Multiple reproductive factors may leave women more vulnerable to lung cancer than men. A prospective population study of nearly 275,000 women in the UK Biobank found that early age at menarche, early age at menopause, shorter reproductive span, and earlier age of first live birth are all associated with increased risk of developing new onset lung cancers over the succeeding 12 years.
Multiple epidemiologic studies have found that women are at increased risk of lung cancer compared to men, said Yan Zhang, MD, PhD, Professor of Respiratory and Critical Care Medicine, Xiangya Hospital of Central South University, Changsha, China. The latest report from the Union for International Cancer Control, GLOBOCAN 2020, reported that not only does lung cancer remain the leading cause of cancer deaths worldwide, but that women who do not smoke have a 3-fold higher risk of developing lung cancer compared to men who do not smoke.
“Hormonal and reproductive factors were thought to be involved in the occurrence of lung cancer in women, however findings over the last decade have been far from consistent,” Dr. Zhang said “We think different study designs, different populations, and different follow-up periods account for the differences. This is the longest follow-up period and one of the largest cohorts to date.”
Dr. Zhang reported the results of the UK-based study during the 2023 World Conference on Lung Cancer on Monday, September 11. The session, Lung Cancer Prevention in the New Millennium, can be viewed on demand by registered WCLC attendees through December 31.
Researchers followed 273,190 women enrolled in the UK Biobank for a median of 12 years and found 1,182 cases of new onset lung cancer. Women who were diagnosed with lung cancer were older, had a lower educational background, and were more likely to smoke than other women in the database, Dr. Zhang reported.
Compared to women who reached menarche at age 13, women who experienced menarche at age 11 or younger had a 22% increased risk for lung cancer, she said. Additionally, women who reached menarche at age 12 had a 7% increased risk. Menarche at 14 was associated with a slightly reduced risk—0.96%—of developing lung cancer, however, those who reached menarche at age 15 or later had a 3% increased risk.
Age at menopause showed similar trends. Based on a reference age of 50-52 years, menopause at age 46 or before increased lung cancer risk by 49% while menopause at ages 47-49 years was associated with a 42% increase in risk. Women who experienced menopause slightly later—at 53-54 years of age—had a 19% increase in risk, while those who reached menopause at age 55 or later had slightly lower risk—0.84%) compared to the reference group.
Looking at the data another way, women who had a reproductive span of 32 years or less carried a 42% increased risk for lung cancer compared to the reference group with a reproductive span of 36-39 years, Dr. Zhang said. A reproductive span of 33-35 years was associated with a 24% increase in risk, a span of 40-42 years with a 1% increase in risk, and a span greater than 43 years was associated with a slight reduction in risk compared to the reference group (0.84%).
Among parity-related factors, age of first live birth showed a similar association with lung cancer risk. Based on 26-30 years as a reference, having a first live birth before age 20 carried a 63% increased risk for lung cancer. A first live birth between ages 21-25 was associated with a 31% increased risk, ages 31-35 with a 0.89% risk, and at age 36 or later with a 3% increased risk.
Hormone dysfunction may also be a factor in lung cancer risk. Oophorectomy was associated with a 25% increased risk for lung cancer. Hysterectomy, hormone replacement therapy (HRT), HRT duration, and oral contraceptive use also increased risk. However, Dr. Zhang said it is difficult to tease out individual contributors because many women had multiple factors, such as hysterectomy plus HRT.
“We can conclude that early menarche, early menopause, and early age at first live birth are all associated with increased risk for lung cancer,” Dr. Zhang said. “These findings support the importance of including reproductive factors in lung cancer screening programs.”