Genetic Variations in the Fibronectin 1 Gene (FN1) and Risk of Female Reproductive Cancers-A Preliminary Study

We investigated five single-nucleotide variants (SNVs) of the FN1 gene in female reproductive organ cancers. The proteins expressed by this gene are essential components of the extracellular matrix (ECM) that constitutes the tumor microenvironment (TME). The study group included 208 women diagnosed with cervical, uterine, and ovarian cancers and 208 age-matched cancer-free controls. Genomic DNA from whole blood was used to analyze five intronic SNVs of the FN1 gene using PCR/RFLP. The results indicate that two of the studied FN1 gene variants may increase the risk of gynecological cancers in dominant and log-additive models (p = 0.048 and p = 0.040 for rs6725958, p = 0.033 and p = 0.038 for rs1968510, respectively). Comparing individual cancer groups with the controls, differences were observed for the ovarian cancer group (rs1968510 p = 0.015 and p = 0.016, rs6725958 p = 0.070 and p = 0.037 in dominant and log-additive models, respectively). None of these associations remained statistically significant after Bonferroni correction for multiple testing. Haplotype analyses revealed that the AGATC haplotype, containing minor alleles for rs35343655 and rs6725958, was more frequent in the entire gynecological cancer group (p = 0.0036). For individual cancer types, values of p = 0.0071 for ovarian, p = 0.0028 for endometrial, and p = 0.0269 for cervical cancers were obtained; Our preliminary study suggests that the rs6725958 and rs1968510 FN1 variants may slightly increase the risk of female reproductive system cancers, particularly ovarian cancer. These findings require further validation in larger, independent cohorts and functional studies.