Association between prediagnostic leukocyte telomere length and breast cancer risk: the Singapore Chinese Health Study

Abstract

Background Telomeres and telomerase play key roles in the chromosomal maintenance and stability. Recent epidemiological studies have shown that longer telomeres are associated with increased risk of several cancer types. However, epidemiological data for telomere length and risk of breast cancer are sparse. Methods We prospectively studied the association between telomere length and risk of breast cancer in 14,305 middle-aged or older Chinese women of the Singapore Chinese Health Study including 442 incident breast cancer cases after 12.3 years of follow-up. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiple quantitative polymerase chain reaction method. The Cox proportional hazard regression method was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for breast cancer associated with longer telomeres after adjustment for potential confounders. Results Longer telomeres were significantly associated with higher risk of breast cancer in a dose-dependent manner ( P trend = 0.006); the highest quartile of telomere length was associated with a statistically significant 47% higher risk of breast cancer compared with the lowest quartile of telomere length after the adjustment for age and other known risk factors for breast cancer (HR Q4 vs Q1 = 1.47, 95% CI = 1.11, 1.94). Conclusions The findings of the present study support the hypothesis that longer telomeres may be a risk factor for breast cancer. Telomere length in peripheral blood leukocytes may be developed as a biomarker for breast cancer risk prediction. Electronic supplementary material The online version of this article (10.1186/s13058-019-1133-0) contains supplementary material, which is available to authorized users.

Leukocyte telomere length, cancer incidence and all‐cause mortality among Chinese adults: Singapore Chinese Health Study

“…Also, there was considerable heterogeneity in the characteristics of these study populations such as different geographical locations, male/female ratio, age at the measurement of telomere length, as well as difference in study design, sample size, DNA extraction method and telomere length measurement method among the studies included in that meta‐analysis ( I 2 = 70.4%, P for heterogeneity test < .001). In our previous analyses in the same cohort, we found a positive association for longer telomere length with increased risk of multiple specific cancer types including lung adenocarcinoma, 34 breast, 36 colorectal 37 and pancreatic 38 cancers. To date, there are only three nested case‐control studies conducted within the Shanghai Women's Health Study and one nested case‐control study based on the Taiwan Cancer Screening Program Cohort in Asian participants in which the associations of telomere length in peripheral blood leucocytes with the incidence of total lung cancer (a positive association), 46 breast cancer (an inverse association), 47 colorectal cancer (a U‐shaped association) 48 and hepatocellular carcinoma (no association) 49 have been evaluated and produced mixed results.…”

“…The results from these studies remain inconclusive; some found an inverse association [17][18][19][20][21][22][23][24][25][26] whereas others reported null findings [27][28][29][30][31][32][33] Data on other ethnic populations are sparse. We have previously reported that longer telomere length is associated with increased risk of developing several cancer types including lung adenocarcinoma, 34 gastric cancer, 35 breast cancer, 36 colorectal cancer 37 and pancreatic cancer. 38 Data on the role of telomere length on the risk of total mortality and total cancer risk have been lacking, especially in Asian populations who have distinct genetic risk factors and environmental and lifestyle factors profile patterns than their white counterparts.…”

Analysis of the autoimmune regulator (AIRE) gene variant rs2075876 (G/A) association with breast cancer susceptibility

“…analysis also revealed that AIRE is involved in "transcriptional misregulation in cancer" pathway (hsa05202) ( Table S2). Interestingly, all the above-mentioned pathways and processes were identified to play essential roles in BC etiology, progression, and/or outcome, [31][32][33][34][35][36][37][38][39] which add evidence to AIRE implication in the BC.…”

Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco

“…Shortened telomeres have been associated with many diseases, including certain cancers (30)(31)(32)(33)(34)(35)(36). However, telomere lengthening has also been associated with cancer (37)(38)(39), and there is evidence of an association between telomere lengthening and breast cancer (40)(41)(42)(43). Though the exact link between TL and cancer remains unclear, research suggests mechanisms by which lengthening or shortening may contribute to carcinogenesis.…”