Common genetic variation of the IGF2 gene and epithelial ovarian cancer risk in Chinese population

Epithelial ovarian cancer (EOC) is a gynecological malignancy associated with high mortality, largely due to frequent diagnosis at advanced stages resulting from its asymptomatic early presentation. Although several single nucleotide polymorphisms (SNPs) have been implicated in EOC risk, its genetic determinants remain incompletely characterized. This study aimed to investigate the association between IGF2 polymorphisms (rs1004446, rs10840447, rs11602347, and rs4244808) and both susceptibility and clinicopathological characteristics of EOC in a Chinese population.

Genomic DNA was extracted from peripheral whole blood samples. The four candidate SNPs in IGF2 were genotyped in 213 EOC patients (211 serous) and 203 healthy controls using the MassARRAY platform.

The genotype frequencies of rs11602347 C > G (P < 0.0001) and rs4244808 T > G (P = 0.010) differed significantly between cases and controls. Genetic model analyses revealed that the rs11602347 C > G variant was associated with a reduced risk of EOC under dominant and additive models (CG + GG vs. CC: adjusted OR = 0.09, Benjamini-Hochberg adjusted P = 0.002; GG vs. CC: adjusted OR = 0.11, Benjamini-Hochberg adjusted P = 0.008), while the rs4244808 T > G variant was correlated with an increased risk under the recessive model (GG vs. TG + TT: adjusted OR = 2.51, Benjamini-Hochberg adjusted P = 0.016). Stratified analysis indicated that the protective effect of rs10840447 GG genotype was more pronounced in younger individuals (age ≤ 47: adjusted OR = 0.47, P = 0.028), whereas the TG + TT genotypes of rs4244808 were associated with significantly elevated EOC risk in older individuals (age > 47 :adjusted OR = 3.52, P = 0.015). Furthermore, among EOC cases, the GG genotype of rs11602347 was associated with an increased odds of advanced FIGO stage (III+IV vs. I+II: adjusted OR = 2.67, P = 0.034), while the GG genotype of rs4244808 was linked to a reduced odds of advanced FIGO stage (III + IV vs. I+ II: adjusted OR = 0.30, P = 0.032). Haplotype analysis showed that the GGGG* haplotype (rs1004446/rs10840447/rs11602347/rs4244808) was associated with an increased risk of EOC (OR = 2.16, P = 0.036).

These findings provide preliminary evidence that IGF2 gene polymorphisms may be associated with the risk and clinicopathological characteristics of serous EOC in Chinese women.