Association of serum α-tocopherol, ß-carotene, and retinol with liver cancer incidence and chronic liver disease mortality.

BACKGROUND: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, ß-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. METHODS: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. RESULTS: Higher ß-carotene and retinol levels were associated with less liver cancer (ß-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (ß-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of ß-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. CONCLUSIONS: Our findings suggest that higher concentrations of ß-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.

Effects of α-tocopherol and ß-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

BACKGROUND: Recent data suggest the possible benefits of α-tocopherol and ß-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. METHODS: We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) ß-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes. RESULTS: Supplemental α-tocopherol, ß-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. CONCLUSIONS: Long-term supplemental α-tocopherol or ß-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

Pigmentation-related phenotypes and risk of prostate cancer.

BACKGROUND: Solar ultraviolet radiation exposure has been inversely related to prostate cancer incidence and mortality, possibly mediated through vitamin D status. Pigmentation-related traits influence endogenous vitamin D synthesis and may alter risk of prostate cancer. METHODS: We examined prostate cancer in relation to hair and eye colour, and skin phototype in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Incident cancer was diagnosed in 1982 out of 20 863 men. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazards models. RESULTS: Prostate cancer risk did not differ by eye colour or skin phototype. Men with naturally red hair were significantly less likely to develop prostate cancer (HR=0.46, 95% CI 0.24-0.89) than men with light brown hair (reference). CONCLUSION: The red hair phenotype, which results from polymorphisms in the melanocortin-1-receptor (MC1R) gene, is associated with lower risk of prostate cancer. This pigmentation-related trait may influence prostate cancer development either directly, through genetic effects or regulatory mechanisms related to MC1R, another nearby gene, or other pigmentation genes, or indirectly, through associations with other exposures such as sunlight or vitamin D status.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

BACKGROUND: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. METHODS: We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. RESULTS: Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. CONCLUSION: These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Influence of vitamin D binding protein on the association between circulating vitamin D and risk of bladder cancer.

BACKGROUND: There is little research investigating the role of vitamin D binding protein (DBP) in the association between 25-hydroxyvitamin D (25(OH)D) and disease risk. METHODS: Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, 250 bladder cancer cases were randomly sampled and matched 1:1 to controls on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer were estimated by quartiles of DBP (measured by ELISA), 25(OH)D and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Analyses were also conducted stratifying 25(OH)D by DBP (median split) and vice versa. RESULTS: We found no direct association between circulating DBP levels and bladder cancer risk (P-trend=0.83). The inverse association between 25(OH)D and bladder cancer risk was unchanged after adjustment for DBP (Q4 vs Q1 OR=0.61, 95% CI=0.36-1.05; P-trend=0.04), and was stronger among men with lower DBP (low DBP: 25(OH)D Q4 vs Q1 OR=0.47, 95% CI=0.23-1.00; high DBP: 25(OH)D Q4 vs Q1 OR=0.83, 95% CI=0.40-1.75; P for interaction=0.11). CONCLUSION: Our findings provide additional support for an aetiologic role for vitamin D in bladder cancer and suggest that free, rather than total, circulating vitamin D may be a more relevant exposure when examining bladder and, perhaps, other cancers.

Carbohydrate substitution for fat or protein and risk of type 2 diabetes in male smokers.

BACKGROUND/OBJECTIVES: We examined the associations between carbohydrate substitutions (total; low-, medium-, high-glycemic index (GI) carbohydrates) for fat or protein and risk of type 2 diabetes. SUBJECTS/METHODS: The cohort comprised 25,943 male smokers among whom 1098 diabetes cases were identified from a national register during a 12-year follow-up. Diet was assessed by a validated food frequency questionnaire. The relative risks (RR) and confidence intervals (CI) for diabetes were analyzed using Cox proportional hazard modeling, and multivariate nutrient density models were applied to examine the associations between substitutions of macronutrients and diabetes risk. RESULTS: The risk of diabetes was lower when fat or protein was replaced with an isoenergetic amount (2% of energy intake) of carbohydrates, the multivariate RRs were 0.96 (95% CI: 0.94, 0.99) and 0.85 (95% CI: 0.80, 0.90), respectively. The lower risks were due to replacing saturated plus trans fatty acids, and meat, milk or plant protein with carbohydrates, respectively. Low-, medium- or high-GI carbohydrates did not associate with lower diabetes risk when replacing fat or fatty acids, except when total fat was replaced with medium-GI carbohydrates. Low-, medium- and high-GI carbohydrates had similar inverse associations with diabetes risk when they replaced total, meat or milk protein. CONCLUSION: Higher carbohydrate intake at the expense of fat, attributable to trans and saturated fatty acids, or protein was associated with decreased diabetes risk. Replacing fat or protein with lower-GI carbohydrates was not more beneficial than replacing it with higher-GI carbohydrates.

