Abstract A051: Prior chlamydial infection and ovarian cancer risk by tumor p53 expression
Authors: Sarina Pollat, Nicolas Wentzensen, Tim Waterboer, Manila Hada, Jolanta Lissowska, Beata Peplonska, Mark E. Sherman, Kara A. Michels, Britton Trabert
Journal: Cancer Research (2024)

Abstract Background: Prior infection with Chlamydia trachomatis, indicated by the presence of circulating antibodies against plasmid encoded glycoprotein 3 (Pgp3), is associated with an increased risk of ovarian cancer. The aberrant expression of p53 can be found in up to 95% of ovarian cancers and is an especially frequent feature among high-grade serous cancers. Prior studies have described mechanisms by which Chlamydia reprogram DNA damage response pathways, including those involving p53. However, tumor level expression of p53 among women with and without prior exposure to chlamydia is poorly described. We evaluated whether the association between prior chlamydial infection (Pgp3 seropositivity) and ovarian cancer varied by tumor p53 expression and whether Pgp3 seropositivity was associated with ovarian tumor expression of p53. Methods: Available serologic data for Pgp3 in tubo-ovarian cancer cases (n=155) and matched controls (n=556) from the Polish Ovarian Cancer Study were evaluated and stratified by p53 mutation status of cases inferred from immunohistochemical staining. Expression of p53 was assessed in tissue microarrays (2+ cores per case) and classified as aberrant (i.e., no expression or overexpression: ≥60% positive cells) or wild- type. Multinomial logistic regression with controls as the reference was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of Pgp3 seropositivity with ovarian cancer with stratification by p53 expression among the cases. Logistic regression among cases was only used to evaluate the association between Pgp3 and aberrant p53 expression. Results: Aberrant p53 expression was found in 70% of cases. Pgp3 seropositivity was associated with increased ovarian cancer risk (OR [95% CI]: 1.86 [1.28-2.68]). Pgp3 seropositivity was associated with risk for both p53 aberrant (1.79 [1.16-2.75]) or p53 wild-type ovarian cancers (2.06 [1.11-3.80], p for heterogeneity=0.80). When restricted to high-grade serous cancers, the association with Pgp3 was also not differential by p53 status (p for heterogeneity=0.16; 83% of high-grade serous cases had aberrant p53 expression). Among women with cancer, Pgp3 seropositivity was not associated with aberrant p53 expression (versus wild-type, OR [95% CI]: 0.90 [0.45-1.81], spearman correlation: -0.05, p-value=0.55). Conclusion/Discussion: Our study provides support that previous C. trachomatis infection is associated with ovarian cancer, irrespective of aberrant p53 tumor expression. There are many possible mechanisms by which Chlamydia may influence ovarian cancer. While the current results do not rule out interactions with p53-related pathways, it is likely that C. trachomatis increases ovarian cancer risk via multiple mechanisms (e.g., infection related sequelae like chronic inflammation). Citation Format: Sarina Pollat, Nicolas Wentzensen, Tim Waterboer, Manila Hada, Jolanta Lissowska, Beata Peplonska, Mark E. Sherman, Kara A. Michels, Britton Trabert. Prior chlamydial infection and ovarian cancer risk by tumor p53 expression [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A051.