Abstract
Insulin‐like growth factor‐I (IGF‐I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF‐I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow‐up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadal‐associated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09–1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92–2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37–0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35–0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF‐I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.
Highlights
Prostate cancer is the second most common cancer in men worldwide.[1]
Men diagnosed with acromegaly had an increased risk of incident prostate cancer, while men diagnosed with diseases characterised by low testosterone had a lower risk of prostate cancer mortality
Compared to the reference cohort, acromegaly was associated with a 33% increased risk of being diagnosed with prostate cancer (HR = 1.33, 95% confidence intervals (CIs) 1.09–1.63; p = 0.005), and a 44% increased risk of prostate cancer death (HR = 1.44, 95% CI 0.92–2.26; p = 0.11; Fig. 1)
Summary
Prostate cancer is the second most common cancer in men worldwide.[1] Established risk factors include age, family history, ethnicity and genetic factors.[2] there are large differences in global incidence rates, little is known regarding potentially modifiable risk factors. Data from an international pooled individual-level meta-analysis of prospective studies have shown that high circulating insulin-like growth factor-I (IGF-I). The incidence rates of prostate cancer vary globally, little is known about modifiable risk factors. Previous studies have shown insulin-like growth factor-I (IGF-I) and testosterone may be related to prostate cancer risk. Men diagnosed with acromegaly (characterised by high IGF-I) had an increased risk of incident prostate cancer, while men diagnosed with diseases characterised by low testosterone had a lower risk of prostate cancer mortality. The findings support the role of IGF-I and testosterone in prostate cancer pathogenesis
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