Dataset Information

Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium.

ABSTRACT:

Background

Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites.

Methods

We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests.

Results

Most associations did not vary by tumor site (P _het ≥ 0.05). Associations between first pregnancy (P _het = 0.04), tubal ligation (P _het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P _het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P _het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases.

Conclusions

Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site.

Impact

Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

SUBMITTER: Fortner RT

PROVIDER: S-EPMC7541500 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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 = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10-84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82-2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36-11.57; P heterogeneity = 0.20). Heterogeneity was observed with oral contraceptive use (P interaction = 0.03), where the increased risk was present only among ever users (OR = 3.24; 95% CI = 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.