Biol Trace Elem Res (2014) 162:46–57 DOI 10.1007/s12011-014-0123-4

Comparative Study of Trace Elements in Blood, Scalp Hair and Nails of Prostate Cancer Patients in Relation to Healthy Donors Muhammad Abdul Qayyum & Munir H. Shah

Received: 10 July 2014 / Accepted: 7 September 2014 / Published online: 18 September 2014 # Springer Science+Business Media New York 2014

Abstract Prostate cancer is the most common fatal cancers in men, and exposure to toxic elements is the most important factor in the aetiology for prostate cancer. Selected elements (Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) were analyzed in the blood, scalp hair and nails of prostate cancer patients and counterpart healthy donors by atomic absorption spectrometry. Average concentrations of Cd, Mn, Ni and Pb were found to be significantly higher (pZn>Pb>Cu> Mn>Cr>Cd. Basic statistical parameters for the distribution of trace elements in the blood of controls are also shown in Table 3. Predominantly higher mean concentrations were found for Fe (464.3 μg/g), followed by relatively lower concentrations of Zn (6.571 μg/g), Ni (2.687 μg/g), Pb (2.248 μg/ g) and Cu (1.951 μg/g). The lowest average concentrations were recorded for Cr (0.976 μg/g), Mn (0.895 μg/g) and Cd (0.774 μg/g). On the average basis, trace elements revealed the following order in their concentrations in the blood of controls: Fe>Zn>Ni>Pb>Cu>Cr>Mn>Cd. Relatively larger dispersion in terms of SE was shown by Fe; however, a noticeably higher asymmetry was observed for Zn and Fe in the blood of controls. Overall, most of the elements manifested random distribution in the blood of both donor groups, although comparatively higher dispersion was observed for the patients.

Table 2 Characteristics of the subjects Characteristics

n Age (years) Range Mean Diet (n, %) Vegetarian Nonvegetarian Habitat (n, %) Urban Rural Tobacco use (smoking) (n, %) No use Use Types of prostate cancer (n, %) Adenocarcinoma Squamous cell carcinoma Transitional cell carcinoma Small cell carcinoma Stages of prostate cancer (n, %) Stage I Stage II Stage III Stage IV

Blood

Scalp hair

Nails

Cancer patients

Controls

Cancer patients

Controls

Cancer patients

Controls

74

66

67

67

60

60

32–75 56.77

27–68 47.76

38–72 56.01

31–68 47.13

32–75 55.18

27–68 46.58

43 (58) 31 (42)

38 (58) 28 (42)

39 (58) 28 (42)

42 (63) 25 (20)

37 (62) 23 (38)

36 (60) 24 (40)

36 (49) 38 (51)

36 (55) 30 (45)

33 (49) 34 (51)

33 (49) 34 (51)

32 (53) 28 (47)

35 (58) 25 (42)

43 (58) 31 (42)

37 (56) 29 (44)

39 (58) 28 (42)

39 (58) 28 (42)

34 (73) 26 (27)

32 (53) 28 (47)

42 (57) 14 (19)

– –

37 (55) 12 (18)

– –

34 (57) 10 (16)

– –

10 (14) 08 (10)

– –

10 (15) 08 (12)

– –

09 (15) 07 (12)

– –

19 (26) 20 (27) 12 (16) 23 (31)

– – – –

17 (25) 16 (24) 10 (15) 24 (36)

– – – –

19 (32) 15 (25) 08 (13) 18 (30)

– – – –

50

Qayyum and Shah

Table 3 Statistical distribution parameters for trace element concentrations (μg/g) in the blood, scalp hair and nails of the prostate cancer patients and healthy donors/controls Patients

