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T J Key

Publications and source records attributed to T J Key.

At least 19 recordsLinked to original sources
PubMed2006

Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women.

OBJECTIVE: The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: The population are 2109 women who were control subjects in a case-control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch. RESULTS: Serum IGF-I levels were positively related to protein intake (P(trend)<0.001), but not related to energy, fat or carbohydrate intake. Positive relationships were observed with the intake of milk (P(trend)=0.007), calcium (P(trend)<0.001), magnesium (P(trend)=0.003), phosphorus (P(trend)<0.001), potassium (P(trend)=0.002), vitamin B6 (P(trend)=0.03), vitamin B2 (P(trend)=0.001) and inverse relationships with vegetables (P(trend)=0.02) and beta-carotene (P(trend)=0.02). IGFBP-3 was not related with most of the nutrients and foods in this study. CONCLUSIONS: In this population, circulating IGF-I is modestly related with the intake of protein and minerals, and with milk and cheese, while IGFBP-3 does not appear to be related with diet.

Adult↗
PubMed2006

Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.

Adult↗
PubMed2005

DNA repair polymorphisms and cancer risk in non-smokers in a cohort study.

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

Adult↗
PubMed2005

Long-term weight change and breast cancer risk: the European prospective investigation into cancer and nutrition (EPIC).

We examined prospectively the association between weight change during adulthood and breast cancer risk, using data on 1358 incident cases that developed during 5.8 years of follow-up among 40,429 premenopausal and 57,923 postmenopausal women from six European countries, taking part in the European prospective investigation into cancer and nutrition study. Multivariate Cox regression models were used to calculate hazard ratios according to weight change (kg), defined as the weight difference between age at enrollment and age 20 adjusted for other risk factors. Changes in weight were not associated with premenopausal breast cancer risk. In postmenopausal women, weight gain was positively associated with breast cancer risk only among noncurrent hormone replacement therapy (HRT) users (P-trend < or = 0.0002). Compared to women with a stable weight (+/-2 kg), the relative risk for women who gained 15-20 kg was 1.50 (95% confidence interval (CI) 1.06-2.13). The pooled RR per weight gain increment of 5 kg was 1.08 (95% CI 1.04-1.12). Weight gain was not associated with breast cancer risk in current HRT users, although, overall, these women experienced a much higher risk of breast cancer compared with nonusers. Our findings suggest that large adult weight gain was a significant predictor of breast cancer in postmenopausal women not taking exogenous hormones.

Adult↗
PubMed2005

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk.

The associations between serum concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP)-3 and risk of breast cancer were investigated in a nested case-control study involving 117 cases (70 premenopausal and 47 postmenopausal at blood collection) and 350 matched controls within a cohort of women from the island of Guernsey, UK. Women using exogenous hormones at the time of blood collection were excluded. Premenopausal women in the top vs bottom third of serum IGF-I concentration had a nonsignificantly increased risk for breast cancer after adjustment for IGFBP-3 (odds ratio (OR) 1.71; 95% confidence interval (CI): 0.74-3.95; test for linear trend, P=0.21). Serum IGFBP-3 was associated with a reduction in risk in premenopausal women after adjustment for IGF-I (top third vs the bottom third: OR 0.49; 95% CI: 0.21-1.12, P for trend=0.07). Neither IGF-I nor IGFBP-3 was associated with risk in postmenopausal women and serum IGF-II concentration was not associated with risk in pre- or postmenopausal women. These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer.

Adult↗
PubMed2005

Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

Alcohol Drinking↗
PubMed2005

Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition.

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids - notably androgens and oestrogens - promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Delta4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids -the androgens as well as the oestrogens - elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23-2.33), androstenedione 1.94 (1.40-2.69), testosterone 1.85 (1.33-2.57) and free testosterone 2.50 (1.76-3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42-3.02), oestradiol 2.28 (1.61-3.23) and free oestradiol (odds ratios 2.13 (1.52-2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

Aged↗
PubMed2004

A case--control study of selenium in nails and prostate cancer risk in British men.

In view of the experimental evidence suggesting that the micronutrient selenium reduces prostate cancer risk, we investigated the association between the selenium level in fingernails, a measure of long-term selenium intake, and prostate cancer risk in a case-control study among 656 British men, conducted in 1989-1992. Nail clippings were taken at the time of recruitment and selenium concentration, measured using neutron activation techniques, was successfully assayed for 300 case-control pairs and varied six-fold among the controls (0.59 p.p.m.; interquartile range, 0.50-0.71 p.p.m.). Nail selenium concentration was not significantly associated with prostate cancer risk: men in the highest quartile of nail selenium had a slightly increased risk compared with men in the lowest quartile (OR 1.24, 95 CI, 0.73-2.10); for advanced prostate cancer, men in the highest quartile had a slightly reduced risk compared with men in the lowest quartile (OR 0.78, 95% CI, 0.27-2.25). These results suggest that selenium is not strongly associated with prostate cancer risk in British men.

