J Breast Cancer.  2018 Dec;21(4):391-398. 10.4048/jbc.2018.21.e52.

Shorter Telomere Length Is Associated with Increased Breast Cancer Risk in a Chinese Han Population: A Case-Control Analysis

• Wang Z
• Zhang Z
• Guo Y
• Shui H
• Liu G
• Jin T
• Wang H

• KMID: 2429817
• DOI: http://doi.org/10.4048/jbc.2018.21.e52

Abstract

PURPOSE
The aim of this study was to investigate the association of telomere length with breast cancer risk. We simultaneously explored the association between telomerase reverse transcriptase gene polymorphisms and telomere length.
METHODS
We used real-time quantitative polymerase chain reaction to measure relative telomere length (RTL) in genomic DNA extracted from peripheral blood from 183 breast cancer cases and 191 healthy controls. Genotyping was performed using the Sequenom MassARRAY platform.
RESULTS
Our results show that breast cancer patients had significantly shorter RTLs than control subjects (p < 0.05). When the RTLs were categorized into tertiles, we found that the lowest RTL was significantly associated with increased breast cancer risk compared with the highest RTL (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.40-3.90; p=0.001). Subgroup analyses indicated that risk of breast cancer was also significantly increased in the lowest RTL compared with the highest RTL in age >40 years (OR, 2.41; 95% CI, 1.31-4.43; p=0.005), body mass index ≤24 kg/m2 (OR, 2.81; 95% CI, 1.55-5.10; p=0.001), and postmenopausal women (OR, 3.94; 95% CI, 1.63-9.51; p=0.002), respectively. In addition, individuals with the AA genotype of rs2853677 have longer telomeres than those of breast cancer patients with the AG genotype (p=0.011).
CONCLUSION
Our results suggest that shorter RTL was associated with an increased risk of breast cancer. An association was found between the AA genotype of rs2853677 and longer RTLs in the case group. Functional studies are warranted to validate this association and further investigate our findings.

Keyword

Breast neoplasms; Polymorphism; Real-time polymerase chain reaction; Risk; Telomere

MeSH Terms

Asian Continental Ancestry Group*
Body Mass Index
Breast Neoplasms*
Breast*
Case-Control Studies*
DNA
Female
Genotype
Humans
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Telomerase
Telomere*
DNA
Telomerase

Figure

• 

  Figure 1 Mean relative telomere length (RTL) in breast cancer cases and healthy controls. (A) Reduced mean RTL of breast cancer cases (n=183) compared to controls (n=191). The distribution of mean RTL between case and control groups at the subgroup level for age (B), body mass index (BMI) (C), and menopause status (D). Horizontal lines represent the mean RTL; p-values were calculated using the Mann-Whitney U-test.

• 

  Figure 2 Restricted cubic spline curve assessing the association between relative telomere length (RTL) and breast cancer risk. Solid line represents the odds ratios; dotted lines represent the 95% confidence intervals.

• 

  Figure 3 Relative telomere length (RTL) in 191 controls and 183 breast cancer patients according to telomerase reverse transcriptase polymorphisms genotypes distribution. (A) rs2242652; (B) rs10069690; (C) rs2853677. Boxes represent the interquartile range of distributions (25th–75th percentile); horizontal lines within the boxes represent the medians; vertical lines represent the 5th and 95th percentiles; p-values were calculated using chi-square test (two-sided). p<0.05 indicates statistical significance.

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