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Breast Cancer Research
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Breast Cancer Research
Article
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Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort

Authors: Woolcott, Christy G; Maskarinec, Gertraud; Haiman, Christopher A; Verheus, Martijn; Pagano, Ian S; Le Marchand, Loïc; Henderson, Brian E; +1 Authors

Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort

Abstract

Abstract Introduction Mammographic density is a strong risk factor for breast cancer. Our objective was to examine its association with polymorphisms identifying breast cancer susceptibility loci that were ascertained in recent genome-wide association studies. Methods Subjects were 825 women who participated in previous case–control studies of mammographic density and genetic factors nested within the Multiethnic Cohort study and were from three ethnic groups (White, Japanese American, Native Hawaiian). Eight polymorphisms (rs2981582 in FGFR2, rs3803662 and rs12443621in TOX3, rs3817198 in LSP1, rs981782 and rs10941679 near HCN1/MRPS30, rs889312 in MAP3K1, and rs13387042 at 2q) were examined. Mammographic density was quantified with a computer-assisted method as the percent dense area: the area of radiologically dense fibroglandular tissue relative to the total breast area that also includes radiologically lucent fatty tissue. Results The polymorphism rs12443621 in TOX3 was associated with percent dense area; women with at least one G allele (previously associated with increased breast cancer risk) had 3% to 4% higher densities than women with two A alleles. The polymorphism rs10941679 near HCN1/MRPS30 was also associated with percent dense area; women who were homozygous for the G allele (previously associated with increased breast cancer risk) had 4% to 5% lower densities than women with at least one A allele. The other polymorphisms were not associated with percent dense area. Conclusions The available data suggest that the effects of most of these polymorphisms on breast cancer are not mediated by mammographic density. Some effects may have been too small to be detected. The association with rs12443621 may provide clues as to how variation in TOX3 influences breast cancer risk.

Keywords

Medicine(all), Breast Neoplasms, Middle Aged, Prognosis, Polymorphism, Single Nucleotide, Neoplasm Proteins, Cohort Studies, Survival Rate, Risk Factors, Ethnicity, Humans, Female, Genetic Predisposition to Disease, Prospective Studies, Research Article, Aged, Mammography, Neoplasm Staging

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
25
Average
Top 10%
Top 10%
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gold