180P - An HLA-diet-oriented system unveiling organ-specific occurrence of multiple primary cancers (MPC) with prevention strategy: A large cohort study of 47,550 cancer patients

Background

Along with the prolonged survival of cancer patients in recent years comes another dilemma, multiple primary cancers (MPC), which rob cancer patients of their privilege to optimal treatments. Nonetheless, understanding the hereditary and postnatal predisposition of MPC is still in its infancy.

Methods

We included 47,550 cancer patients in UK Biobank. Hazardous and protective HLA alleles concerning MPC were recognized leveraging stepwise logistic regression, which was further validated by log-rank test and Cox proportional hazard model. Logistic regression was used to investigate the organ-specific association between HLA and MPC. Cox proportional hazard model was used to explore potential interventions.

Results

Two protective (DPA1*02:02 and DRB1*04:03) and four hazardous (A*26:01, A*24:03, DPB1*20:01 and DQB1*06:01) HLA alleles are significantly associated with MPC risk for male, whereas one protective (DRB5*01:01) and four hazardous (A*03:02, DRB1*08:03, DQB1*05:04, and DPB1*11:01) for female. Compared with patients without MPC-related HLA alleles, both male and female patients carrying protective HLA alleles have lower risk of MPC (HR, 0.67 [95% CI, 0.53-0.83] and HR, 0.84 [95% CI, 0.73-0.97], respectively), while those carrying hazardous HLA alleles have higher risk of MPC (HR, 1.31 [95% CI, 1.09-1.57] and HR, 1.55 [95% CI, 1.25-1.93], respectively). HLA alleles are associated with organ-specific MPC occurrence. Lower animal fat intake subsided (HR, 0.46 [95% CI, 0.26-0.82]) while unqualified vegetable fat intake increased MPC risk (HR, 2.23 [95% CI, 1.22-4.07]) for male cancer patients carrying hazardous HLA alleles. Lower free sugar intake subsided the risk of MPC for female patients carrying hazardous HLA alleles (HR, 0.34 [95% CI, 0.15-0.74]).

Conclusions

HLA alleles might help to understand the predisposition and organ-specific incidence of MPC. Intervention on diet could counteract the risk.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Zhongyi Dong.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.