World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 14, Number 4, August 2023, pages 277-284

Association Between Telomere Length and Risk of Lung Cancer in an Asian Population: A Mendelian Randomization Study

Figure 1. Description of the study design in this two-sample MR study. (a) MR analyses depend on three core assumptions. (b) Sketch of the study design. LTL: leucocyte telomere length; MR: Mendelian randomization; SNPs: single nucleotide polymorphisms.

Figure 2. The casual effect of LTL on lung cancer. (a) Scatter plot of the association between LTL and risk of lung cancer. The four methods applied in the current manuscript were all depicted. Lines in black, red, green and blue represent for IVW, MR-Egger, weighted median and weighted mode models. (b) Forest plot was used to show the MR estimates and 95% CI values (gray line segment) for each SNP. As well, it also showed the IVW and MR-Egger MR results in the bottom. (c) Leave-one-out analysis was applied to evaluate whether any single instrumental variable was driving the causal effect. (d) Funnel plot was applied to detect whether the observed association was along with obviously heterogeneity. β: beta estimate; CI: confidence interval; IVW: inverse-variance weighted; LTL: leucocyte telomere length; OR: odds ratio; SE: standard error of the beta; SNPs: single nucleotide polymorphisms.

**Table 1.** Genetic Variants (n = 10) Applied to Estimate the Effect of LTL on Lung Cancer in MR Analyses
rsID	Chr	Pos	Effect allele	Other alleles	P for exposure	β	SE	P for outcome
β: beta estimate; Chr: chromosome number; LTL: leucocyte telomere length; MR: Mendelian randomization; Pos: chromosomal position; rsID: reference SNP ID; SE: standard error of the beta.
rs41293836	14	24721327	T	C	1.00 × 10^-200	0.233	0.017	7.78 × 10^-2
rs7705526	5	1285974	A	C	2.61 × 10^-38	0.118	0.010	2.83 × 10^-13
rs2293607	3	169482335	C	T	1.00 × 10^-200	-0.120	0.010	8.49 × 10^-3
rs12415148	10	105680586	C	T	2.78 × 10^-25	0.204	0.020	4.92 × 10^-2
rs3219104	1	226562621	C	A	2.43 × 10^-16	0.074	0.009	1.49 × 10^-2
rs28365964	8	73920883	C	T	6.96 × 10^-15	0.270	0.035	NA
rs10857352	4	164101482	G	A	1.60 × 10^-8	0.058	0.010	3.95 × 10^-1
rs41309367	20	62309554	T	C	1.16 × 10^-8	-0.058	0.010	2.69 × 10^-3
rs227080	11	108247888	G	A	1.87 × 10^-10	-0.060	0.009	7.10 × 10^-1
rs7776744	7	124599749	G	A	2.51 × 10^-10	-0.058	0.009	2.58 × 10^-1

Table 1. Genetic Variants (n = 10) Applied to Estimate the Effect of LTL on Lung Cancer in MR Analyses

rsID

Chr

Pos

Effect allele

Other alleles

P for exposure

P for outcome

β: beta estimate; Chr: chromosome number; LTL: leucocyte telomere length; MR: Mendelian randomization; Pos: chromosomal position; rsID: reference SNP ID; SE: standard error of the beta.

