TY - JOUR
T1 - High levels of C-reactive protein are associated with an increased risk of ovarian cancer
T2 - Results from the ovarian cancer Cohort Consortium
AU - Peres, Lauren C.
AU - Mallen, Adrianne R.
AU - Townsend, Mary K.
AU - Poole, Elizabeth M.
AU - Trabert, Britton
AU - Allen, Naomi E.
AU - Arslan, Alan A.
AU - Dossus, Laure
AU - Fortner, Renee T.
AU - Gram, Inger T.
AU - Hartge, Patricia
AU - Idahl, Annika
AU - Kaaks, Rudolf
AU - Kvaskoff, Marina
AU - Magliocco, Anthony M.
AU - Merritt, Melissa A.
AU - Quiros, Ramon J.
AU - Tjonneland, Anne
AU - Trichopoulou, Antonia
AU - Tumino, Rosario
AU - Van Gils, Carla H.
AU - Visvanathan, Kala
AU - Wentzensen, Nicolas
AU - Zeleniuch-Jacquotte, Anne
AU - Tworoger, Shelley S.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research. mechanism of ovarian carcinogenesis in a seminal paper by Ness and Cottreau (2), which has been supported by growing epidemiologic evidence. Conditions of chronic inflammation, such as endometriosis and pelvic inflammatory disease, are risk factors for ovarian cancer (3, 4), while anti-inflammatory exposures, such as aspirin use, are associated with a decreased risk (5-7). "Incessant ovulation" (8), which links physiologic damage of the ovarian surface epithelium during ovulation to an increase in inflammatory mediators (e.g., cytokines, prostaglandins) that can enhance tumorigenesis, is further implicated in ovarian cancer development. A greater number of ovulations increases a woman's risk for ovarian cancer (9) and the converse holds true for factors that interrupt ovulation (e.g., pregnancy, oral contraceptive use; refs. 10-12).
PY - 2019/10/15
Y1 - 2019/10/15
N2 - Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR ¼ 1.67; 95% CI ¼ 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR ¼ 9.67; 95% CI ¼ 1.10-84.80) and endometrioid carcinoma (OR ¼ 3.41; 95% CI ¼ 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR ¼ 1.43; 95% CI ¼ 0.82-2.49) and clear cell carcinoma (OR ¼ 2.05; 95% CI ¼ 0.36-11.57; Pheterogeneity ¼ 0.20). Heterogeneity was observed with oral contraceptive use (Pinteraction ¼ 0.03), where the increased risk was present only among ever users (OR ¼ 3.24; 95% CI ¼ 1.62-6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma. Significance: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.
AB - Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR ¼ 1.67; 95% CI ¼ 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR ¼ 9.67; 95% CI ¼ 1.10-84.80) and endometrioid carcinoma (OR ¼ 3.41; 95% CI ¼ 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR ¼ 1.43; 95% CI ¼ 0.82-2.49) and clear cell carcinoma (OR ¼ 2.05; 95% CI ¼ 0.36-11.57; Pheterogeneity ¼ 0.20). Heterogeneity was observed with oral contraceptive use (Pinteraction ¼ 0.03), where the increased risk was present only among ever users (OR ¼ 3.24; 95% CI ¼ 1.62-6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma. Significance: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.
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U2 - 10.1158/0008-5472.CAN-19-1554
DO - 10.1158/0008-5472.CAN-19-1554
M3 - Article
C2 - 31462430
AN - SCOPUS:85073305633
SN - 0008-5472
VL - 79
SP - 5442
EP - 5451
JO - Cancer Research
JF - Cancer Research
IS - 20
ER -