EURURO Vol. 72 No. 5

Platinum Priority

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Editorial

Referring to the article published on pp. 747

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754 of this issue

Longer Telomere Length and Renal Cell Carcinoma

Jozefina Casuscelli

a , * , A. Ari Hakimi b

Department of Urology, Ludwig-Maximilians University, Munich, Germany;

Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer

Center, New York, NY, USA

Rapid advances in the genotyping methodology have

allowed us to affordably scan single nucleotide polymor-

phisms (SNPs) in the human genome

[1] .

SNPs are

alterations in the nucleotide sequence of the DNA, mostly

resulting in synonymous changes of the coding sequence,

and are the most common form of genomic variation. There

are approximately 10 million known SNPs in the human

genome, and the clinical relevance of these variants is often

studied within genome-wide association studies (GWASs).

Indeed, since the first successful publication of a GWAS in

the year 2005, the genome of hundreds and thousands of

humans has been tested to identify variations associated

with different complex traits or diseases.

GWASs have revolutionized the understanding of

disease susceptibility by correlating specific genetic

variations to the overall risk of disease. The identified

variants often, however, account for a relatively low risk of

developing a specific disease and therefore require a large

samples size analyzed in a case

–

control fashion. Further,

functional implications of a given SNP are often challeng-

ing to discern given that they are rarely related to the

known mechanisms of disease development, and also

because a substantial amount of SNPs is located in the

noncoding DNA regions, which are only beginning to be

explored.

Nevertheless, in cancer research, GWASs have been

proved to be an intriguing tool to understand disease

susceptibility. Most of the variations are specific for a given

tissue or cancer, but emerging evidence points to SNPs that

can contribute to more than one type of cancer

[2,3] .

For instance, genetic variants conferring longer telomere

length have shown in different GWASs the correlation with

an increased risk for site-specific cancers, such as chronic

lymphocytic leukemia, glioma, neuroblastoma, and lung

and bladder cancer

[4] .

Telomeres are located at the end of every chromosome,

and function to protect chromosomes from recombination

and degradation. They are gradually shortened following

every cell division, ultimately leading to senescence and

apoptosis of the cell after a given amount of divisions.

Upregulated telomerase enzyme can maintain the telomere

length, which eventually results in immortalization of cells.

This enzyme is active in the embryonal period, but also

during tumorigenesis, enabling malignant cells to divide

continuously

[5]

Several recent studies including those on renal cell

carcinoma (RCC) demonstrated longer telomere length and

increased telomerase activity in tumor tissues, and proven

association with advanced disease and reduced survival

[6]

In this month

’

s issue of

European Urology

, Machiela and

colleagues

[7]

present a meta-analysis of genetic variants

associated with telomere length in peripheral blood

leukocytes and test their utility as inherited biomarkers

for RCC risk. Previous GWAS interrogations of RCC and

telomeres have generated conflicting results, and were

likely to be underpowered and have used less sensitive

methods.

Here, the authors present the findings from six

independent GWASs, all of European Ancestry, analyzing

the genotypes of over 10 000 RCC cases and over

20 000 cancer-free controls. The studied variants were

used as a surrogate of telomere length and were aggregated

to create a genetic risk score to assess genetically inferred

telomere length. To obviate the effects of biases due to

confounders and reverse causation, an analysis of the

association between telomere length and RCC risk was

E U R O P E A N U R O L O GY 7 2 ( 2 0 17 ) 7 5 5 – 7 5 6

ava ilable at

www.sciencedirect.com

journal homepage:

www.eu ropeanurology.com

DOI of original article:

http://dx.doi.org/10.1016/j.eururo.2017.07.015

* Corresponding author. Department of Urology, Ludwig-Maximilians University, Marchioninistrasse 15, Munich 81377, Germany. Tel. +49 4400 0;

Fax: +49 4400 78890.

E-mail address:

jozefina.casuscelli@med.uni-muenchen.de

(J. Casuscelli).

http://dx.doi.org/10.1016/j.eururo.2017.08.008