rs41293836

24721327

1.00 × 10^-200

0.233

0.017

7.78 × 10^-2

rs7705526

1285974

2.61 × 10^-38

0.118

0.010

2.83 × 10^-13

rs2293607

169482335

1.00 × 10^-200

-0.120

0.010

8.49 × 10^-3

rs12415148

105680586

2.78 × 10^-25

0.204

0.020

4.92 × 10^-2

rs3219104

226562621

2.43 × 10^-16

0.074

0.009

1.49 × 10^-2

rs28365964

73920883

6.96 × 10^-15

0.270

0.035

rs10857352

164101482

1.60 × 10^-8

0.058

0.010

3.95 × 10^-1

rs41309367

62309554

1.16 × 10^-8

-0.058

0.010

2.69 × 10^-3

rs227080

108247888

1.87 × 10^-10

-0.060

0.009

7.10 × 10^-1

rs7776744

124599749

2.51 × 10^-10

-0.058

0.009

2.58 × 10^-1

**Table 2.** Genetic Predicted the Association Between LTL and Lung Cancer in the MR Analyses
Exposure	Outcome	No. of SNPs	Methods	OR (95% CI)	β (SE)	P
β: beta estimate; CI: confidence interval; IVW: inverse-variance weighted; LTL: leucocyte telomere length; MR: Mendelian randomization; OR: odds ratio; SE: standard error of the beta; SNPs: single nucleotide polymorphisms.
LTL	Lung cancer	8	IVW	1.60 (1.31 - 1.97)	0.473 (0.104)	5.96 × 10^-6
			MR-Egger	1.44 (0.92 - 2.26)	0.367 (0.228)	1.60 × 10^-1
			Weighted median	1.56 (1.21 - 2.01)	0.444 (0.129)	5.99 × 10^-4
			Weighted mode	1.55 (1.19 - 2.04)	0.441 (0.139)	1.54 × 10^-2

Table 2. Genetic Predicted the Association Between LTL and Lung Cancer in the MR Analyses

Exposure

Outcome

No. of SNPs

Methods

OR (95% CI)

β (SE)

β: beta estimate; CI: confidence interval; IVW: inverse-variance weighted; LTL: leucocyte telomere length; MR: Mendelian randomization; OR: odds ratio; SE: standard error of the beta; SNPs: single nucleotide polymorphisms.

LTL

Lung cancer

IVW

1.60 (1.31 - 1.97)

0.473 (0.104)

5.96 × 10^-6

MR-Egger

1.44 (0.92 - 2.26)

0.367 (0.228)

1.60 × 10^-1

Weighted median

1.56 (1.21 - 2.01)

0.444 (0.129)

5.99 × 10^-4

Weighted mode

1.55 (1.19 - 2.04)

0.441 (0.139)

1.54 × 10^-2

**Table 3.** Pleiotropy and Heterogeneity Analyses
Exposure	Outcome	MR-Egger regression	MR-PRESSO	Heterogeneity analyses
IVW: inverse-variance weighted; LTL: leucocyte telomere length; MR: Mendelian randomization.
LTL	Lung cancer	0.012	0.615	0.448	NA	IVW	7.886	0.343
						MR-Egger	7.532	0.274

Table 3. Pleiotropy and Heterogeneity Analyses

Exposure

Outcome

MR-Egger regression

MR-PRESSO

Heterogeneity analyses

Intercept

P_intercept

Global test P

Correct P*

Method

P_Q

IVW: inverse-variance weighted; LTL: leucocyte telomere length; MR: Mendelian randomization.

LTL

Lung cancer

0.012

0.615

0.448

IVW

7.886

0.343

MR-Egger

7.532

0.274

**Table 4.** Genetic Predicted the Association Between LTL and Lung Cancer in the Multivariable MR Analyses
Exposure	Outcome	No. of SNPs	Methods	OR (95% CI)	P
LTL	Lung cancer	8	IVW	1.93 (1.37 - 2.73)	0.0002
			MR-Egger	1.81 (0.80 - 4.07)	0.1945
			Weighted median	1.57 (1.22 - 2.04)	0.0006
			Weighted mode	1.55 (1.20 - 2.00)	0.0093

Table 4. Genetic Predicted the Association Between LTL and Lung Cancer in the Multivariable MR Analyses

Exposure

Outcome

No. of SNPs

Methods

OR (95% CI)

LTL

Lung cancer

IVW

1.93 (1.37 - 2.73)

0.0002

MR-Egger

1.81 (0.80 - 4.07)

0.1945

Weighted median

1.57 (1.22 - 2.04)

0.0006

Weighted mode

1.55 (1.20 - 2.00)

0.0093