Journal Watch:
Highlights of recent work funded by the
WCRF International grant programme
Social and behavioural influences on children’s fruit and vegetable intake (WCRF Grant 2004/09)
Jones L R et al. Influences on child fruit and vegetable intake: sociodemographic, parental and child factors in a longitudinal cohort study. Public Health Nutrition, 2010; 13:1122-1130
Diets rich in fruit and vegetables during childhood have many benefits, which track through to adulthood. However, a large proportion of children in the UK do not meet the recommended intake. The Avon Longitudinal Study of Parents and Children (ALSPAC) study examined the sociodemographic, parental and personal factors that influence fruit and vegetable consumption in a cohort of 7285 children aged 7 living in the Southwest of England during 1999-2000.
The results showed that the average daily fruit and vegetable consumption (201g) was below the recommended amount for this age group (320g) and that intake was higher in girls than boys. Fruit and vegetable consumption was strongly related to maternal consumption and socio-economic status and whether the child was choosy about food. Children whose parents had rules about serving fruit and vegetables every day had a higher consumption. These findings will be useful in planning future campaigns to improve children’s eating habits.
Influences on adolescents sport participation (WCRF Grant 2007/47)
Prins P et al. Availability of sports facilities as moderator of the intention–sports participation relationship among adolescents. Health Education Research Advance Access published April 9, 2010
Participation in sporting activities declines rapidly during adolescence. It is important to identify the determinants of this in order to prevent the decline and plan physical activity promotion interventions. This study aimed to investigate environmental, such as availability of sport facilities, and individual influences on adolescents’ sport participation and how these factors interact.
Data on 247 adolescents, who participated in the ENvironmental Determinants of Obesity in Rotterdam SchoolchildrEn study, were included in this analysis. Individual determinants (such as sport participation, subjective norm, attitude and intention towards sport participation) were assessed trough questionnaires. Availability of sport facilities was assessed through a geographic information system.
Results show that attitude and subjective norm were associated with sports participation at follow-up. Although availability of sports facilities was not directly associated with sports participation, the intention–behaviour relationship was stronger when there were more facilities available. This suggests that when sufficient facilities are available, the intention to be active becomes important.
The implication of this study may be that motivating adolescents to participate in sports would be more effective when sufficient sport facilities are available. Further studies are needed to replicate the finding of this study and confirm this hypothesis.
Dietary protein in childhood as a factor in the timing of puberty (WCRF Grant 2006/39)
Günther A L B et al. Dietary Protein Intake throughout Childhood Is Associated with the Timing of Puberty. J Nutr. 2010;140(3):565-71
Early puberty onset is associated with hormone-related cancers in adulthood. This has generated interest in finding out what early-life exposures might affect the timing of puberty. Protein intake in childhood is seen as a potential factor, though previous studies have yielded conflicting results.
Using data from the longitudinal Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study, the researchers set out to examine if dietary protein intake at different stages of childhood can affect the onset of puberty. Both animal and vegetable protein intake was measured in a group of 112 children at 12 months, 18-24 months, 3-4 years and 5-6 years, using 3 day weighed dietary records. Height and weight measurements were taken, as well as age at menarche (girls) and voice beak (boys), to estimate the onset and the peak of puberty.
The study found that children with a higher animal protein intake at 5-6 years had an earlier onset of puberty by 0.6 years. Conversely, a higher intake of vegetable protein intake at 3-4 years and 5-6 years was associated with a delayed onset of puberty.
This study suggests that animal and vegetable protein intake in mid-childhood might differentially influence pubertal timing. Larger studies need to confirm these results as well as examine the difference between boys and girls and the ability to consider hormonal status.
Relationship between serum Vitamin B levels and lung cancer risk (WCRF Grant 2007/16)
Johansson M et al. Serum B vitamin levels and risk of lung cancer. Journal of the American Medical Association. 2010; 303: 2377
B-vitamins are essential for the manufacture of DNA and have been suspected of having a role in cancer. Compounds that interact closely with B-vitamins include methionine, an essential amino acid, and homocysteine. Thus, levels of these nutrients may also be implicated in cancer development.
