A lifestyle intervention among elderly men on active surveillance for non-aggressive prostate cancer: a randomised feasibility study with whole-grain rye and exercise.

BACKGROUND: The prognosis for men with non-aggressive prostate cancer is good, and several studies have investigated the impact of lifestyle changes including physical activity and diet on the prognosis. Despite positive results in animal studies and a few human interventions with whole-grain rye on markers of prostate cancer progression, the feasibility of trials investigating such dietary changes in combination with physical activity remains largely unstudied. The primary aim was to investigate the feasibility of an intervention with high whole-grain rye intake and vigorous physical activity for 6 months in men diagnosed with prostate cancer. METHODS: In total, 26 men (53-72 years) recently diagnosed with non-aggressive prostate cancer and on active surveillance, were enrolled in 2011-2012 and randomly assigned to an intervention or a control group. The intervention included 170 g/day of whole-grain rye and 3 × 45 minutes/week of vigorous physical activity. The duration of the intervention was 6 months and end of follow-up 12 months after baseline. Clinic visits were scheduled at baseline and 3, 6 and 12 months after baseline. Compliance with the intervention was evaluated by diaries, food frequency questionnaires, biomarkers, and heart rate monitor data. The effect of the intervention was evaluated by linear multiple regression analysis. RESULTS: In the intervention group, the mean daily intake of whole-grain rye measured from diaries was 146 g (SD: 19) for the first 3 months and 125 g (SD: 40) for the last 3 months of the intervention. The median level (5th and 95th percentiles) of vigorous physical activity was 91 (17, 193) min/week for the first 3 months and 66 (13, 259) min/week for the last 3 months. No recordings of physical activity were done for the control group. Aerobic fitness (VO2 peak) increased in the intervention group compared to the control group after the intervention. No effects were found on other cardio-metabolic outcomes or prostate cancer progression. CONCLUSIONS: The lifestyle intervention appeared feasible for 6 months among Danish men and the results are encouraging for conducting full-scale studies, where the impact of whole-grain rye and vigorous physical activity on prostate cancer progression and metabolic parameters can be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01300104 . Registered on 18 February 2011.

The Impact of Husbands' Prostate Cancer Diagnosis and Participation in a Behavioral Lifestyle Intervention on Spouses' Lives and Relationships With Their Partners.

BACKGROUND: A prostate cancer diagnosis affects the patient and his spouse. Partners of cancer patients are often the first to respond to the demands related to their husband's illness and thus are likely to be the most supportive individuals available to the patients. It is therefore important to examine how spouses react and handle their husband's prostate cancer diagnosis. OBJECTIVE: The aim of this study was to explore how the prostate cancer diagnosis and the participation in their partners' behavioral lifestyle intervention program influenced the spouses' life, their relationship with their partner, and how they handle the situation. METHODS: Interviews were recorded with 8 spouses of potential low-risk prostate cancer patients on active surveillance as part of a clinical self-management lifestyle trial. RESULTS: We identified 3 phases that the spouses went through: feeling insecure about their situation, coping strategies to deal with these insecurities, and feeling reassured. CONCLUSIONS: The framework of a clinical trial should include mobilizing spousal empowerment so that they can take on an active and meaningful role in relation to their husband's disease. The observations here substantiate that the framework of active surveillance in combination with a lifestyle intervention in 1 specific prostate cancer clinical trial can mobilize spousal empowerment. IMPLICATIONS FOR PRACTICE: Creating well-designed clinical patient programs that actively involve the spouse appears to promote empowerment (meaning, self-efficacy, positive impact, and self-determination) in spouses. Spousal participation in clinical patient programs can give spouses relief from anxieties while recognizing them as a vital support for their husband.

Effects of smoking and antioxidant micronutrients on risk of colorectal cancer.

BACKGROUND & AIMS: Antioxidant intake has been reported to increase the risk of colorectal cancer (CRC) for smokers, yet reduce the risk for nonsmokers. We investigated the association between tobacco smoking and risk of colon or rectal cancer, and whether dietary and supplemental intake of the antioxidant vitamins A, C, E, ß-carotene, selenium, zinc, and manganese affects the risk of CRC among smokers. METHODS: Data on smoking habits and antioxidant intake were analyzed for 54,208 participants in the Danish Prospective Diet, Cancer and Health Study. Of these participants, 642 were diagnosed with colon cancer and 348 were diagnosed with rectal cancer. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard models. Principal components were used to analyze intake of combinations of antioxidants. RESULTS: Ever smoking increased the risk for CRC (hazard ratio, 1.19; 95% confidence interval, 1.03-1.37), especially for rectal cancer. Smoking for at least 20 years was associated with a 26% increase in risk of CRC, compared with never smokers, and smoking 20 g tobacco or more each day was associated with a 30% increase in risk. Smoking for more than 30 years, or more than 20 g tobacco each day, was associated with a 48% increase in risk of rectal cancer. We did not observe an interaction between smoking and antioxidant consumption on risk of CRC. CONCLUSIONS: Tobacco smoking increases the risk for CRC. We did not observe that consumption of antioxidant micronutrients modulates the effects of smoking on CRC risk.

Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain.

