The relationship of human chorionic gonadotropin beta (hCGβ) expression and luteinizing hormone gene mutation (vLH) with prostate cancer in population groups of multi-ethnic origin

Abstract

Data have shown that Black men have the highest incidence and mortality from prostate cancer in the world. Even after adjusting for stage at diagnosis, black men have higher mortality rates than white men (Freedland, 2005). One of the postulated theories is the elevated androgen level in African-Caribbean men (Mohler, 2004, Abdelrahaman, 2005).

In addition, it has been shown that the prevalence of prostatic carcinoma in the United Arab Emirates (UAE), like other Arabian Gulf and Asian countries, is very low compared to Western countries (Ghafoor, 2003).

The beta subunit of the human chorionic gonadotropin (hCG) has been associated with aggressive cancers, including prostate cancer (Rao, 2004; Weissbach, 1999; Dirnhofer, 1998; Dirnhofer, 2000; Noeman, 1994; Crawford et al., 1998). It has been suggested that it may act as an autocrine growth factor by inhibiting apoptosis, mediated by inhibition of the transforming growth factor  (TGF) receptor complex (Iles, 2007).

A common genetic variant of Luteinizing Hormone (LH) has been identified. The prevalence of this variant LH (vLH) allele has been estimated worldwide as a carrier frequency of 0% to 53% of Caucasians and is known to be more active than the wild-type protein (Elkins, 2003). In addition to its well-known physiological role in androgen metabolism, its role in prostate tissue is possibly through the conversion of testosterone into dihydrotestosterone (DHT), thus potentiating the androgen effect of prostatic tissue (Douglas, 2005).

Archival prostate tissue samples –including benign prostate hyperplasia (BPH) and prostate cancer- were obtained from Caucasians (n=118, UK), African-Caribbean men (n=92, UK) and men from the UAE (Middle Eastern Caucasoids) (n=148, UAE). Of those with prostate cancer, seventy-one had organ-confined disease, thirty had locally advanced disease and seventeen had metastatic disease at presentation.

hCG and vLH were studied using Immunohistochemistry (IHC) for the former and Nested Polymerase Chain Reaction (PCR) for the latter.

It was found, using Kruskal-Wallis analysis, that the expression of hCG in the African-Caribbean group was significantly higher than the Caucasians and the Middle East group (African-Caribbean group versus Middle East: P = 0.0009, African-Caribbean group versus Caucasians: P = 0.0082, Middle East versus Caucasians: P = 0.653). However, there was no significant association between the positive expression of hCG and survival (P = 0.8881).

Regarding the vLH, it was found that the presence of the vLH in the three ethnic groups is extremely rare (0.011%) in BPH and prostate cancer patients.

These findings show that there is a significant association of the hCG expression with the African-Caribbean men; a group known to have a higher baseline testosterone levels (Mohler, 2004; Abdelrahaman, 2005). This may be mediated through a possible role of hCG  in cross-interaction with TGF beta receptor, leading to inhibition of apoptosis (Iles, 2007), or with LH beta receptor, increasing the conversion of testosterone into its active metabolite; dihydrotestosterone with ultimate increase in the risk of development of prostate cancer (Douglas, 2005).