EURURO Vol. 72 No. 5

respectively)

[25,28]

, the reduced GRS effect estimate was

attenuated but remained statistically significant

(OR = 1.73 per predicted kilobase increase, 95% CI = 1.36

–

2.21,

0.0001; Supplementary Fig. 2).

A similar direct relationship between telomere length-

associated genetic variants and RCC risk was observedwhen

applying summary statistic based approaches to our RCC

cases and controls. The likelihood-based pooled estimate

for a predicted kilobase increase in telomere length is a

2.00 increase in the odds of developing RCC (95% CI = 1.64

–

2.43,

0.0001;

Fig. 3

). Likewise, the inverse variance

weighted method gave a similar effect estimate (OR = 1.96,

95% CI = 1.63

–

2.35,

0.0001). There was no significant

heterogeneity when comparing the ratio of effect sizes of

the genetic variants on telomere length to the effect sizes of

[(Fig._1)TD$FIG]

Fig. 1

–

Forest plot for associations of the telomere length associated genetic risk score with renal cell carcinoma risk. Odds ratios are scaled to

predicted kilobase increase in telomere length. Combined association

0.0001. Heterogeneity

= 0.96.

FE = fixed effects; IARC = International Agency for Cancer Research; MDA = MD Anderson Cancer Center; NCI = National Cancer Institute.

[(Fig._3)TD$FIG]

Fig. 3

–

The effect of each variant on telomere length and renal cell

carcinoma (RCC) risk. Estimates for the single nucleotide polymorphism

(SNP)

–

telomere and SNP

–

RCC associations are presented in

Table 1

. Error bars around each estimate are 95% confidence intervals

around the

estimate. A best fit regression line (dashed line) and 95%

confidence interval (shaded region) are plotted using the likelihood

based estimate (odds ratio = 2.00, 95% confidence interval = 1.64

–

2.43,

0.0001).

[(Fig._2)TD$FIG]

Fig. 2

–

Associations of telomere length genetic risk score (GRS) decile

with renal cell carcinoma. Dashed line represents the baseline for the

reference decile (lowest decile). Error bars represent 95% confidence

intervals around the odds ratio association for each GRS decile and

renal cell carcinoma.

E U R O P E A N U R O L O GY 7 2 ( 2 0 17 ) 74 7

–

7 5 4

751