Blood

Scalp hair

Nails

p value

Controls

Min

Max

Mean

SE

Skew

Min

Max

Mean

SE

Skew

Fe

222.5

2188

850.8

46.52

1.272

106.1

1604

464.3

27.38

3.167

Mn>Cd. Average concentrations of Mn, Ni, Cr and Cd were found to be significantly higher (p0.371 or ≤0.371 are significant at pstage I> stage IV. Mean concentrations of Cu, Mn and Ni were comparable at stage I and stage II, whereas Fe, Zn and Cr concentrations were almost equivalent at stage I and stage IV. Some of the elements (Pb, Cd, Cu, Zn and Fe) exhibited the lowest blood concentrations at stage III. Average concentrations of Fe, Mn, Pb and Cd in the scalp hair were relatively higher at stage IV, while mean concentrations of Ni and Cr were relatively higher at stage III and those of Zn and Cu were relatively higher at stage I. Among the elements, Cu, Mn and Ni concentrations were not significantly different at stage I and stage II. The average concentrations of Pb, Cd, Cr and Zn exhibited almost a similar trend for different stages of the cancer. In case of nail samples, mean concentrations of Cu and Mn were comparatively higher at stage I, while elevated concentrations of Ni, Cr and Cd were observed at stage II. Likewise, elevated concentrations of Zn and Pb were found at stage IV; however, the average concentrations of Fe and Cd were more or less similar at stages I and IV. Mean concentrations of Pb in the nails were nearly comparable at stage I and stage III (Fig. 3). Oxidative stress has been associated with prostate cancer development and progression due to an increase of reactive oxygen species (ROS). However, the precise mechanism whereby ROS participate in the cancer progression is poorly understood. ROS are derived from endogenous and exogenous sources [21]. Increased ROS generation has been associated with tissue injury or DNA damage which are general manifestations of pathological conditions associated with infection, mitochondrial DNA mutations and cellular proliferation [22]. However, the actual effects of oxidative stress may depend on the cellular genetic background, the types of ROS involved, and the extent and time of interference [23]. Various elements (such as, Cr, Ni, Pb, Cd) are reported as catalysts in the oxidative damage of biological systems, and therefore, the toxicity associated with these elements may be due to their ability to generate the free radicals [24, 25]. It is also well established that free radicals are known to react with all

Stage I

Stage II

Stage III

Stage IV

1000

100

10

1

0.1 Fe

Zn

Cu

Mn

Ni

Cr

Cd

Pb

10000 Stage I

Stage II

Stage III

Stage IV

1000 M e ta l L e v e l ( µ g / g ) i n S c a lp H a i r

Comparison Based on Stages of Prostate Cancer

10000

100

10

1

0.1 Fe

Zn

Cu

Mn

Ni

Cr

Cd

Pb

10000 Stage I

Stage II

Stage III

Stage IV

1000 Metal Level (µg/g) in Nails

markedly higher in transitional cell carcinoma patients. Conversely, some of the elements (Zn, Pb, Mn and Ni) exhibited the lowest concentrations in the nails of small cell carcinoma patients.

Qayyum and Shah

100

10

1

0.1 Fe

Zn

Cu

Mn

Ni

Cr

Cd

Pb

Fig. 3 Comparative average concentrations of trace elements (±SE) in the blood, scalp hair and nails of the patients based on cancer stages

components of DNA, thus damaging its bases and the deoxyribose backbone causing mutations in crucial genes, which ultimately may lead to cancer [26, 27]. Exposure to high concentrations of Cd has been suggested to increase prostate cancer risk factor due to its ability to simulate the growth of human prostate epithelial cells even at low concentration and to induce their malignant transformation [28]. It may induce free radical toxicity as a result of reaction with thiols or enzymes, which normally protect against the reactive species. The results of present study were consistent with the other reports in which Cd concentrations in the blood, scalp hair and nails of prostate cancer patients were higher than those of

