Circulating leukocyte telomere length and risk of overall and aggressive prostate cancer.

BACKGROUND: Recent large-scale prospective studies suggest that long telomeres are associated with an increase cancer risk, counter to conventional wisdom. METHODS: To further clarify the association between leukocyte telomere length (LTL) and prostate cancer, and assess genetic variability in relation to both LTL and prostate cancer, we performed a nested case-control study (922 cases and 935 controls). The participants provided blood in 1993-1995 and were followed through August 2004 (prostate cancer incidence) or until 28 February 2013 (lethal or fatal prostate cancer). Relative LTL was measured by quantitative PCR and was calculated as the ratio of telomere repeat copy number to a single gene (36B4) copy number (T/S). Genotyping was performed using the TaqMan OpenArray SNP Genotyping Platform. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of all prostate cancer and subtypes defined by Gleason grade, stage and lethality (metastasis or death). RESULTS: We observed a positive association between each s.d. increase in LTL and all (multivariable-adjusted OR 1.11, 95% CI: 1.01-1.22), low-grade (OR 1.13, 95% CI:1.01-1.27), and localised (OR 1.12, 95% CI:1.01-1.24) prostate cancer. Associations for other subtypes were similar, but did not reach statistical significance. In subgroup analyses, associations for high grade and advanced stage (OR=2.04, 95% CI 1.00-4.17; Pinteraction=0.06) or lethal disease (OR=2.37, 95% CI 1.19-4.72; Pinteraction=0.01) were stronger in men with a family history of the disease compared with those without. The minor allele of SNP, rs7726159, which has previously been shown to be positively associated with LTL, showed an inverse association with all prostate cancer risk after correction for multiple testing (P=0.0005). CONCLUSION: In this prospective study, longer LTL was modestly associated with higher risk of prostate cancer. A stronger association for more aggressive cancer in men with a family history of the disease needs to be confirmed in larger studies.

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study.

BACKGROUND: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated. METHODS: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases). RESULTS: Mean dietary cadmium exposure was 19 µg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers. CONCLUSION: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

Dietary cadmium exposure and risk of epithelial ovarian cancer in a prospective cohort of Swedish women.

BACKGROUND: The proposed cadmium-induced oestrogen mimicking effects in reproductive tissues, suggest a role of this widespread food contaminant in the development of hormone-dependent malignancies. METHODS: We prospectively evaluated the association between tertiles of dietary cadmium exposure and epithelial ovarian cancer in 60,889 women from the population-based Swedish Mammography Cohort. Dietary cadmium was estimated using a food-frequency questionnaire at baseline (1987-1990) and in 1997. Multivariable-adjusted rate ratios (RR) were evaluated using Cox proportional hazards models. RESULTS: During a mean follow-up of 18.9 years (1,149,470 person-years), we identified 409 incident cases of epithelial ovarian cancer, including 215 serous, 27 mucinous, 62 endometrioid and 12 clear cell tumours. We found no association between dietary cadmium exposure and the risk of ovarian cancer. Compared with the lowest tertile of cadmium exposure, the multivariable-adjusted RR for the highest tertile was 0.90 (95% confidence interval (CI): 0.71-1.15) for total epithelial ovarian cancer. Likewise, no association was observed in subtypes modelled with continuous dietary cadmium exposure; multivariable RR for each 1 µg per day increment of cadmium: 0.97 (95% CI: 0.93-1.02) for serous tumours, 0.94 (95% CI: 0.82-1.07) for mucinous tumours and 1.00 (95% CI: 0.92-1.08) for endometrioid and clear cell tumours. CONCLUSION: Our study suggests that dietary cadmium exposure is not likely to have a substantial role in ovarian cancer development.