are used to measure PMD.
We therefore stratified by BMI quartile and by decile and re-adjusted for BMI in the multivariate analysis using these categories, and did not detect any attenuation of the main association between ancestry and adjusted PMD.
Future studies of PMD may benefit from adjusting for BMI initially by categories rather than using a linear regression to avoid having to adjust twice. The Ashkenazi Jewish population has been reported to have higher rates of breast cancer compared with other Caucasian populations [ 53 ], which may be at least partially explained by its high prevalence of two founder mutations in BRCA1 and one founder mutation in BRCA2 [ 54 ].
Ashkenazi Jews may have higher PMD because of genetic or environmental factors that increase PMD but have no impact on breast cancer risk. Alternatively, higher PMD in Ashkenazi Jews may result from previously unknown genetic risk factors for breast cancer development. Environmental risk factors, genetic variation, or both may explain this finding.
Ashkenazi Jews are a founder population with substantially higher IBD compared with other populations. One or more genetic variant s unique to this population may therefore increase PMD. Further research is needed to uncover potential genetic determinants underlying the higher adjusted PMD in this group, which in turn may shed new light on the biologic mechanisms of PMD. JLC performed the statistical analysis and data interpretation and drafted the manuscript. KK obtained funding, contributed to data acquisition and interpretation of the results, and made critical reviews to the manuscript.
SRC obtained funding, contributed to data acquisition and made critical reviews to the manuscript. DH and SH made contributions to the bioinformatics analysis and made critical reviews to the manuscript. EZ designed the study, obtained funding, provided interpretation of the data and helped to draft the manuscript.
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Chances are, the larger your breasts, the more choice words you have about sports bras. Kaye — a runner, dancer, and yoga teacher — wears a size 31G, so she knows a thing or two about sports bras for bustier women.
The company, says Kaye, is a tribute to her bubbe who died of breast cancer. The range of Bloom Bras are designed to fit women with cup sizes DD to K and band sizes from 31 to 44, and can be purchased online. We spoke with Kaye about her process, her next steps and a few of her favorite things. Most of us wear the wrong size bras for a lot of our lives.
Was this true for you? If so, when did you finally start wearing the right size? This is one of the subjects I am most passionate about. If you are a DDD, that is a full cup size. And we all hold differently. I get measured all of the time since I still step in as our fit model. Wearing the right bra is a life changer. The first thing I used to do when I would walk in the door is rip off my bra…and not because I was excited to see someone.
Taking that first leap. My background is in product development so I know the time, effort, and money it takes to launch a product along with the small chance of success. We launched on Kickstarter and it was the most insane thing. We hit our goal in less than 82 hours and doubled it.
You cited your grandmother as your inspiration. Can you tell us about one of your favorite memories with her? My grandmother [took] me on a plane when I was 6 months old. She instilled in me the love for adventure. For my bat mitzvah , she and my grandfather took me on a cruise through Europe exposing me to arts, culture, and theater.
I have so many funny memories as she was quite the character. The Marvelous Mrs. Maisel — I watched it in a weekend and am chomping at the bit for the next season. I am a caring intelligent, passionate adventurer with a quest for knowledge and a love for family. If someone says they will do something and does not — and people who are late.
If you are rude to wait staff, I have zero tolerance. Yellow jello. This is a lemon jello and whipped cream concoction that is served at dinner instead of dessert. My great uncle who kept kosher his whole life would fill his plate with it — and no one had the will to tell him it probably did not meet the criteria.
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