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Timothy J Key

Publications and source records attributed to Timothy J Key.

At least 19 recordsLinked to original sources

Socioeconomic position and the risk of gastric and oesophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

OBJECTIVES: To evaluate the association of socioeconomic position with adenocarcinoma of the oesophagus and stomach. METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort comprises about 520 000 participants mostly aged 35-70 years. Information on diet and lifestyle was collected at recruitment. After an average follow-up of 6.5 years, 268 cases with adenocarcinoma of the stomach and 56 of the oesophagus were confirmed. We examined the effect of socioeconomic position on cancer risk by means of educational data and a computed Relative Index of Inequality (RII). In a nested case-control study, adjustment for Helicobacter pylori (H. pylori) infection was performed. RESULTS: Higher education was significantly associated with a reduced risk of gastric cancer [vs lowest level of education, hazard ratio (HR): 0.64, 95% Confidence intervals (CI): 0.43-0.98]. This effect was more pronounced for cancer of the cardia (HR: 0.42, 95% CI: 0.20-0.89) as compared to non-cardia gastric cancer (HR: 0.66, 95% CI: 0.36-1.22). Additionally, the inverse association of educational level and gastric cancer was stronger for cases with intestinal (extreme categories, HR: 0.13, 95% CI: 0.04-0.44) rather than diffuse histological subtype (extreme categories, HR: 0.71 95% CI: 0.37-1.40). In the nested case-control study, inverse but statistically non-significant associations were found after additional adjustment for H. pylori infection [highest vs lowest level of education: Odds ratio (OR) 0.53, 95% CI: 0.24-1.18]. Educational level was non-significantly, inversely associated with carcinoma of the oesophagus. CONCLUSION: A higher socioeconomic position was associated with a reduced risk of gastric adenocarcinoma, which was strongest for cardia cancer or intestinal histological subtype, suggesting different risk profiles according to educational level. These effects appear to be explained only partially by established risk factors.

Adenocarcinoma↗

Physical activity and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition Cohort.

Research conducted predominantly in male populations on physical activity and lung cancer has yielded inconsistent results. We examined this relationship among 416,277 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC). Detailed information on recent recreational, household and occupational physical activity, smoking habits and diet was assessed at baseline between 1992 and 2000. Relative risks (RR) were estimated using Cox regression. During 6.3 years of follow-up we identified 607 men and 476 women with incident lung cancer. We did not observe an inverse association between recent occupational, recreational or household physical activity and lung cancer risk in either males or females. However, we found some reduction in lung cancer risk associated with sports in males (adjusted RR = 0.71; 95% confidence interval 0.50-0.98; highest tertile vs. inactive group), cycling (RR = 0.73; 0.54-0.99) in females and non-occupational vigorous physical activity. For occupational physical activity, lung cancer risk was increased for unemployed men (adjusted RR = 1.57; 1.20-2.05) and men with standing occupations (RR = 1.35; 1.02-1.79) compared with sitting professions. There was no evidence of heterogeneity of physical activity associations across countries, or across any of the considered cofactors. For some histologic subtypes suggestive sex-specific reductions, limited by subgroup sizes, were observed, especially with vigorous physical activity. In total, our study shows no consistent protective associations of physical activity with lung cancer risk. It can be assumed that the elevated risks found for occupational physical activity are not produced mechanistically by physical activity itself but rather reflect exposure to occupation-related lung cancer risk factors.

Adult↗

Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC).

