Metabolism biomarkers measured before prostate cancer diagnosis and second primary tumours: a prospective study in the Swedish AMORIS cohort.


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Cecilia Bosco1,Hans Garmo1,Niklas Hammar2,Göran Walldius2,Ingmar Jungner2,Håkan Malmström2,Lars Holmberg2
1King's college london,2Karolinska Institutet

Abstract

Background

Due to advances in detection and treatment the number of men living with prostate cancer (PCa) is increasing. As a result, men with PCa are at an increased risk of a second primary tumour (SPT). Few studies have investigated potential biochemical mechanisms linking PCa with the occurrence of SPTs.

Method

From the Swedish AMORIS cohort, we selected all men diagnosed with PCa between 1996 and 2011 who had at least one of the five biomarkers of interest (glucose, fructosamine, triglycerides, total cholesterol, gamma-glutamyl transferase (GGT)) measured on average 16 years before PCa diagnosis and whose tumour characteristics were registered in the National Prostate Cancer Register (n=14,021). We also used information on sociodemographic characteristics, diabetes, and time between blood test and PCa diagnosis. Missing data was imputed and multivariate Cox proportional hazards models were used to determine the hazard ratios (HR) for risk of SPTs by levels of the five biomarkers of interest. Subtypes of SPTs were also evaluated as were the potential effects of PCa stage and treatment on development of SPTs.

Results

A total of 1,035 SPTs were diagnosed during a median follow-up time of 5 years.  There was a positive association with SPTs for triglycerides, total cholesterol, and GGT when comparing abnormal levels with normal levels (according to established clinical cut-offs) (HR: 1.29, 95%CI: 1.09-1.53; 1.38, 1.17-1.62; 1.4, 1.11-1.75, respectively). No associations with fructosamine were observed. Stratification by PCa treatment did not change these associations. A positive association was observed between triglycerides, total cholesterol, and SPTs of digestive organs, genitourinary, rectal and skin. High levels of GGT were also associated with SPTs of digestive organs and respiratory system.

Conclusion

Biomarkers of lipid metabolism and GGT measured before PCa diagnosis were positively associated with occurrence of a SPT. Our observations suggest a potential common biochemical background between PCa and some SPTs.