Telomere length in prospective and retrospective cancer case-control studies

Abstract

Previous studies have reported that shorter mean telomere length in lymphocytes was associated with increased susceptibility to common diseases of aging, and may be predictive of cancer risk. However, most analyses have examined retrospectively collected case-control studies. Mean telomere length was measured using high-throughput quantitative real-time PCR. Blood for DNA extraction was collected after cancer diagnosis in the East Anglian SEARCH Breast (2,243 cases and 2,181 controls) and SEARCH Colorectal (2,249 cases and 2,161 controls) studies. Prospective case-control studies were conducted for breast cancer (199 cases) and colorectal cancer (185 cases), nested within the EPIC-Norfolk cohort. Blood was collected at least 6 months prior to diagnosis, and was matched to DNA from two cancer-free controls per case. In the retrospective SEARCH studies, the age-adjusted odds ratios for shortest (Q4) versus longest (Q1) quartile of mean telomere length was 15.5 [95% confidence intervals (CI), 11.6-20.8; p-het = 5.7 x 10(-75)], with a "per quartile" P-trend = 2.1 x 10(-80) for breast cancer; and 2.14 (95% CI, 1.77-2.59; p-het = 7.3 x 10(-15)), with a per quartile P-trend = 1.8 x 10(-13) for colorectal cancer. In the prospective EPIC study, the comparable odds ratios (Q4 versus Q1) were 1.58 (95% CI, 0.75-3.31; p-het = 0.23) for breast cancer and 1.13 (95% CI, 0.54-2.36; p-het = 0.75) for colorectal cancer risk. Mean telomere length was shorter in retrospectively collected cases than in controls but the equivalent association was markedly weaker in the prospective studies. This suggests that telomere shortening largely occurs after diagnosis, and therefore, might not be of value in cancer prediction.