There is current interest in fish consumption and marine omega-3 (n-3) fatty acids and breast cancer risk. Some in vitro and animal studies have suggested an inhibitory effect of marine n-3 fatty acids on breast cancer growth, but the results from epidemiological studies that have examined the association between fish consumption and breast cancer risk in humans are inconsistent. We examined fish consumption and breast cancer risk in 310,671 women aged between 25 and 70 yr at recruitment into the European Prospective Investigation Into Cancer and Nutrition (EPIC). The participants completed a dietary questionnaire between 1992-98 and were followed up for incidence of breast cancer for a median of 6.4 yr. Hazard ratio for breast cancer by intake of total and lean and fatty fish were estimated, stratified by study centre and adjusted for established breast cancer risk factors. During follow-up, 4,776 invasive incident breast cancers were reported. No significant associations between intake of total fish and breast cancer risk were observed, hazard ratio (HR) 1.01 (95% confidence interval [CI] 0.99-1.02; p = 0.28 per 10 g fish/day). When examining lean and fatty fish separately, we found a positive significant association only in the highest quintile for fatty fish (HR 1.13, 95% CI 1.01-1.26), but test for trend was not significant (p = 0.10). No associations with breast cancer risk were observed when the study participants were subdivided by menopausal status. Although the period of follow-up is relatively short, the results provide no evidence for an association between fish intake and breast cancer risk.

Adult↗

TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: a prospective study.

In cancer patients, plasma often contains mutant DNA released by cancer cells. We have assessed the significance of plasma DNA mutations for subsequent cancer development in healthy subjects in a large longitudinal prospective study. The European Prospective Investigation into Cancer and Nutrition study was analyzed with a nested case-control design. Cases were nonsmokers or ex-smokers for >10 years and newly diagnosed with lung, bladder, or upper aerodigestive tract cancers or leukemia accrued after a median follow-up of 6.3 years. Controls were matched 2:1 for follow-up, age, sex, area of recruitment, and smoking status. KRAS2 mutations were detected by mutant-enriched PCR and sequencing (n = 1,098). TP53 mutations were detected by denaturing high-performance liquid chromatography, temporal temperature gradient electrophoresis, and sequencing (n = 550). KRAS2 or TP53 mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up. Among 137 subjects who developed bladder cancer, 5 had KRAS2 mutations [odds ratio (OR), 4.25; 95% confidence interval (95% CI), 1.27-14.15] and 7 had TP53 mutations (OR, 1.81; 95% CI, 0.66-4.97). There was a nonsignificant trend for association between TP53 mutations and bulky adducts in lymphocyte DNA (OR, 2.78; 95% CI, 0.64-12.17). This is the first report of TP53 or KRAS2 mutations in the plasma of healthy subjects in a prospective study, suggesting that KRAS2 mutation is detectable ahead of bladder cancer diagnosis. TP53 mutation may be associated with environmental exposures. These observations have implications for monitoring early steps of carcinogenesis.

Adult↗

Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

It is considered that fruit and vegetable (F&V) protect against oesophagus and gastric cancer (GC). However, 2 recent meta-analyses suggest that the strength of association on GC seems to be weaker for vegetables than for fruit and weaker in cohort than in case-control studies. No evidence exists from cohort studies about adenocarcinoma of oesophagus (ACO). In 521,457 men and women participating in the EPIC cohort in 10 European countries, information of diet and lifestyle was collected at baseline. After an average of 6.5 years of follow-up, a total of 330 GC and 65 ACO, confirmed and classified by a panel of pathologists, was used for the analysis. We examined the relation between F&V intake and GC and ACO. A calibration study in a sub-sample was used to control diet measurement errors. In a sub-sample of cases and a random sample of controls, antibodies against Helicobacter pylori (Hp) were measured and interactions with F&V were examined in a nested case-control study. We observed no association with total vegetable intake or specific groups of vegetables and GC risk, except for the intestinal type, where a negative association is possible regarding total vegetable (calibrated HR 0.66; 95% CI 0.35-1.22 per 100 g increase) and onion and garlic intake (calibrated HR 0.70; 95% CI 0.38-1.29 per 10 g increase). No evidence of association between fresh fruit intake and GC risk was observed. We found a negative but non significant association between citrus fruit intake and the cardia site (calibrated HR 0.77; 95% CI 0.47-1.22 per 100 g increase) while no association was observed with the non-cardia site. Regarding ACO, we found a non significant negative association for vegetable intake and for citrus intake (calibrated HRs 0.72; 95% CI 0.32-1.64 and 0.77; 95% CI 0.46-1.28 per 100 and 50 g increase, respectively). It seems that Hp infection does not modify the effect of F&V intake. Our study supports a possible protective role of vegetable intake in the intestinal type of GC and the ACO. Citrus fruit consumption may have a role in the protection against cardia GC and ACO.

