Genetic polymorphisms of genes whose products are responsible for activities, such as xenobiotic metabolism, mutagen detoxification and DNA-repair, have been predicted to be associated with the risk of developing lung cancer (LC). The association of LC with tobacco smoking has been extensively investigated, but no studies have focused on the Arab ethnicity. Previously, we examined the association between genetic polymorphisms among Phase I and Phase II metabolism genes and the risk of LC. Here, we extend the data by examining the correlation of OGG1 Ser326Cys combined with CYP1A1 (Ile462Val and MspI) and GSTP1 (Ile105Val and Ala103Val) polymorphisms with the risk of LC. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) and gene sequencing were carried out for genotyping the OGG1 polymorphisms of 123 LC patients and 129 controls. No significant differences in the frequencies of the OGG1 mutant allele between patients and controls were found. The distributions of heterozygous Ser/Cys or Cys/Cys genotypes of OGG1 were not associated with the risk of LC either according to the histological types of LC or based on waterpipe tobacco (WP) smoking status. In contrast, the combined effect of OGG1 variants with CYP1A1 and GSTP1 variants revealed a significant correlation with the OGG1 Ser326Cys-CYP1A1 MspI variants pairing. This association was significant (p = 0.001) in individuals who carried homozygous or heterozygous variant type genotypes of both genes in a reference with carriers of both wild-type genotypes (wt/wt − wt/wt). The odds ratios were 2.99 (95% CI 1.67-5.36), 2.68 (95% CI 1.08-6.62), and 2.80 (95% CI 1.18-6.69) for those who carried (wt/wt − wt/vt + vt/vt), (wt/vt + vt/vt − wt/wt), and (wt/vt + vt/vt − wt/vt + vt/ vt), respectively. The study suggests a limited correlation is present between carrying OGG1 Ser326Cys polymorphism and the risk of developing LC in Arab populations.

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The Forkhead box (FOX) protein family includes FOXA1, and is a transcription factor (TF). It work as a pioneer factor, interacting with compressed chromatin to allow ER to bind more easily later (Nagaraj and Ma, 2021). It significantly contributed to the development and invasiveness of endocrine-resistant cells by changing the ER dependent transcriptome in numerous endocrine-resistant preclinical BC cell types (Chun et al., 2017). The present study is done during the period September 2021 and May 2022 at the University of Kufa's, Faculty of Medicine, Middle Euphrates Unit for Cancer Research.  as a control group. These samples gathered from archives of the two private laboratories and re-evaluted by two pathologist. Positive nuclear IHC expression of FOXA1 is significantly reduced in 43 BC cases (58.9%) compared to 38 control persons (100%) while negative nuclear IHC expression of FOXA1 is significantly reduced in BC patients, 30 cases (41.1%) compared to 0 control  persons (0.0%), Odd ratio 1.66, 95% CI (1.37-1.98), P=0.0001. Moreover, FOXA1 positivity was elevated significantly in patients with grade I and II (P=0.002) and absent of lymph node metastasis (p=0.027).

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