OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.
DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.
RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation.
CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade.
PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.
METHODS: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.
RESULTS: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2=1.35 (95% CI 1.04-1.76), Ptrend=0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet=0.98) or baseline HT use (Phet=0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend=0.06 vs Ptrend=0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors<4 years compared to ≥4 years after blood donation (Ptrend=0.01 vs Ptrend=0.63; Phet=0.04) and among nulliparous women compared to parous women (Ptrend=0.03 vs Ptrend=0.15; Phet=0.07).
CONCLUSIONS: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.
RESULTS: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.
CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.
MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.
RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.
CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.
OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.
DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.
RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).
CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.
PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.
METHODS: We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data.
RESULTS: Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer.
CONCLUSION: Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels.
MATERIALS AND METHODS: This study included a total of 240 matched cases and controls where subjects were selected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, α-tocopherol and β-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and food frequency questionnaire (FFQ) respectively.
RESULTS: It was found that results from the two methods applied did not correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels of retinol and α-tocopherol among cases (0.177±0.081, 1.649±1.670μg/ml) were significantly lower than in controls (0.264±0.137, 3.225±2.054μg/ml) (p<0.005). Although serum level of β-carotene among cases (0.106±0.159 μg/ml) were lower compared to controls (0.134±0.131μg/ml), statistical significance was not observed. Logistic regression analysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and α-tocopherol (OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas no relationship was observed between β-carotene and oral cancer risk.
CONCLUSIONS: High serum levels of retinol and α-tocopherol confer protection against oral cancer risk.
METHODS: This hospital based case control study conducted in the Western part of Nepal covered a total of 93 cancer patients with or without alcohol intake and smoking habits, along with 94 age, sex and habit-matched individuals serving as controls. Plasma thiobarbituric acid reacting substances (TBARS), total antioxidant activity (TAA), vitamin C, α-tocopherol and erythrocyte reduced glutathione (GSH) were estimated and compared.
RESULTS: The TBARS level was found to be significantly higher (p≤0.001) in all types of cancer patients when compared to controls, being aggravated in alcoholics with a smoking habit. No statistical significance (p≥0.05) was observed in the level of vitamin C and α-tocopherol. GSH and TAA level were significantly decreased (p≤0.001) in all the groups except those who consumed both branded as well as homemade alcohol and non-alcoholics without smoking habit.
CONCLUSION: Alcohol, irrespective of its commercial brand, increases oxidative stress in all types of cancer patients. This is even higher when alcohol intake is combined with a smoking habit. Decreased TAA and GSH are major risk factors for cancer development.