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Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged

ABSTRACT: The histone protein family member X (H2AFX) is important in maintaining chromatin structure and genetic stability. Genetic variants in H2AFX may alter protein functions and thus cancer risk. In this case-control study, we genotyped four common single nucleotide polymorphisms (i.e., -1654A > G [rs643788], -1420G > A [rs8551], and -1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3' untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-free controls. All female subjects were non-Hispanic whites aged T polymorphism. Therefore, we believe that H2AFX promoter polymorphisms may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Larger association studies and related functional studies are warranted to confirm these findings.

SUBMITTER: Lu J

PROVIDER: S-EPMC3030478 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged <or=55 years.

Lu Jiachun J Wei Qingyi Q Bondy Melissa L ML Brewster Abenaa M AM Bevers Therese B TB Yu Tse-Kuan TK Buchholz Thomas A TA Meric-Bernstam Funda F Hunt Kelly K KK Singletary S Eva SE Wang Li-E LE

Breast cancer research and treatment 20070913 2

The histone protein family member X (H2AFX) is important in maintaining chromatin structure and genetic stability. Genetic variants in H2AFX may alter protein functions and thus cancer risk. In this case-control study, we genotyped four common single nucleotide polymorphisms (i.e., -1654A > G [rs643788], -1420G > A [rs8551], and -1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3' untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-f ...[more]

PMID: 17851762

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Project description:Obesity increases the risk of heart failure and atrial fibrillation. Left atrial (LA) dysfunction is increasingly recognized as a mediator of cardiovascular disease. Early effects of obesity on LA function have not been examined in large population samples. We quantified LA strain and strain rate (SR) through speckle tracking echocardiography in 1,531 middle-aged community-based participants enrolled in the Asklepios study. We compared LA function between individuals with body mass index (BMI) < 25 kg/m2 (n?=?779), 25 to 29.9 kg/m2 (n?=?618) and ? 30 kg/m2 (n?=?134). Significant differences in reservoir longitudinal LA strain (BMI < 25 kg/m2?=?35.3%, BMI 25-29.9 kg/m2?=?33.1%, and BMI ? 30 kg/m2?=?30.9%; p < 0.00001) strain rate ([SR] BMI < 25 kg/m2?=?151; BMI 25 to 29.9 kg/m2?=?141; and BMI ? 30 kg/m2?=?135 %/s; p <0.00001) and expansion index (BMI < 25 kg/m2?=?1.6, BMI 25 to 29.9 kg/m2?=?1.4, and BMI ? 30 kg/m2?=?1.4; p <0.00001) were seen, indicating reduced reservoir function with increasing BMI. Obesity was also associated with impaired LA conduit function, including conduit longitudinal LA strain (BMI < 25 kg/m2?=?21.6%, BMI 25 to 29.9 kg/m2?=?18.9%, and BMI ? 30 kg/m2?=?16.7%; p <0.00001), SR (BMI < 25 kg/m2?=?-189, BMI 25 to 29.9 kg/m2?=?166, and BMI ? 30 kg/m2?=?150 %/s; p <0.0001) and passive LA emptying fraction (BMI < 25 kg/m2?=?40.5, BMI 25 to 29.9 kg/m2?=?36.5, and BMI ? 30 kg/m2?=?36%, p <0.00001). These differences persisted after adjustment for age, gender and other potential confounders. In contrast to reservoir and conduit function, obesity was associated with increased booster pump function (active LA emptying fraction: BMI < 25 kg/m2?=?19.4%, BMI 25 to 29.9 kg/m2?=?20.5%, and BMI ? 30 kg/m2?=?21.5%; p <0.00001). In middle-aged adults, obesity is associated with impaired reservoir and conduit LA function and higher booster function, which may be compensatory. Loss of booster LA function, either because of more advanced LA dysfunction or atrial fibrillation, may play an important role in precipitating heart failure in obese individuals.

Dataset Information

Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged

Publications

Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged <or=55 years.

Similar Datasets

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