Aged↗
PubMed2003

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

Aged↗
PubMed2003

Diet and body mass index in 38000 EPIC-Oxford meat-eaters, fish-eaters, vegetarians and vegans.

OBJECTIVE: To compare body mass index (BMI) in four diet groups (meat-eaters, fish-eaters, vegetarians and vegans) in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford) and to investigate lifestyle and dietary factors associated with any observed differences. DESIGN: Cross-sectional analysis of self-reported dietary, anthropometric and lifestyle data. PARTICIPANTS: A total of 37875 healthy men and women aged 20-97 y participating in EPIC-Oxford. RESULTS: Age-adjusted mean BMI was significantly different between the four diet groups, being highest in the meat-eaters (24.41 kg/m(2) in men, 23.52 kg/m(2) in women) and lowest in the vegans (22.49 kg/m(2) in men, 21.98 kg/m(2) in women). Fish-eaters and vegetarians had similar, intermediate mean BMI. Differences in lifestyle factors including smoking, physical activity and education level accounted for less than 5% of the difference in mean age-adjusted BMI between meat-eaters and vegans, whereas differences in macronutrient intake accounted for about half of the difference. High protein (as percent energy) and low fibre intakes were the dietary factors most strongly and consistently associated with increasing BMI both between and within the diet groups. CONCLUSIONS: Fish-eaters, vegetarians and especially vegans had lower BMI than meat-eaters. Differences in macronutrient intakes accounted for about half the difference in mean BMI between vegans and meat-eaters. High protein and low fibre intakes were the factors most strongly associated with increasing BMI.

Adult↗
PubMed2003

Relation between body mass index and mortality in an unusually slim cohort.

STUDY OBJECTIVE: To investigate the relation between body mass index and mortality in an unusually slim cohort. DESIGN: Prospective cohort study. SETTING: United Kingdom. PARTICIPANTS: About 11,000 non-meat eaters and their meat eating friends and relatives, with a median age of 33 years were recruited between 1980 and 1984. More than 20% of the cohort had a self reported BMI below 20 kg/m(2) at recruitment. There were 195,000 person years of observation after a mean of 18.0 years of follow up. MAIN RESULTS: The characteristics of participants with a BMI below 18 kg/m(2) were favourable to a lower risk of cardiovascular disease. Nevertheless, these participants had an increased all cause death rate ratio (2.07, 95% CI 1.58 to 2.70) in comparison with participants who had a BMI between 20 and 22 kg/m(2). The death rate ratio for the slimmest category was also significantly increased for circulatory diseases (including ischaemic heart disease and cerebrovascular disease), respiratory diseases, and all other causes combined excluding all malignant neoplasms. This finding was consistent across a range of subgroups. CONCLUSIONS: Lean men and women (BMI <18 kg/m(2)) experience increased all cause mortality compared with those with a BMI between 20 and 22 kg/m(2). This pattern is not seen for cancer mortality, but is found for cardiovascular and respiratory diseases. It is important that public health messages regarding healthy eating are aimed at maintaining a healthy body weight rather than just "losing weight".

Adolescent↗
PubMed2002

A prospective study of serum bile acid concentrations and colorectal cancer risk in post-menopausal women on the island of Guernsey.

Secondary bile acids produced by the action of the colonic microflora may increase risk of colorectal cancer. Serum bile acid concentrations reflect the faecal bile acid profile and may be of value as biomarkers of risk of colorectal cancer. In a pilot investigation we examined: (i) the reproducibility of measurements of serum bile acids in two blood samples collected several years apart; and (ii) the hypothesis that relatively high levels of secondary bile acids, particularly deoxycholic acid, would be positively associated with an increased risk of colorectal cancer in a prospective study of 3680 women in Guernsey. There was poor reproducibility between repeat measurements of absolute serum concentrations of bile acids, but there was moderately good reproducibility for the ratios of serum concentrations of deoxycholic/cholic acid, lithocholic/chenodeoxycholic and secondary/primary bile acid concentrations (duplicate blood samples were available for 30 women). There were no significant differences in ratios of serum secondary to primary bile acids or in absolute concentrations of bile acids between the 46 women who developed colorectal cancer and their matched controls, although there was a suggestion that an increased risk was associated with a high ratio of deoxycholic/cholic acid (relative risk in top third compared to lower third=3.92 (95% CI 0.91-17.0, P for trend=0.096). These findings suggest that the ratios of serum bile acid concentrations are sufficiently reproducible for epidemiological studies, but that a larger study than our own is needed to adequately test the hypothesis of their relation to cancer risk.

Adult↗
PubMed2002

European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection.

The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

Adult↗