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

Abstract

Telomeres play a key role in chromosomal maintenance and stability. To date, few studies have investigated the association of leukocyte telomere length with risk of cancer incidence and all-cause mortality in a large prospective cohort, particularly of the Asian population. Relative telomere lengths in genomic DNA from peripheral blood samples were quantified using a validated quantitative real-time PCR among 26 540 middle-aged or older Chinese adults. Hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer and deaths by quintiles of telomere length were calculated using the Cox proportional hazards regression method with adjustment for age, sex and other potential confounders. After baseline blood collection, 4353 persons developed cancer and 7609 died. Participants with the longest decile of telomeres had a 26% (95% CI: 11%-44%) higher risk of total cancer incidence compared to the shortest decile after controlling for age, sex and other potential founders (P_trend < .0001). In contrast, longer telomeres were associated with lower risk of all-cause mortality (HR = 0.93; 95% CI: 0.84-1.03), noncancer death (HR = 0.81; 95% CI: 0.71-0.92), specifically, death from chronic obstructive pulmonary disease and pneumonia (HR = 0.79, 95% CI: 0.70-0.89) and digestive diseases (HR = 0.60, 95% CI: 0.42-0.88). Our findings demonstrated that longer telomeres are associated with increased risk of cancer development overall and several common cancer types including breast, rectal, prostate, pancreatic cancer and lung adenocarcinoma. Our study also confirmed that longer telomeres are associated with a reduced risk of noncancer related death.

Keywords: all‐cause mortality; biomarkers; cancer incidence; prospective cohort study; telomere length.

FIGURE 1

Associations between relative telomere length and risk of all-cause, cancer and noncancer mortality. Hazard ratios with 95% confidence intervals of mortality from all causes, cancer and noncancer causes by decile or one-SD increment of telomere length. Crude hazard ratios

FIGURE 2

Associations between relative telomere length and risk of all-cause, cancer and noncancer mortality. Hazard ratios with 95% confidence intervals of mortality from all causes, cancer and noncancer causes by decile or one-SD increment of telomere length. Hazard ratios were adjusted for age at blood collection, sex, dialect group, body mass index category, level of education, smoking status, number of cigarettes per day, number of years of smoking, daily alcohol consumption, weekly vigorous work or strenuous sports, number of hours of sleep per night and self-reported histories of physician-diagnosed diabetes mellitus, hypertension, stroke, ischemic heart disease and cancer. Longer telomeres were associated with a lower risk of mortality from all causes and noncancer related causes but associated with a higher risk of mortality from cancer

FIGURE 3

Associations between relative telomere length and risk of cause-specific mortality. Hazard ratios with 95% confidence intervals of mortality from selected causes other than cancer by one-SD increment of telomere length with adjustment for age at blood collection, sex, dialect group, body mass index category, level of education, smoking status, number of cigarettes per day, number of years of smoking, daily alcohol consumption, weekly vigorous work or strenuous sports, number of hours of sleep per night and self-reported histories of physician-diagnosed diabetes mellitus, hypertension, stroke, ischemic heart disease and cancer. Longer telomeres were associated with a lower risk of mortality from chronic obstructive pulmonary disease (COPD) and digestive diseases

FIGURE 4

Associations between relative telomere length and risk of total cancer incidence. Hazard ratios with 95% confidence intervals of total cancer incidence by decile or one-SD increment of telomere length with adjustment for age at blood collection, sex, dialect group, body mass index category, level of education, smoking status, number of cigarettes per day, number of years of smoking, daily alcohol consumption, weekly vigorous work or strenuous sports, number of hours of sleep per night and self-reported histories of physician-diagnosed diabetes mellitus, hypertension, stroke, ischemic heart disease and cancer. Longer telomeres were associated with a higher risk of total cancer incidence

FIGURE 5

Associations between relative telomere length and risk of cancer-specific incidences. Hazard ratios with 95% confidence intervals of selected specific cancer types with at least 100 cases per one-SD increment of telomere length with adjustment for age at blood collection, sex, dialect group, body mass index category, level of education, smoking status, number of cigarettes per day, number of years of smoking, daily alcohol consumption, weekly vigorous work or strenuous sports, number of hours of sleep per night and self-reported histories of physician-diagnosed diabetes mellitus, hypertension, stroke, ischemic heart disease and cancer. Longer telomeres were associated with a significantly higher risk of breast cancer, rectal cancer, pancreatic cancer and lung adenocarcinoma