Adenocarcinoma↗

Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study.

The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was < 1 microg on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk.

Adenocarcinoma↗

Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC).

BACKGROUND: Dietary factors are thought to have an important role in gastric and esophageal carcinogenesis, but evidence from cohort studies for such a role is lacking. We examined the risks of gastric cancer and esophageal adenocarcinoma associated with meat consumption within the European Prospective Investigation Into Cancer and Nutrition (EPIC) cohort. METHODS: A total of 521,457 men and women aged 35-70 years in 10 European countries participated in the EPIC cohort. Dietary and lifestyle information was collected at recruitment. Cox proportional hazard models were used to examine associations between meat intake and risks of cardia and gastric non-cardia cancers and esophageal adenocarcinoma. Data from a calibration substudy were used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. In a nested case-control study, we examined interactions between Helicobacter pylori infection status (i.e., plasma H. pylori antibodies) and meat intakes. All statistical tests were two-sided. RESULTS: During a mean follow-up of 6.5 years, 330 gastric adenocarcinoma and 65 esophageal adenocarcinomas were diagnosed. Gastric non-cardia cancer risk was statistically significantly associated with intakes of total meat (calibrated HR per 100-g/day increase = 3.52; 95% CI = 1.96 to 6.34), red meat (calibrated HR per 50-g/day increase = 1.73; 95% CI = 1.03 to 2.88), and processed meat (calibrated HR per 50-g/day increase = 2.45; 95% CI = 1.43 to 4.21). The association between the risk of gastric non-cardia cancer and total meat intake was especially large in H. pylori-infected subjects (odds ratio per 100-g/day increase = 5.32; 95% CI = 2.10 to 13.4). Intakes of total, red, or processed meat were not associated with the risk of gastric cardia cancer. A positive but non-statistically significant association was observed between esophageal adenocarcinoma cancer risk and total and processed meat intake in the calibrated model. In this study population, the absolute risk of development of gastric adenocarcinoma within 10 years for a study subject aged 60 years was 0.26% for the lowest quartile of total meat intake and 0.33% for the highest quartile of total meat intake. CONCLUSION: Total, red, and processed meat intakes were associated with an increased risk of gastric non-cardia cancer, especially in H. pylori antibody-positive subjects, but not with cardia gastric cancer.

Adenocarcinoma↗

Health effects of vegetarian and vegan diets.

Vegetarian diets do not contain meat, poultry or fish; vegan diets further exclude dairy products and eggs. Vegetarian and vegan diets can vary widely, but the empirical evidence largely relates to the nutritional content and health effects of the average diet of well-educated vegetarians living in Western countries, together with some information on vegetarians in non-Western countries. In general, vegetarian diets provide relatively large amounts of cereals, pulses, nuts, fruits and vegetables. In terms of nutrients, vegetarian diets are usually rich in carbohydrates, n-6 fatty acids, dietary fibre, carotenoids, folic acid, vitamin C, vitamin E and Mg, and relatively low in protein, saturated fat, long-chain n-3 fatty acids, retinol, vitamin B(12) and Zn; vegans may have particularly low intakes of vitamin B(12) and low intakes of Ca. Cross-sectional studies of vegetarians and vegans have shown that on average they have a relatively low BMI and a low plasma cholesterol concentration; recent studies have also shown higher plasma homocysteine concentrations than in non-vegetarians. Cohort studies of vegetarians have shown a moderate reduction in mortality from IHD but little difference in other major causes of death or all-cause mortality in comparison with health-conscious non-vegetarians from the same population. Studies of cancer have not shown clear differences in cancer rates between vegetarians and non-vegetarians. More data are needed, particularly on the health of vegans and on the possible impacts on health of low intakes of long-chain n-3 fatty acids and vitamin B(12). Overall, the data suggest that the health of Western vegetarians is good and similar to that of comparable non-vegetarians.