Dietary acrylamide exposure among Finnish adults and children: the potential effect of reduction measures.

A deterministic exposure assessment using the Nusser method that adjusts for within-subject variation and for nuisance effects among Finnish children and adults was carried out. The food consumption data covered 2038 adults (25-74 years old) and 1514 children of 1, 3 and 6 years of age, with the data on foods' acrylamide content obtained from published Finnish studies. We found that acrylamide exposure was highest among the 3-year-old children (median = 1.01 µg kg(-1) bw day(-1), 97.5th percentile = 1.95 µg kg(-1) bw day(-1)) and lowest among 65-74-year-old women (median = 0.31 µg kg(-1) bw day(-1), 97.5th percentile = 0.69 µg kg(-1) bw day(-1)). Among adults, the most important source of acrylamide exposure was coffee, followed by casseroles rich in starch, then rye bread. Among children, the most important sources were casseroles rich in starch and then biscuits and, finally, chips and other fried potatoes. Replacing lightly roasted coffee with dark-roasted, swapping sweet wheat buns for biscuits, and decreasing the acrylamide content of starch-based casseroles and rye bread by 50% would result in a 50% decrease in acrylamide exposure in adults. Among children, substituting boiled potatoes for chips and other friend potatoes and replacing biscuits with sweet wheat buns while lowering the acrylamide content of starch-based casseroles by 50% would lead to acrylamide exposure that is only half of the original exposure. In conclusions, dietary modifications could have a large impact in decreasing acrylamide exposure.

Intake of antioxidants and risk of type 2 diabetes in a cohort of male smokers.

BACKGROUND/OBJECTIVES: Oxidative stress may induce insulin resistance in peripheral tissues and impair insulin secretion from pancreatic ß-cells. Antioxidants are suggested to decrease the risk of diabetes through reduction of oxidative stress. However, only a few studies exist on dietary antioxidants and the risk of type 2 diabetes. We investigated the association of dietary antioxidants with incident type 2 diabetes in the α-Tocopherol, ß-Carotene Cancer Prevention Study cohort. SUBJECT/METHODS: The study cohort included 29,133 male smokers aged 50-69 years. During a median follow-up of 10.2 years 660 incident cases of diabetes were observed among the 25,505 men with a completed baseline food frequency questionnaire. RESULTS: Dietary α-tocopherol, ß-tocopherol and ß-tocotrienol were positively associated with the risk of diabetes when adjusted for age and supplementation (relative risk (RR) 1.17 (95% confidence interval (CI) 0.91-1.51) P for trend 0.02; RR 1.31 (95% CI 1.02-1.68) P for trend 0.01; RR 1.28 (95% CI 1.00-1.63) P for trend 0.01, respectively), but the association disappeared after multivariate adjustment (RR 0.92 (95% CI 0.71-1.19) P for trend 0.97; RR 1.06 (95% CI 0.82-1.36) P for trend 0.48; RR 1.04 (95% CI 0.80-1.35) P for trend 0.46, respectively). Other tocopherols and tocotrienols as well as vitamin C, carotenoids, flavonols and flavones had no association with risk of diabetes. CONCLUSIONS: Dietary antioxidants were not associated with a decreased risk of incident diabetes in middle-aged male smokers.

Dietary acrylamide intake and the risk of cancer among Finnish male smokers.

OBJECTIVE: To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. METHODS: The study consisted of 27,111 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. RESULTS: During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 ((95% confidence interval (CI) 1.01-1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. CONCLUSIONS: High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.

Insulin-like growth factors and liver cancer risk in male smokers.

BACKGROUND: The liver is the primary source of circulating insulin-like growth factor (IGF)-I, yet the relation between IGFs and liver cancer is uncertain. METHODS: In a case-cohort study within a cohort of 29,133 male smokers we examined associations of serum IGF-I and IGF binding protein (IGFBP)-3 with liver cancer (50 cases). RESULTS: Nonlinear associations between liver cancer and IGF-I and IGFBP-3 were observed (P=0.04 and P<0.01, respectively), strongest association at lowest levels (odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1-0.7 for 80 vs 30 ng ml(-1) of IGF-I; OR=0.2, 95% CI=0.1-0.6 for 1400 vs 700 ng ml(-1) of IGFBP-3). CONCLUSIONS: Low IGF-I and IGFBP-3 levels in male smokers are associated with increased risk of liver cancer.

Insulin-like growth factors and risk of kidney cancer in men.

