Plasma prolactin and prostate cancer risk: A prospective study

Abstract

Prolactin, a pituitary peptide hormone with multiple effects, stimulates prostate growth in experimental models. In humans, prolactin receptors are present in the prostate and are particularly abundant in pre-cancerous lesions. This suggests that prolactin could also be involved in the development of prostate cancer. In this study, we tested the hypothesis that elevated levels of circulating prolactin are associated with an increase in prostate cancer risk. We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort using plasma samples collected from 29,560 men at a health survey. We measured prolactin in plasma from 144 men who had a diagnosis of prostate cancer after a median follow-up time of 4 years after health survey and from 289 controls matched for age and date of recruitment. Risk was not associated with plasma prolactin levels in univariate regression analysis. Odds ratios of prostate cancer for increasing quartiles of prolactin were 1.0, 0.92 (95% CI 0.51-1.65), 0.82 (0.45-1.51) and 0.85 (0.49 -1.47). Relative risk estimates remained unchanged after adjustments for height and weight or for plasma levels of testosterone, sex hormone-binding globulin, Prolactin, a pituitary peptide hormone, stimulates prostate growth in experimental studies. In vitro, prolactin induces proliferation and antagonises apoptosis in prostate organ culture 1 and in some tumour cell lines 2,3 but not in others. 3,4 In vivo studies have consistently shown that hyperprolactinaemia induces prostate proliferation 5-7 and differentiation 8 in the rat prostate, and prolactin stimulated growth of the Dunning R3327 PAP tumour. 5 Wennbo et al. 9 showed in a transgenic mouse model that mice over-expressing prolactin had a 20-fold increase in prostate weight compared with control animals. Furthermore, the development of inflammation 10 and dysplasia 11 of the prostate in rats chronically treated with androgen and oestrogen combinations is mediated by increased plasma prolactin.In humans, receptors for prolactin are expressed in the prostate, 1 and the expression is particularly elevated in high-grade prostate intra-epithelial cell neoplasia (PIN), a precursor of prostate cancer. 12 Local production of prolactin has also been demonstrated in the prostate. 1 Plasma prolactin rises sharply at puberty and continues to increase in parallel with the age-related increase seen in the incidence of benign prostatic hyperplasia and prostate cancer. 13 Collectively, these experimental and chronobiological results suggest that increased levels of circulating prolactin induce prostate growth and possibly prostate tumour growth. However, epidemiological data concerning prolactin and prostate cancer are sparse and inconclusive: several small case-control studies 14 -17 and 2 prospective cohort studies 18,19 have not shown a consistent association between circulating prolactin concentrations and prostate cancer risk. To further investigate the relationship between circulating prolactin levels and prostate cancer dev...

Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review

“…97 A similar result was obtained in the Northern Sweden Health and Disease Study (NSHDS), another large prospective cohort. 98 In this second cohort study, the increase in risk was particularly strong in men who provided their blood sample at age 40 ± 50, and who developed a prostate tumour below age 60 (relative risks and 95% con®dence intervals of 1.00, 2.97 (0.84 ± 10.49), and 4.30 (1.19 ± 15.50), for tertiles of IGF-1). Furthermore, prostate cancer risk was positively related to total circulating IGF-1 in two case-control studies (210 and 52 cases, respectively), 99,100 but not in a third, small prospective study that included only 45 incident cases of prostate cancer.…”

“…Furthermore, in the prospective NSHDS there was no signi®cant association of prostate cancer risk with direct measurements of fasting plasma insulin, IGFBP-1 or IGFBP-2. 98 Regarding adult body height, many studies do show a positive association, although very modest, with prostate cancer risk (Table 3). A meta-analysis of the prospective studies showed a signi®cant increase in prostatic cancer risk of about 20 ± 25%, comparing upper and lower quartiles of height, and a similar increase was shown for the case ± control studies (results not shown).…”

Hormonal regulation of H19 gene expression in prostate epithelial cells

“…A high blood concentration of PRL in some prostate cancer patients has been reported (Harper et al 1976, Horti et al 1998. Although Stattin et al (2001) have established only a slight correlation between hyperprolactinemia and increased risk of prostate cancer in men, Ben-Jonathan et al (2002) recently reported that PRL increases prostate weight and promotes development of dysplasia and adenocarcinoma of the dorsolateral lobe of the rat prostate. The latter group suggested that PRL might contribute to early carcinogenesis by activating several target genes.…”

New concepts in prolactin biology

“…The largest study published to date involved the Northern Sweden Health and Disease Cohort study, which involved follow-up of nearly 30 000 men, including 144 subjects diagnosed with prostate cancer (Stattin et al 2001). This study concluded that there was no correlation between PRL levels and cancer risk.…”