Comparative Study of Trace Elements of Prostate Cancer Patients

healthy donors [14, 16, 24, 29]. West et al. [30] reported a statistically significant positive association with ingested Cd and prostate cancer risk. Armstrong and Kazantzis [31] and Platz et al. [32] analyzed data from two separate US cohort studies and reported no association between high Cd exposure and prostate cancer risk. Kazantzis et al. [33] found no association between occupational exposure to Cd and prostate cancer mortality in a British cohort. In contrast, Sorahan and Watherhouse [34] observed a statistically significant increased risk of prostate cancer mortality among Ni-Cd alloy workers in the UK. Similarly, Vinceti et al. [35] also reported an elevated Cd concentration in the nails of prostate cancer patients in comparison with the healthy subjects. Epidemiological studies showed that exposure to Ni and its compounds produced a high risk of various types of cancer [24, 36–38]. Sorahan and Watherhouse [34] reported a statistically significant increased risk of prostate cancer mortality with relatively high occupational Ni exposure. Average concentrations of Ni and other elements (Cu and Fe) in the blood of prostate cancer patients were reported to be higher than those of controls [39]. Concentration of Cr was also reported to be significantly higher in prostate cancer patients than that in normal subjects [40]. In a previous study, the blood, hair and nail Pb concentrations were reported to be significantly higher in prostate cancer patients than those in controls [41]. Generally, Mn is not considered carcinogenic to humans [42]; however, Prasad et al. [43] reported that Mn toxicity damages the brain and may have caused prostate cancer. Kwiatek et al. [44] reported an increase of Mn, Ni and Co concentrations in prostate cancer. Zinc plays a key role in maintaining antioxidant defences and DNA repair systems, failure to which may result in human carcinogenesis [45]. It has been known that Zn concentration in the prostate gland is much higher than that in any other organ, which suggested that Zn may play a role in prostate function and health. Zinc is well known to induce production of metallothionein, which is very rich in cysteine, and this is an excellent scavenger of hydroxyl radical. Epidemiological studies provided contradictory findings on the effectiveness of Zn in prevention against prostate cancer; there were studies that showed that Zn reduces the risk of developing prostate cancer [46], while others showed that there were neither beneficiary nor potential adverse effects of Zn on prostate cancer risk [47]. However, many studies showed that Zn deficiency was considered as possible risk factor for prostate cancer [48]. It is notable that the hair Zn concentration between patients with malignancy was also significantly lower than that in normal patients [1, 4]. In the present study, Zn concentrations in the blood, scalp hair and nails were considerably lower in prostate cancer patients than those in healthy donors. It is important to note that oxidative stress markers are prognostically important in prostate cancer, but these biomarkers are not analyzed in the present study. Although

55

accumulation of some elements has been clearly demonstrated in the cancer patients, it is still unclear whether this is a consequence of the disease or a need for its development. It was also observed in the present study that socioeconomic factors also play a role in higher mortality rates in patients, such as poor nutrition, irregular screening, late diagnosis and unequal access to health care. The cost factor of cancer treatment is also very high. The local hygiene centre facilities are poor in Pakistan, and there are no any routine monitoring and screening carried out for those people living in small towns. Trace element analysis of the cancer patients could become a powerful diagnostic tool. Considering risk assessment of metal toxicology, future research should be focused on the relevance of respective mechanisms in experimental animals and exposed humans, especially with respect to effective metal concentrations. Further study having a large number of subjects is warranted to more clearly define the risks associated with specific exposures with different histological types of prostate cancer. A better understanding of the molecular basis for the development and progression of prostate cancer is needed. The fact that the risk factors of prostate cancer are uncertain provides additional setbacks and halts the search for preventative measures that could benefit for potential patients. Although, further studies are required in this area, these reports, nevertheless, raised concern for potential detrimental outcomes of long-term exposure of trace elements in human.

Conclusions The concentration of trace elements in the blood, scalp hair and nails of the cancer patients in comparison with that in the controls were considerably divergent. In the blood and scalp hair of prostate cancer patients, Pb, Cd, Ni, Mn and Fe were significantly higher compared to those of the controls, but the concentration of Zn was considerably lower in the patients than that in the controls. The average concentrations of Fe, Zn and Cu were appreciably higher in the scalp hair and nails of controls; nonetheless, some of the elements (Cd, Ni and Mn) were significantly higher in the nails of patients than those of controls, thus indicating the imbalance of these elements in the patients. Likewise, the average concentration of Cr was not significantly different in the blood, scalp hair and nails of patients and controls. Trace elements also exhibited significant disparities in the blood, scalp hair and nails of the patients and controls based on abode, food habits, smoking habits, cancer types and stages. The correlation study revealed appreciably different mutual variations of the elements in the blood, scalp hair and nails of the two groups. CA revealed different apportionment mechanisms of trace elements in the blood, scalp hair and nails of the cancer patients and controls which

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evidenced that the carcinogenic processes were significantly affecting the trace element balance in humans. Acknowledgments The funding by Higher Education Commission, Government of Pakistan, to carry out this project is thankfully acknowledged. We are also grateful to the administration of Nuclear Oncology & Radiotherapy Institute (NORI), Islamabad, Pakistan, for their invaluable help during sample collection. Technical and financial help by Quaid-iAzam University, Islamabad, Pakistan, to execute this project is also acknowledged.

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