Diet, Vegetarian↗

The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women.

High levels of circulating insulin-like growth factor-I (IGF-I) and its major binding protein (IGFBP-3) at premenopausal ages have been associated with an increased breast cancer risk. We conducted a cross-sectional study (215 premenopausal women and 241 after natural menopause) nested within the Guernsey prospective studies to examine the relationship between the IGF system and mammographic features of the breast. The mammographically dense area in the breast increased with increasing serum levels of IGF-I (P for linear trend, P(t) = 0.05), IGF-II (P(t) = 0.08), and IGFBP-3 (P(t) = 0.01) only in premenopausal women. IGF-II and IGFBP-3 serum levels were associated with increases in the mammographically lucent area in both premenopausal (P(t) = 0.01 and 0.04, respectively) and postmenopausal women (P(t) < 0.001 for both), but these associations were no longer statistically significant after adjustment for body mass index and waist circumference. Neither the IGF-I/IGFBP-3 nor the IGF-II/IGFBP-3 molar ratio was associated with any of these mammographic features. The number of A alleles at a polymorphic locus in the promoter region of the IGFBP-3 gene was associated with increasing mean IGFBP-3 levels in both premenopausal (P(t) = 0.01) and postmenopausal (P(t) <0.001) women but not with mammographically dense area. These results support the hypothesis that the IGF system may affect the amount of mammographically dense tissue in premenopausal women, possibly by promoting cell proliferation and inhibiting apoptosis in the fibroglandular tissue. The findings also show strong relations between IGF-II and IGFBP-3 levels and the amount of mammographically lucent tissue, reflecting the associations between body adiposity and amount of fat tissue in the breast and between body adiposity and circulating levels of these growth factors.

Adult↗

Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition.

BACKGROUND: Current evidence suggests that high red meat intake is associated with increased colorectal cancer risk. High fish intake may be associated with a decreased risk, but the existing evidence is less convincing. METHODS: We prospectively followed 478 040 men and women from 10 European countries who were free of cancer at enrollment between 1992 and 1998. Information on diet and lifestyle was collected at baseline. After a mean follow-up of 4.8 years, 1329 incident colorectal cancers were documented. We examined the relationship between intakes of red and processed meat, poultry, and fish and colorectal cancer risk using a proportional hazards model adjusted for age, sex, energy (nonfat and fat sources), height, weight, work-related physical activity, smoking status, dietary fiber and folate, and alcohol consumption, stratified by center. A calibration substudy based on 36 994 subjects was used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. All statistical tests were two-sided. RESULTS: Colorectal cancer risk was positively associated with intake of red and processed meat (highest [>160 g/day] versus lowest [<20 g/day] intake, HR = 1.35, 95% CI = 0.96 to 1.88; Ptrend = .03) and inversely associated with intake of fish (>80 g/day versus <10 g/day, HR = 0.69, 95 % CI = 0.54 to 0.88; Ptrend<.001), but was not related to poultry intake. Correcting for measurement error strengthened the associations between colorectal cancer and red and processed meat intake (per 100-g increase HR = 1.25, 95% CI =1.09 to 1.41, Ptrend = .001 and HR = 1.55, 95% CI = 1.19 to 2.02, Ptrend = .001 before and after calibration, respectively) and for fish (per 100 g increase HR = 0.70, 95% CI = 0.57 to 0.87, Ptrend<.001 and HR = 0.46, 95% CI = 0.27 to 0.77, Ptrend = .003; before and after correction, respectively). In this study population, the absolute risk of development of colorectal cancer within 10 years for a study subject aged 50 years was 1.71% for the highest category of red and processed meat intake and 1.28% for the lowest category of intake and was 1.86% for subjects in the lowest category of fish intake and 1.28% for subjects in the highest category of fish intake. CONCLUSIONS: Our data confirm that colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake.