BACKGROUND: Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI. OBJECTIVE: The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI). DESIGN: The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis. RESULTS: HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed. CONCLUSION: TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.

GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer.

GPX1 encoding the enzyme glutathione peroxidase 1 (GPX1) and hOGG1 encoding the 8-oxoguanine glycosylase 1 (OGG1) may counteract oxidative stress and resulting DNA damage associated with lifestyle-related exposures. We examined whether the polymorphisms GPX1 Pro(198)Leu and OGG1 Ser(326)Cys or low erythrocyte GPX enzyme activity in pre-diagnostic blood samples are associated with colorectal cancer risk, and assessed possible interactions between the polymorphisms or enzyme activity and various lifestyle factors in relation to colorectal cancer risk. Additionally, we studied whether the GPX1 Pro(198)Leu polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective "Diet, Cancer and Health" study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993-1997. GPX1 Pro(198)Leu, hOGG1 Ser(326)Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among homozygous GPX1(198)Leu carriers, with incidence rate ratios for colorectal cancer of 1.45 (95% CI: 1.17-1.81, P=0.02) per 10g alcohol intake per day and 2.56 (95% CI: 0.99-6.61, P=0.02) among ever smokers compared with never smokers at enrolment. Erythrocyte GPX activity was influenced by the GPX1 Pro(198)Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence.

Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk.

Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element-binding protein), which is induced by glucose, and SREBP-1 (sterol response element-binding protein-1), which is stimulated by insulin through the PI3K/Akt signal transduction pathway. We investigated whether the genetic variability of the genes encoding for ChREBP, SREBP and FAS (respectively, MLXIPL, SREBF1 and FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases. Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by subgroups of age, menopausal status, hormone replacement therapy (HRT) use or BMI. On the other hand, we found that two SNPs in FASN were associated with BMI.

Social inequality and incidence of and survival from cancers of the oesophagus, stomach and pancreas in a population-based study in Denmark, 1994-2003.

We investigated the effect of socioeconomic, demographic and health-related indicators on the incidence of and survival from cancers of the oesophagus, stomach and pancreas diagnosed during 1994-2003 with follow-up through 2006 in Denmark using information from nationwide registers. The analyses were based on data on 2075 patients with cancer of the oesophagus, 2673 with stomach cancer and 3657 with pancreatic cancer in a cohort of 3.22 million persons born between 1925 and 1973 and aged >or=30 years. Overall, we found decreasing incidence rates of all three gastrointestinal cancers with increasing social advantage; this was most pronounced for oesophageal cancer and least for pancreatic cancer. The effect of socioeconomic position on survival after these cancers was less clear, perhaps due to the poor relative survival from these cancers and the fact that all three cancers are relatively rare in Denmark.

XPA A23G, XPC Lys939Gln, XPD Lys751Gln and XPD Asp312Asn polymorphisms, interactions with smoking, alcohol and dietary factors, and risk of colorectal cancer.

Polymorphisms in the XPD and the XPC gene have been associated with a lower DNA repair capacity. We determined the risk of colorectal cancer in association with the four polymorphisms XPA A23G, XPC Lys939Gln, XPD Lys751Gln and XPD Asp312Asn, and interactions between the polymorphisms and the environmental factors: smoking intensity, intake of alcohol, red meat, processed meat, fish and poultry, fruits and vegetables and dietary fibres, in relation to development of colorectal cancer in a study population of 405 colorectal cancer cases and a comparison group of 810 persons, nested within the Danish prospective cohort, Diet, Cancer and Health, of 57053 cohort members. No association was found between the XPC Lys939Gln, XPA A23G, XPD Lys751Gln, and XPD Asp312Asn polymorphisms and risk of colorectal cancer. The association of the XPD Lys751Gln polymorphism was statistically significantly different between genders, with a lower risk of colorectal cancer among women carrying the variant allele. We observed a statistically significant interaction between the XPC Lys939Gln polymorphism and consumption of red meat, with a 3.7-fold increase in colorectal cancer risk per 100g red meat intake per day among carriers of the homozygous variant, but virtually no effect of red meat intake among carriers of the wild type allele. In the light of the multiple comparisons being made, this result may be a chance finding. The results showed no interaction between the XPD Lys751Gln, XPA A23G, and XPD Asp312Asn polymorphisms and the environmental factors for the development of colorectal cancer. Overall, the results of the present study indicate that the four polymorphisms are not of major importance in colorectal cancer carcinogenesis.

Gene-environment interactions between smoking and a haplotype of RAI, ASE-1 and ERCC1 polymorphisms among women in relation to risk of lung cancer in a population-based study.

Homozygous carriers of a haplotype consisting of ERCC1 Asn118Asn(A), ASE-1 G-21A(G), RAI IVS1 A4364G(A) are at increased risk of lung cancer especially among women. Here, we analyse for gene-environment interactions with the predefined haplotype in a case cohort study including 428 lung cancer cases and a comparison group of 800 persons, all from the prospective Diet, Cancer and Health cohort of 57,000 Danes. At high smoking intensity (>20g tobacco/day), there was only additional risk of smoking intensity among women who were homozygous carriers of the haplotype (IRR=2.03; 95% CI: 1.10-3.73 per 5 additional g tobacco/day).