BACKGROUND: Insulin-like growth factor-I (IGF-I) has been shown to increase kidney growth, glomerular filtration rate, and renal function. METHODS: In the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study of 29 133 Finnish male smokers aged 50-69 years, serum concentrations of IGF were measured in samples collected in 1985-1988. A total of 100 men with kidney cancer diagnosed > or =5 years after blood collection through 1997 were compared with a subcohort of 400 men; logistic regression models were used to estimate the risk of developing kidney cancer. RESULTS: Men with IGF-I levels >113 ng ml(-1) were 59% less likely to develop kidney cancer than men with levels < or =113 ng ml(-1) (odds ratio=0.41; 95% confidence interval=0.23-0.75). The IGF binding protein-3 (IGFBP-3) levels did not alter the association. No association was observed between IGFBP-3, or molar ratio of IGF-I/IGFBP-3, and kidney cancer. CONCLUSIONS: Low serum IGF-I levels in this cohort of older middle-aged male smokers are associated with increased kidney cancer risk, independent of IGFBP-3.

Predictors of vitamin D biochemical status in a large sample of middle-aged male smokers in Finland.

BACKGROUND/OBJECTIVES: As vitamin D deficiency is considered to be more common in regions with little solar ultraviolet (UV) light in winter, the aim of this study was to analyze predictors of vitamin D status by season within a large sample of male smokers from Finland, a country where there is negligible solar UV light in winter. SUBJECTS/METHODS: Vitamin D (measured by 25-hydroxyvitamin D (25(OH)D) nmol/l) and other serum constituents were assayed. Measured anthropometry, and self-reported dietary intake and physical activity (PA) were obtained and analyzed using stepwise multiple linear and logistic regression in 2271 middle-aged Finnish male smokers. RESULTS: In all, 27% of the population in winter and 17% in summer had serum 25(OH)D levels of <25 nmol/l, respectively. In summer, in multiple logistic regression analyses with adjustment for confounding and other predictors, high vitamin D intake (odds ratios (OR) 3.6; 95% confidence interval (CI) 1.5-8.5), some leisure time PA (OR 2.0; 95% CI 1.3-3.1) and having a body mass index (BMI) of >or=21 kg/m(2) compared with <21 kg/m(2) (OR 2.6; 95% CI 1.3-5.0), were associated with 25(OH)D >or=25 nmol/l. In winter, additional modifiable factors were occupational PA (OR 1.6; 95% CI 1.1-2.5) and high fish (OR 3.1; 95% CI 1.7-6.2) or poultry consumption (OR 1.7; 95% CI 1.2-2.5). Predictors from linear regression analyses of continuous levels of 25(OH)D were similar to the logistic regression analyses of 25(OH)D >or=25 nmol/l. CONCLUSION: In this Finnish sample more vitamin D intake, PA and having a BMI of >or=21 may have important modifiable roles in maintaining an adequate vitamin D status.

Dietary fiber and fiber-rich food intake in relation to risk of stroke in male smokers.

BACKGROUND/OBJECTIVES: There is convincing evidence that a high dietary fiber intake may lower the risk of coronary heart disease. However, the role of fiber in the prevention of stroke is unclear. We examined the associations of dietary fiber and fiber-rich food intake with risk of stroke within the Alpha-tocopherol, Beta-carotene Cancer Prevention Study. SUBJECTS/METHODS: Between 1985 and 1988, 26,556 Finnish male smokers aged 50-69 years, who had no history of stroke, completed a dietary questionnaire. During a mean follow-up of 13.6 years, 2702 cerebral infarctions, 383 intracerebral hemorrhages and 196 subarachnoid hemorrhages were ascertained. RESULTS: After adjustment for cardiovascular risk factors and folate and magnesium intakes, there was no significant association between intake of total fiber, water-soluble fiber, water-insoluble fiber, or fiber derived from fruit or cereal sources and risk of any stroke subtype. Vegetable fiber intake, as well as the consumption of fruit, vegetables and cereals, was inversely associated with the risk of cerebral infarction; the multivariate relative risks for the highest quintile of intake as compared with the lowest were 0.86 (95% confidence interval (CI): 0.76-0.99) for vegetable fiber, 0.82 (95% CI: 0.73-0.93) for fruit, 0.75 (95% CI: 0.66-0.85) for vegetables and 0.87 (95% CI: 0.74-1.03) for cereals. Vegetable consumption was inversely associated with risk of subarachnoid hemorrhage (relative risk for highest versus lowest quintile: 0.62; 95% CI: 0.40-0.98), and cereal consumption was inversely associated with risk of intracerebral hemorrhage (relative risk: 0.64; 95% CI: 0.41-1.01). CONCLUSIONS: These findings suggest a beneficial effect of the consumption of fruits, vegetables and cereals on stroke risk.