Adult↗

Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study.

OBJECTIVE: To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. DESIGN: Multicentre, prospective cohort study. SETTING: Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom). PARTICIPANTS: 74,607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables. MAIN OUTCOME MEASURES: Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression. RESULTS: An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%). CONCLUSION: The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.

Aged↗

Folate intake and colorectal cancer risk: a meta-analytical approach.

Adequate consumption of folate may reduce the risk of colorectal cancer. We performed a meta-analysis of 7 cohort and 9 case-control studies that examined the association between folate consumption and colorectal cancer risk. In cohort studies, the association between folate consumption and colorectal cancer risk was stronger for dietary folate (folate from foods alone; relative risk for high vs. low intake = 0.75; 95% CI = 0.64-0.89) than for total folate (folate from foods and supplements; relative risk for high vs. low intake = 0.95; 95% CI = 0.81-1.11) and there was no significant heterogeneity between studies. There was significant heterogeneity between case-control studies. These results offer some support for the hypothesis that folate has a small protective effect against colorectal cancer but confounding by other dietary factors cannot be ruled out.

Case-Control Studies↗

Consumption of vegetables and fruits and risk of breast cancer.

CONTEXT: The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption. OBJECTIVE: To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 285,526 women between the ages of 25 and 70 years, participating in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, recruited from 8 of the 10 participating European countries. Participants completed a dietary questionnaire in 1992-1998 and were followed up for incidence of cancer until 2002. MAIN OUTCOME MEASURES: Relative risks for breast cancer by total and specific vegetable and fruit intake. Analyses were stratified by age at recruitment and study center. Relative risks were adjusted for established breast cancer risk factors. RESULTS: During 1,486,402 person-years (median duration of follow-up, 5.4 years), 3659 invasive incident breast cancer cases were reported. No significant associations between vegetable or fruit intake and breast cancer risk were observed. Relative risks for the highest vs the lowest quintile were 0.98 (95% confidence interval [CI], 0.84-1.14) for total vegetables, 1.09 (95% CI , 0.94-1.25) for total fruit, and 1.05 (95% CI , 0.92-1.20) for fruit and vegetable juices. For 6 specific vegetable subgroups no associations with breast cancer risk were observed either. CONCLUSION: Although the period of follow-up is limited for now, the results suggest that total or specific vegetable and fruit intake is not associated with risk for breast cancer.

Adult↗

Reproducibility of a short semi-quantitative food group questionnaire and its performance in estimating nutrient intake compared with a 7-day diet diary in the Million Women Study.

OBJECTIVES: To assess the short- and long-term reproducibility of a short food group questionnaire, and to compare its performance for estimating nutrient intakes in comparison with a 7-day diet diary. DESIGN: Participants for the reproducibility study completed the food group questionnaire at two time points, up to 2 years apart. Participants for the performance study completed both the food group questionnaire and a 7-day diet diary a few months apart. Reproducibility was assessed by kappa statistics and percentage change between the two questionnaires; performance was assessed by kappa statistics, rank correlations and percentages of participants classified into the same and opposite thirds of intake. SETTING: A random sample of participants in the Million Women Study, a population-based prospective study in the UK. SUBJECTS: In total, 12 221 women aged 50-64 years. RESULTS: In the reproducibility study, 75% of the food group items showed at least moderate agreement for all four time-point comparisons. Items showing fair agreement or worse tended to be those where few respondents reported eating them more than once a week, those consumed in small amounts and those relating to types of fat consumed. Compared with the diet diary, the food group questionnaire showed consistently reasonable performance for the nutrients carbohydrate, saturated fat, cholesterol, total sugars, alcohol, fibre, calcium, riboflavin, folate and vitamin C. CONCLUSIONS: The short food group questionnaire used in this study has been shown to be reproducible over time and to perform reasonably well for the assessment of a number of dietary nutrients.

