To the best of our knowledge, the present nested, matched case-control study is the first to examine the relationship of mean leukocyte telomere length with risk of incident CRC in women. We found no evidence for an association, and the present null findings in white women support our recent findings in white men using a similar study design (12
Recent studies have shown telomere length shortening as an independent marker for the progression and/or prognosis of CRC (4
). However, these studies used colonocyte-telomere length measurements from paired cancerous-noncancerous tissue specimens from the same individuals, as opposed to PBL. Furthermore, it has been shown that telomere dynamics in colonocytes differ from other tissues including PBL (10
), due partly to the local dynamics of telomere-telomerase complex in cell proliferation (8
), and exposure/responses to oxidative damage (29
) in persons already had CRC. Moreover, a case-control study by Risques et al
) examining telomere length from various tissue types (including circulating leukocytes) in ulcerative colitis (UC), a chronic inflammatory condition that predisposes to CRC, a modest shortening in leukocytes from UC subjects (N=102) compared to the controls (N=45) was observed (p
=0.046). The authors hypothesized that the moderate shortening of leukocyte telomeres due to its proliferative properties and frequent travel through the inflamed colon. Taking altogether, the potential involvement of leukocyte telomere biology in CRC risk requires further investigation in future large prospective studies.
The nature of the present investigation in which the determination of a case status was based solely on the subsequent development of disease rather than on any arbitrary selection criteria designed by the investigators, greatly reduce the possibility of bias and confounding. Nonetheless, our study population consists of white females only, so the data may not be applicable to other ethnic groups, non-white men, or populations with different socioeconomic background. The present null findings could be partly due to bias from different environmental/lifestyle factors obtained for the present female sample population compared to those in our previous male sample population (12
), or play of chance. Furthermore, in contrast to our previous observation in men (12
), no correlation of leukocyte telomere length with age was observed. This may partly due to the present (age) matching selection criteria and the modest sample size of our control participants, from whom would be unlikely to capture enough variability of age to detect a relationship.
In our study, we had the ability to detect, based on the present sample size, assuming 80% power, at an alpha of 0.05, a difference in the loge-transformed TSR of <−0.218 or >0.218 between cases and controls. Thus, the present study may have limited power to detect a true, small-to-moderate difference of telomere length between cases and controls.
In conclusion, the present prospective, nested case-control study of white US women found no evidence for an association of mean leukocyte telomere length with risk of incident colorectal carcinoma. In concordance with our previous findings in a prospective, nested case-control study of middle-aged US white men, the present findings further suggest that leukocyte telomere length may not be a useful predictor for CRC risk assessment.