| Title: | HLA diversity unveils susceptibility and organ-specific occurrence of second primary cancers: a prospective cohort study |
| Journal: | BMC Medicine |
| Published: | 8 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39380026/ |
| DOI: | https://doi.org/10.1186/s12916-024-03676-6 |
Publication 13261
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Abstract
BackgroundUp to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence.MethodsWe analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles.ResultsDuring a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59-0.89; females: HR 0.81, 95% CI 0.70-0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03-1.56; females: HR 1.35, 95% CI 1.07-1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females.ConclusionsThese results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC.</p>
14 Keywords
- Adult
- Aged
- Alleles
- Female
- Genetic Predisposition to Disease
- HLA Antigens
- Humans
- Incidence
- Male
- Middle Aged
- Neoplasms, Second Primary
- Polymorphism, Single Nucleotide
- Prospective Studies
- United Kingdom
16 Authors
- Zi-Xuan Rong
- Wei Wei
- Qin Zeng
- Xiao-Ting Cai
- Yuan-Yuan Wang
- Jian Wang
- He-San Luo
- Lu-Shan Xiao
- Jia-Run Lin
- Xue Bai
- Yan-Pei Zhang
- Duan-Duan Han
- Zhong-Yi Dong
- Wei Wang
- De-Hua Wu
- Si-Cong Ma
1 Application
| Application ID | Title |
|---|---|
| 92668 | Development and validation of enhanced prediction models based on polygenic analysis and clinical factors for chronic diseases |
Enabling scientific discoveries that improve human health