Research Paper Volume 13, Issue 3 pp 3712—3725

Advanced paternal age and risk of cancer in offspring

Yangyang Sun1, *, , Xu Li1, *, , Wei Jiang2, *, , Yuanming Fan1, , Qiong Ouyang1, , Wei Shao3, , Raphael N. Alolga1, , Yuqiu Ge4, , Gaoxiang Ma1, ,

  • 1 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
  • 2 Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, China
  • 3 Department of Science and Technology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
  • 4 Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China
* Equal contribution

Received: July 17, 2020       Accepted: November 15, 2020       Published: December 19, 2020
How to Cite

Copyright: © 2021 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Many risk factors of cancer have been established, but the contribution of paternal age in this regard remains largely unexplored. To further understand the etiology of cancer, we investigated the relationship between paternal age and cancer incidence using PLCO cohort. Cox proportional hazards models were performed to assess the association between paternal age and the risk of cancers. During follow-up time (median 11.5 years), 18,753 primary cancers occurred. Paternal age was associated with reduced risk of cancers of the female genitalia (HR, 0.79; 95%CI, 0.66-0.94; P = 0.008) as well as cancers of the respiratory and intrathoracic organs (HR, 0.78; 95%CI, 0.63-0.97; P = 0.026). The association was stronger for lung cancer (HR, 0.67; 95%CI, 0.52-0.86; P = 0.002). The subgroup analysis suggested that age, gender, smoking and BMI were related to the decreased cancer incidence of the respiratory and intrathoracic organs, lung and the female genitalia. Positive linear associations were observed between paternal age and cancer incidence of the female genitalia, respiratory and intrathoracic organs and the lungs. These findings indicate that advanced paternal age is an independent protective factor against various cancers in offspring.


PLCO: Prostate, Lung, Colorectal, and Ovarian; HR: hazard ratio; CI: confidence interval; IARC: International Agency for Research on Cancer; BMI: body mass index; TL: telomere length; LTL: leukocyte telomere length; BQ: baseline questionnaire; SQ: supplemental questionnaire; DHQ: diet history questionnaire; ICD-O-3: International Classification of Disease for Oncology, third edition.