High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium

Lauren C. Peres; Adrianne R. Mallen; Mary K. Townsend; Elizabeth M. Poole; Britton Trabert; Naomi E. Allen; Alan A. Arslan; Laure Dossus; Renee T. Fortner; Inger T. Gram; Patricia Hartge; Annika Idahl; Rudolf Kaaks; Marina Kvaskoff; Anthony M. Magliocco; Melissa A. Merritt; J. Ramon Quiros; Anne Tjønneland; Antonia Trichopoulou; Rosario Tumino; Carla H. van Gils; Kala Visvanathan; Nicolas Wentzensen; Anne Zeleniuch-Jacquotte; Shelley S. Tworoger

doi:10.1158/0008-5472.can-19-1554

High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium

Lauren C. Peres, Adrianne R. Mallen, Mary K. Townsend, Elizabeth M. Poole, Britton Trabert, Naomi E. Allen, Alan A. Arslan, Laure Dossus, Renee T. Fortner, Inger T. Gram, Patricia Hartge, Annika Idahl, Rudolf Kaaks, Marina Kvaskoff, Anthony M. Magliocco, Melissa A. Merritt, J. Ramon Quiros, Anne Tjønneland, Antonia Trichopoulou, Rosario TuminoCarla H. van Gils, Kala Visvanathan, Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Shelley S. Tworoger

Section of Environmental Health

10 Citations (Scopus)

Abstract

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; P_{heterogeneity} ¼ 0.20). Heterogeneity was observed with oral contraceptive use (P_interaction 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.

Original language	English
Journal	Cancer Research
Volume	79
Issue number	20
Pages (from-to)	5442-5451
Number of pages	10
ISSN	0008-5472
DOIs	https://doi.org/10.1158/0008-5472.can-19-1554
Publication status	Published - 15 Oct 2019

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Peres, L. C., Mallen, A. R., Townsend, M. K., Poole, E. M., Trabert, B., Allen, N. E., Arslan, A. A., Dossus, L., Fortner, R. T., Gram, I. T., Hartge, P., Idahl, A., Kaaks, R., Kvaskoff, M., Magliocco, A. M., Merritt, M. A., Quiros, J. R., Tjønneland, A., Trichopoulou, A., ... Tworoger, S. S. (2019). High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium. Cancer Research, 79(20), 5442-5451. https://doi.org/10.1158/0008-5472.can-19-1554

Peres, LC, Mallen, AR, Townsend, MK, Poole, EM, Trabert, B, Allen, NE, Arslan, AA, Dossus, L, Fortner, RT, Gram, IT, Hartge, P, Idahl, A, Kaaks, R, Kvaskoff, M, Magliocco, AM, Merritt, MA, Quiros, JR, Tjønneland, A, Trichopoulou, A, Tumino, R, van Gils, CH, Visvanathan, K, Wentzensen, N, Zeleniuch-Jacquotte, A & Tworoger, SS 2019, 'High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium', Cancer Research, vol. 79, no. 20, pp. 5442-5451. https://doi.org/10.1158/0008-5472.can-19-1554

@article{60657a79ee924e5e93584fb8cc8ac5e6,

title = "High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium",

abstract = "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.",

author = "Peres, {Lauren C.} and Mallen, {Adrianne R.} and Townsend, {Mary K.} and Poole, {Elizabeth M.} and Britton Trabert and Allen, {Naomi E.} and Arslan, {Alan A.} and Laure Dossus and Fortner, {Renee T.} and Gram, {Inger T.} and Patricia Hartge and Annika Idahl and Rudolf Kaaks and Marina Kvaskoff and Magliocco, {Anthony M.} and Merritt, {Melissa A.} and Quiros, {J. Ramon} and Anne Tj{\o}nneland and Antonia Trichopoulou and Rosario Tumino and {van Gils}, {Carla H.} and Kala Visvanathan and Nicolas Wentzensen and Anne Zeleniuch-Jacquotte and Tworoger, {Shelley S.}",

year = "2019",

month = oct,

day = "15",

doi = "10.1158/0008-5472.can-19-1554",

language = "English",

volume = "79",

pages = "5442--5451",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research",

number = "20",

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TY - JOUR

T1 - High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: 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, J. Ramon

AU - Tjønneland, 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.

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.

U2 - 10.1158/0008-5472.can-19-1554

DO - 10.1158/0008-5472.can-19-1554

M3 - Journal article

C2 - 31462430

SN - 0008-5472

VL - 79

SP - 5442

EP - 5451

JO - Cancer Research

JF - Cancer Research

IS - 20

ER -

High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium

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