Anticancer Res: Effect of interleukin-18 genotype on the risk of acute lymphoblastic leukemia in children in Taiwan

Acute lymphoblastic leukemia (ALL) is a disease
caused by the uncontrolled proliferation of lymphoid progenitor cells.
In general, ALL is the most prevalent pediatric hematological malignancy and primarily attacks children
aged 2 to 5 years.
There is evidence that interleukin-18 (IL-18) has antitumor and pro-tumor effects
on various types of leukemia.
Therefore, the current study by a research team aims to investigate the contribution of IL-18 polymorphisms to the risk of
acute lymphoblastic leukemia (ALL) in children in Taiwan.

The team used polymerase chain reaction-restriction fragment length polymorphism to determine the IL-18 promoter −656 (rs1946519), −607 (rs1946518), and -137 (rs187238) genotypes
in 266 children with ALL and 266 controls.

Figure: Interleukin-18 (IL-18) rs1946519, rs1946518, and rs187238 polymorphisms on chromosome 11

The results showed that there was no significant difference in genotype and allele frequency distribution between IL-18 rs1946519, rs1946518 or rs187238 in children with ALL cases and control groups (all p>0.
05).

However, in the stratified analysis of cases, IL-18 rs187238 GC and CC genotypes were associated with an increased risk of ALL and shortened survival in children (OR=4.
19 and 2.
93, 95% CI=2.
04–8.
64 and 1.
19–7.
23, p=0.
0001 and 0.
0250).

No association with rs1946519 and rs1946518 was found (both p>0.
05).

In this study, researchers evaluated the contribution of the IL-18 genotype to the risk of ALL in a representative population in Taiwan, consisting
of 266 children with ALL and the same number of healthy controls.
The data showed that the IL-18 rs1946519, rs1946518, and rs187238 genotypes were not associated
with the risk of ALL in children.
Therefore, these IL-18 SNPs may not be useful biomarkers
for early detection of ALL in children in Taiwan.
Notably, they found that the IL-18 rs187238 GC+ CC genotype was associated
with a higher risk of ALL and shorter survival in children.
This is a novel finding that is very useful
for prognostic prediction.
These findings also support the idea that IL-18 somehow plays a key role in the etiology of ALL, although the detailed mechanisms need to be further studied
.

There have been no reports
of the role of the IL-18 genotype in ALL.
The association of the genotypes of IL-18 rs1946518 and rs187238 with the risk of various types of solid cancers has been studied, such as esophageal, colorectal, ovarian, bladder, prostate, breast, and lung cancers
.
Overexpression of IL-18 in serum has been reported as a good marker for solid cancers such as lung cancer
.
However, it is unclear
whether serum IL-18 levels are a good marker of ALL.
There is evidence that high circulating levels of IL-18 are associated with a reduced risk of AML, but the dynamics of the IL-18 protein make it difficult to determine whether the IL-18 protein can be a good marker of ALL
.
Although more research is needed on detailed mechanisms, the current results also suggest that the GG genotype of IL-18 rs187238 can predict ALL survival in
children.

Overall, this preliminary study suggests that the IL-18 rs1946519, rs1946518, and rs187238 genotypes cannot be used as prognostic predictors of ALL risk in children, as shown in
other solid tumors.
However, the variant GC and CC genotypes of IL-18 rs187238 can be used as predictors
of high risk and shorter survival.

Original source:

Chen CC, Tzeng HE, Kuo CC, Lim SNS, Hsu PC, Hsu YN, Chin YT, Chang WS, Wang CH, Tsai CW, Pei JS, Bau DT.
Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese.
Anticancer Res.
2022 Nov; 42(11):5283-5290.
doi: 10.
21873/anticanres.
16035.
PMID: 36288881.