Effect of alpha-tocopherol and beta-carotene supplementation on the incidence of type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This study aimed to examine whether alpha-tocopherol or beta-carotene affected the occurrence of type 2 diabetes. METHODS: In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, controlled trial, 29,133 male smokers aged 50-69 years were randomised to receive either alpha-tocopherol (50 mg/day) or beta-carotene (20 mg/day) or both agents or placebo daily for 5-8 years (median 6.1 years). Baseline serum samples were analysed for alpha-tocopherol and beta-carotene using HPLC. Cases of diabetes were identified from a nationwide Finnish registry of patients receiving drug reimbursement for diabetes. Of 27,379 men without diabetes at baseline, 705 men were diagnosed with diabetes during the follow-up of up to 12.5 years. RESULTS: Baseline serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of diabetes in the placebo group: the relative risk (RR) between the highest and lowest quintiles of alpha-tocopherol was 1.59 (95% CI 0.89-2.84) and that for beta-carotene was 0.66 (95% CI 0.40-1.10). Neither supplementation significantly affected the incidence of diabetes: the RR was 0.92 (95% CI 0.79-1.07) for participants receiving alpha-tocopherol compared with non-recipients and 0.99 (95% CI 0.85-1.15) for participants receiving beta-carotene compared with non-recipients. CONCLUSIONS/INTERPRETATION: Neither alpha-tocopherol nor beta-carotene supplementation prevented type 2 diabetes in male smokers. Serum levels of alpha-tocopherol and beta-carotene were not associated with the risk of type 2 diabetes.

Physical activity and the risk of pneumonia in male smokers administered vitamin E and beta-carotene.

It has been proposed that moderate exercise may enhance the immune system. We evaluated whether physical activity at work or at leisure is associated with the risk of pneumonia, and whether the antioxidants vitamin E and beta-carotene affect pneumonia risk in physically active people. A cohort of 16 804 male smokers aged 50-69 years and working at study entry was drawn from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which examined the effect of vitamin E, 50 mg/day, and beta-carotene, 20 mg/day, on lung and other cancers. Physical activity at work, and the type of leisure-time exercise, were recorded at study entry. We retrieved the first occurrence of hospital-treated pneumonia during a 3-year follow-up from the National Hospital Discharge Register (133 cases). Physical activity at work and at leisure had no association with the risk of pneumonia. In participants with physically loading jobs, neither vitamin E nor beta-carotene affected the risk of pneumonia. In participants carrying out moderate or heavy exercise at leisure, beta-carotene had no effect, but vitamin E reduced the risk of pneumonia by 50% (95% CI: 16-70%). Previously, exercise has been shown to affect diverse laboratory measures of the immune system which are, however, only surrogate markers for the resistance to infections. The lack of association between physical activity and the risk of pneumonia observed in our study emphasizes the problem of drawing conclusions from surrogate end points. The finding that vitamin E reduced the risk of pneumonia in persons carrying out leisure-time exercise warrants further study.

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk.

An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR) = 0.8, 95% confidence interval (CI) = 0.5-1.1) nor for latent antibodies (RR = 0.6, 95% CI = 0.1-2.7). Similar risks were seen when analysis was restricted to case-control sets with at least 2 years lag before diagnosis (RR = 0.8, 95% CI = 0.5-1.2 and RR = 0.9, 95% CI = 0.1-4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM.

Polymorphisms in glutathione-S-transferase genes (GST-M1, GST-T1 and GST-P1) and susceptibility to prostate cancer among male smokers of the ATBC cancer prevention study.

Glutathione-S-transferase (GST) genes encode a family of detoxification enzymes that offer protection against endogenous and exogenous sources of reactive oxygen species (ROS). Germline variations in GST genes may alter the catalytic efficiency of GST isoenzymes leading to a potential increase in susceptibility to the genotoxic effects of ROS and electrophilic substances. A nested case-control study design was used to examine the association between the polymorphic GST genes and prostate cancer risk among Finnish male smokers of the ATBC Cancer Prevention Study. A case-case analysis was used to determine the association between these genetic polymorphisms and prostate cancer progression. Germline DNA was obtained from 206 prostate cancer cases and 194 controls frequency matched on age, intervention group and study clinic. Cases and controls were genotyped for three GST genes using MALDI-TOF mass spectrometry or multiplex polymerase chain reaction (PCR). Relative to the wild-type genotype, we observed a 36% reduction in prostate cancer risk associated with the GST-M1-null genotype (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.43, 0.95). Unlike GST-M1, GST-T1-null (OR 0.74, 95% CI 0.42, 1.33) and GST-P1*B (OR 1.10, 95% CI 0.72, 1.69) were not strongly associated with prostate cancer risk. We did not observe any significant associations between the selected polymorphic GST genes and tumour grade or stage. In conclusion, we did not observe a direct association between polymorphic GST-T1 or GST-P1 and prostate cancer risk. Our observation of a relatively strong inverse association between the GST-M1-null genotype and prostate cancer risk needs to be confirmed in larger association studies.