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Principal Investigator
Rodger Rothenberger
University of Cincinnati
Position Title
About this CDAS Project
PLCO (Learn more about this study)
Project ID
Initial CDAS Request Approval
Oct 10, 2019
Tobacco smoking is associated with increased tumor grade and stage and grade along with the mucinous carcinoma histopathologic type.
Primary Hypothesis:
Tobacco smoking is associated with increased tumor grade and stage and grade along with the mucinous carcinoma histopathologic type.
PLCO database will be queried for data regarding patients’ smoking status (all data variables from section 22 of the PLCO Ovary Person Data Dictionary), Data regarding Cancer characteristics including stage, histologic grade, and histopathologic type (all data variables from section 14 of Ovary Person Data Dictionary), data regarding treatment with variables from section 2 of Ovary Treatment Data Dictionary, and, finally Data from Section 17 of the Ovary Person Data dictionary with specific attention to the Days Until Death (dth_days) variable. It is with this information that a determination of whether there is a dose dependent relationship between tobacco smoking and ovarian cancer grade and stage at presentation. Secondary hypothesis will utilize this data set to determine if smoking status/history is predictive of poor response to Bevacizumab – described within the variable 288="Other chemotherapy (specify)".

Epithelial ovarian cancer accounts for nearly 90% of all ovarian tumors – with four main histotypes: serous (70%), endometrioid (10%), clear cell (13%), and mucinous (3%). The influence of environmental factors in the development of ovarian cancer has been previously studied. It has been previously proposed that high-grade serous cancer may originate in the fallopian tube epithelium, endometrioid and clear cell cancers may originate from endometrial epithelium, mucinous carcinoma is and that mucinous carcinoma may arise at the tuboperitoneal junction1
The association of smoking and ovarian cancer has been studied through various epidemiologic studies and meta-analyses with recent studies showing new associations within the realm of ovarian cancer and smoking – which should be viewed within the lens of this delineation and proposed differing pathophysiology. Multiple studies have shown that current smoking is associated with increased risk of mucinous cancer. Zhou et al. in 2019 conducted a meta-analysis of 31 studies assessing ovarian cancer risk and survival and found that there was evidence of a decreased risk of clear cell and endometrioid cancers. No significant association between cigarette smoking and serous cancer was found. Zhou et al. Further found that an increased risk of ovarian cancer mortality associated with smoking2.
Further evidence of a dose-response relationship between smoking and ovarian cancer was published this year by Yarmolinsky et al. This study examined 25,509 women with epithelial ovarian cancer and 40,941 controls of European descent and looked at previously reported risk factors for ovarian cancer through a mendelian risk analysis. It found that lifetime smoking exposure was associated with invasive epithelial ovarian cancer with overall risk increasing with increased smoking exposure3.
To this point, a correlation of grade of ovarian cancer with smoking has not been established


Amy Loreen, MD