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Int J Mol Epidemiol Genet 2012;3(3):184-194
Original Article
Genetic and lifestyle influence on telomere length and subsequent risk of
colon cancer in a case control study
Andrew J Pellatt, Roger K Wolff, Abbie Lundgreen, Richard Cawthon, Martha L Slattery
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Human
Genetics, University of Utah, Salt Lake City, Utah, USA
Received May 29, 2012; accepted August 15, 2012; Epub August 31, 2012; Published September 15, 2012
Abstract: 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. (IJMEG1205002).
Keywords: TERT, MEN1, RECQL5, MRE11A, TNKS, Colorectal cancer, telomere length
Address all correspondence to:
Dr. Martha L Slattery
Department of Internal Medicine
University of Utah Health Sciences Center
295 Chipeta Way
Salt Lake City, Utah 84108, USA.
Tel: 801-585-6955; Fax: 801-581-3623
E-mail: marty.slattery@hsc.utah.edu
Original Article
Genetic and lifestyle influence on telomere length and subsequent risk of
colon cancer in a case control study
Andrew J Pellatt, Roger K Wolff, Abbie Lundgreen, Richard Cawthon, Martha L Slattery
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Human
Genetics, University of Utah, Salt Lake City, Utah, USA
Received May 29, 2012; accepted August 15, 2012; Epub August 31, 2012; Published September 15, 2012
Abstract: 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. (IJMEG1205002).
Keywords: TERT, MEN1, RECQL5, MRE11A, TNKS, Colorectal cancer, telomere length
Address all correspondence to:
Dr. Martha L Slattery
Department of Internal Medicine
University of Utah Health Sciences Center
295 Chipeta Way
Salt Lake City, Utah 84108, USA.
Tel: 801-585-6955; Fax: 801-581-3623
E-mail: marty.slattery@hsc.utah.edu
