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Chromosome 9 arm-specific telomere length and breast cancer risk.

ABSTRACT: Telomere dysfunction is involved in the development of breast cancer and very short telomeres are frequent genetic alterations in breast tumors. However, the influence of telomere lengths of specific chromosomal arms on the breast cancer risk is unknown.We conducted a case-control study of breast cancer to examine the associations of the telomere length on chromosome 9 short arms (9p) and long arms (9q) with risk of breast cancer. Chromosome 9 arm-specific telomere lengths were measured by quantitative fluorescent in situ hybridization using cultured blood lymphocytes.Telomere length on chromosome 9p was significantly shorter in breast cancer patients than in control subjects (P < 0.001). Using the 50th percentile value in controls as a cut point, women who have short 9p telomeres had an increased risk of breast cancer [adjusted odds ratio (OR) = 2.6; 95% confidence interval (CI) = 1.5-4.3]. When the 9p telomere length was divided into quartiles, a significant inverse dose-response relationship between 9p telomere length and breast cancer risk was observed (P(trend) < 0.001), with a quartile ORs of 3.0 (95% CI = 1.2-7.5), 3.9 (95% CI = 1.6-9.5) and 6.6 (95% CI = 2.8-15.9) for third, second and first quartile, respectively, when compared with women in the fourth quartile.Short telomere length on chromosome 9p is strongly associated with the risk of breast cancer. If confirmed by future studies, chromosome 9p telomere length has the potential to be incorporated into the current prediction models to significantly enhance breast cancer risk prediction.

SUBMITTER: Zheng YL

PROVIDER: S-EPMC2718080 | biostudies-other | 2009 Aug

REPOSITORIES: biostudies-other

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Chromosome 9 arm-specific telomere length and breast cancer risk.

Zheng Yun-Ling YL Loffredo Christopher A CA Shields Peter G PG Selim Sahar M SM

Carcinogenesis 20090617 8

<h4>Background</h4>Telomere dysfunction is involved in the development of breast cancer and very short telomeres are frequent genetic alterations in breast tumors. However, the influence of telomere lengths of specific chromosomal arms on the breast cancer risk is unknown.<h4>Methods</h4>We conducted a case-control study of breast cancer to examine the associations of the telomere length on chromosome 9 short arms (9p) and long arms (9q) with risk of breast cancer. Chromosome 9 arm-specific telo ...[more]

PMID: 19535548

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Project description:BackgroundTelomeres at the ends of eukaryotic chromosomes play a critical role in maintaining the integrity and stability of the genome and participate in the initiation of DNA damage/repair responses.MethodsWe performed a case-control study to evaluate the role of three SNPs (TERT-07, TERT-54 and POT1-03) in telomere maintenance genes previously found to be significantly associated with breast cancer risk. We used sister-sets obtained from the New York site of the Breast Cancer Family Registry (BCFR). Among the 313 sister-sets, there were 333 breast cancer cases and 409 unaffected sisters who were evaluated in the current study. We separately applied conditional logistic regression and generalized estimating equations (GEE) models to evaluate associations between the three SNPs and breast cancer risk within sister-sets. We examined the associations between genotype, covariates and telomere length among unaffected sisters using a GEE model.ResultsWe found no significant associations between the three SNPs in telomere maintenance genes and breast cancer risk by both conditional logistic regression and GEE models, nor were these SNPs significantly related to telomere length. Among unaffected sisters, shortened telomeres were statistically significantly correlated with never hormone replacement therapy (HRT) use. Increased duration of HRT use was significantly associated with reduced telomere length. The means of telomere length were 0.77 (SD = 0.35) for never HRT use, 0.67 (SD = 0.29) for HRT use < 5 yrs and 0.59 (SD = 0.24) for HRT use ≥ 5 yrs after adjusting for age of blood donation and race and ethnicity.ConclusionsWe found that exogenous hormonal exposure was inversely associated with telomere length. No significant associations between genetic variants and telomere length or breast cancer risk were observed. These findings provide initial evidence to understand hormonal exposure in the regulation of telomere length and breast cancer risk but need replication in prospective studies.

Dataset Information

Chromosome 9 arm-specific telomere length and breast cancer risk.

Publications

Chromosome 9 arm-specific telomere length and breast cancer risk.

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