No association between TERT-CLPTM1L single nucleotide polymorphism rs401681 and mean telomere length or cancer risk.
BACKGROUND
A recent study reported genetic variants in the TERT-CLPTM1L locus that were associated with mean telomere length, and with risk of multiple cancers.


METHODS
We evaluated the association between single nucleotide polymorphism (SNP) rs401681 (C > T) and mean telomere length, using quantitative real-time PCR, in blood-extracted DNA collected from 11,314 cancer-free participants from the Sisters in Breast Screening study, the Melanoma and Pigmented Lesions Evaluative Study melanoma family study, and the SEARCH Breast, Colorectal, Melanoma studies. We also examined the relationship between rs401618 genotype and susceptibility to breast cancer (6,800 cases and 6,608 controls), colorectal cancer (2,259 cases and 2,181 controls), and melanoma (787 cases and 999 controls).


RESULTS
The "per T allele" change in mean telomere length (DeltaCt), adjusted for age, study plate, gender, and family was 0.001 [95% confidence intervals (CI), 0.01-0.02; P trend = 0.61]. The "per T allele" odds ratio for each cancer was 1.01 for breast cancer (95% CI, 0.96-1.06; P trend = 0.64), 1.02 for colorectal cancer (95% CI, 0.94-1.11; P trend = 0.66), and 0.99 for melanoma (95% CI, 0.84-1.15; P trend = 0.87).


CONCLUSIONS
We found no evidence that this SNP was associated with mean telomere length, or with risk of breast cancer, colorectal cancer, or melanoma.


CONCLUSIONS
Our results indicate that the observed associations between rs401681 and several cancer types might be weaker than previously described. The lack of an association in our study between this SNP and mean telomere length suggests that any association with cancer risk at this locus is not mediated through TERT.
Pooley
Karen A
KA
Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, Strangeways Research Laboratory, 2 Worts Causeway, Cambridge CB18RN, United Kingdom. karen.pooley@srl.cam.ac.uk
Tyrer
Jonathan
J
Shah
Mitul
M
Driver
Kristy E
KE
Leyland
Jean
J
Brown
Judith
J
Audley
Tina
T
McGuffog
Lesley
L
Ponder
Bruce A J
BA
Pharoah
Paul D P
PD
Easton
Douglas F
DF
Dunning
Alison M
AM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D014408:Biomarkers, Tumor; C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase