Genetic and lifestyle influence on telomere length and subsequent risk of colon cancer in a case control study.
BACKGROUND
Telomeres cap the ends of chromosomes and help maintain genomic stability and integrity. Telomere length (TL) has been linked to a number of diseases, including a variety of cancers; however, the association between TL and risk for colorectal cancer is unclear.


METHODS
We investigate the association between genetic, diet, and lifestyle factors and TL and the association between TL and colorectal cancer using data from a population-based case-control study of colon (249 cases and 371 controls) and rectal cancer (276 cases and 372 controls) conducted in Utah. DNA samples came from immortalized cell lines for colon cancer and directly from whole blood for rectal cancer. We genotyped 11 single nucleotide polymorphisms in five genes associated with telomeres, TERT, MEN1, MRE11A, RECQL5, and TNKS.


RESULTS
TL was measured using quantitative PCR. TERT rs2853676 (p=0.044) and RECQL5 rs820152 (p=0.001) were associated with TL at <0.05 level of significance. After adjusting for age and sex, BMI and cigarette smoking were significantly inversely associated with TL among controls. Use of aspirin/NSAIDs interacted significantly with TERT rs10069690 and rs2242652 to alter TL. Longer TL was significantly associated with reduced colon cancer risk after adjusting for age and sex (OR = 0.94 95% confidence intervals 0.89-0.99 per decile of TL). Further adjustment for BMI and cigarette smoking attenuated the association so that it was no longer significant.


CONCLUSIONS
In summary several genetic and lifestyle factors were observed to influence TL. These factors also appear to confound associations between TL and colon cancer.
Department of Internal Medicine, University of Utah Health Sciences Center Salt Lake City, Utah, USA.
Andrew J
AJ
Pellatt
Roger K
RK
Wolff
Abbie
A
Lundgreen
Richard
R
Cawthon
Martha L
ML
Slattery