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David S. Ettinger, MD, FACP, FCCP


AACR 2022: Could Estrogen Derivatives Be Linked to Lung Cancer in Never-Smokers?

By: Joseph Fanelli
Posted: Thursday, April 14, 2022

Findings presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 2696/11) suggest that C4 estrogen derivatives may contribute to oncogene-driven lung tumors, a possible explanation as to the increase in the numbers of non-smokers with lung cancer in the United States. Targeting the enzyme CYP1b1 could be of preventive and therapeutic interest for future studies, according to study presenter J. Nicholas Bodor, MD, PhD, MPH, of Fox Chase Cancer Center, Philadelphia, and colleagues. To validate these early findings in a larger cohort, recruitment of study participants is ongoing.

“We are seeing more and more patients in our clinics diagnosed with lung cancer who have no smoking history,” said Dr. Bodor in a Fox Chase press release. “We found that the putative carcinogen 4-OHE appears to be higher in the urine of patients with EGFR and ALK lung cancers as compared to cancer-free individuals.”

In this study, the resulting levels of estrogen derivatives were correlated with genotypic variants in the estrogen-metabolizing enzymes CYP1B1 and COMT. The authors recruited 34 patients with EGFR-mutated non–small cell lung cancer (NSCLC) and 10 patients with ALK-mutated NSCLC from the recently established Never-Smokers Lung Cancer Clinic at the Fox Chase Cancer Center. All the patients were at least 50 years old. Postmenopausal White women with no smoking history were used as control subjects (17 patients).

A preliminary investigation of the E1 metabolic pathway suggested that patients with EGFR- and ALK-positive NSCLC had higher ratios of 4-OHE1 to 2-OHE1 derivatives, compared with cancer-free subjects. Among the patients with NSCLC, those with high activity of the Leu432 variant of CYP1B1 were more likely to have higher ratios of 4-OHE1 to 2-OHE1 as compared with patients with low activity of the Val/Val genotype.

Disclosure: For a full disclosure of the study authors, visit

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