Cross-Sectional Studies↗

Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men.

BACKGROUND: Plasma concentrations of long-chain n-3 polyunsaturated fatty acids are lower in vegetarians and in vegans than in omnivores. No data are available on whether these concentrations differ between long- and short-term vegetarians and vegans. OBJECTIVES: We compared plasma fatty acid composition in meat-eaters, vegetarians, and vegans and examined whether the proportions of eicosapentaenoic acid (20:5n-3; EPA), docosapentaenoic acid (22:5n-3; DPA), and docosahexaenoic acid (22:6n-3; DHA) were related to the subjects' duration of adherence to their diets or to the proportions of plasma linoleic acid (18:2n-6; LA) and alpha-linolenic acid (18:3n-3; ALA). DESIGN: The present cross-sectional study included 196 meat-eating, 231 vegetarian, and 232 vegan men in the United Kingdom. Information on anthropometry, diet, and smoking habits was obtained through a questionnaire. Total fatty acid composition in plasma was measured. RESULTS: The proportions of plasma EPA and DHA were lower in the vegetarians and in the vegans than in the meat-eaters, whereas only small differences were seen for DPA. Plasma EPA, DPA, and DHA proportions were not significantly associated with the duration of time since the subjects became vegetarian or vegan, which ranged from <1 y to >20 y. In the vegetarians and the vegans, plasma DHA was inversely correlated with plasma LA. CONCLUSIONS: The proportions of plasma long-chain n-3 fatty acids were not significantly affected by the duration of adherence to a vegetarian or vegan diet. This finding suggests that when animal foods are wholly excluded from the diet, the endogenous production of EPA and DHA results in low but stable plasma concentrations of these fatty acids.

Adult↗

Genetic variation in the growth hormone synthesis pathway in relation to circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3, and breast cancer risk: results from the European prospective investigation into cancer and nutrition study.

Insulin-like growth factor-I (IGF-I) stimulates cell proliferation and can enhance the development of tumors in different organs. Epidemiologic studies have shown that an elevated level of circulating IGF-I is associated to increased risk of breast cancer as well as other cancers. Genetic variants affecting the release or biological action of growth hormone (GH), the main stimulator of IGF-I production, may predict circulating levels of IGF-I and have an effect on cancer risk. We tested this hypothesis with a large case-control study of 807 breast cancer patients and 1,588 matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 22 common single nucleotide polymorphisms in 10 genes involved in GH production and action (GHRH, GHRHR, SST, SSTR1-SSTR5, POU1F1, and GH1), and in parallel, we measured serum levels of IGF-I and IGFBP-3, its major binding protein, in samples of cases and controls. SST and SSTR2 polymorphisms showed weak but statistically significant associations with breast cancer risk. SSTR5 polymorphisms were associated with IGF-I levels, whereas one polymorphism in GHRHR and one in POU1F1 were associated with IGFBP-3 levels. Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk.

Adult↗

Is the association with fiber from foods in colorectal cancer confounded by folate intake?

The effect of multivariate adjustment including folate on the strong protective effect of fiber in foods on colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition was investigated in 1,721 cases identified in the latest follow-up. The inclusion of an additional 656 cases confirmed our previously published results, with a strong and significant reduction in colorectal cancer risk of approximately 9% for each uncalibrated quintile increase in fiber (P(linear trend) < 0.001) compared with an 8% reduction in our previous report, which had not been adjusted for folate. Inclusion of the other covariates (physical activity, alcohol, smoking, and red and processed meat) confirmed this significant inverse association for colon cancer and strengthened the association with left-sided colon cancer (P < 0.001). After maximum adjustment, the association between fiber and rectal cancer was not significant, as in our previous analysis. The association with fiber from different food sources was analyzed, but again, there were no significance trends after maximum adjustment.

Cohort Studies↗