This study investigated whether serum levels of four B-vitamins (B2, B6, folate and B12), methionine and homocysteine were associated with lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) - a large population cohort of more than 500,000 participants from 10 European countries. The researchers looked at 899 people who had donated blood and then later went on to develop lung cancer (11% were never smokers and 29% former smokers), as well as 1,770 people who had donated blood and did not develop the disease (39% never smokers and 37% former smokers).
The results suggest that above-average serum levels of both vitamin B6 and
methionine, measured on average 5 years prior to the onset of cancer, result in a reduction of at least 50 per cent in the risk of developing lung cancer. These results were independent of smoking status. A lower risk was also seen with higher levels of folate consumption.
The results show a potential link between serum B vitamin levels and the risk of lung cancer, but more research is needed to confirm that B-vitamins reduce lung cancer risk.
Body mass index as a prognostic marker for prostate cancer recurrence (WCRF Grant 2005/63)
Joep G H v Roermund et al. Body mass index as a prognostic marker for biochemical recurrence in Dutch men treated with radical prostatectomy. British Journal of Urology International. 2009; 104: 321-325
Studies on the relationship between obesity and prostate cancer have produced conflicting results. However, recent large studies found that obese men treated with radical prostatectomy (RP) had higher biochemical recurrence (BCR). Thus, it has been hypothesised that BMI could be used as a prognostic factor for recurrence.
To investigate this hypothesis, this study analysed the medical records of 1302 prostate cancer patients who had RP at two hospitals in the Netherlands. Preoperative eight and weight measures and clinical data were obtained retrospectively.
The results of this study showed that obese patients undergoing RP had no greater risk of developing BCR than normal-weight patients. The relatively few obese patients in this sample might explain the negative results. More research is needed to clarify whether body mass index can be used as a prognostic marker for prostate cancer recurrence.
Validation study of cytokine measurements in healthy subjects (WCRF Grant 2007/13)
Laure Dossus et al. Validity of multiplex-based assays for cytokine measurements in serum and plasma from “non-diseased” subjects: Comparison with ELISA. Journal of Immunological Methods, 2009; [Epub ahead of print]
Cytokine measurements in blood samples are used in large-scale epidemiological studies as a marker of low-grade chronic inflammation, which has been associated with a number of chronic diseases, including cancer. Multiplex-based immunoassays (MIA) allow the simultaneous measurement of multiple cytokines in small volumes of biological samples and enabling the characterisation of an individual’s cytokine profile in one measurement. However, the applicability of MIA to healthy individuals, as those participating in large cohort studies, has not been fully validated.
To explore the validity of this analytical method in untreated individuals, measurements of cytokines obtained by MIA were compared with those obtained by enzyme-linked immunosorbent assays (ELISA), which is considered the ‘gold standard’ method for cytokine analysis. However, more than one ELISA assay is needed to characterise an individual’s cytokine profile. Serum and plasma samples were taken from 36 healthy subjects participating in a large-scale epidemiological study.
The results of this study indicate that MIA can accurately estimate levels of cytokines that are present at relatively large concentrations (ng/mL) and can be used to estimate relative risk in large epidemiological studies. For cytokines present in smaller concentrations, ELISA is a more accurate method.
Caloric restriction and breast density (WCRF Grant 2005/35)
Gerco Haars et al. The influence of a period of caloric restriction due to the Dutch Famine on breast density. International Journal of Cancer. 2009; [Epub ahead of print]
In a recent cohort study of women exposed to the Dutch famine of 1944-1945, it was shown that short, intense caloric restriction at a young age increased breast cancer risk later in life and affected the levels of sex hormones and insulin growth factors (IGF). The IGF-system has been previously associated with breast density, a strong risk factor for breast cancer. Thus, breast density could be a possible intermediate between caloric restriction and breast cancer.
The aim of the current study was to evaluate how breast density is affected by short caloric restriction caused by the Dutch famine and whether age at exposure can modulate this effect. Breast density, assessed through mammograms, was measured in a sub-sample of 1035 women from the Dutch famine cohort. Subjects were divided into three groups, according to their level of severity of exposure to famine. Breast size and absolute and relative breast density were measured on a continuous scale.
The results showed no overall effect of exposure to famine on breast density. However, in accordance with the previous study, women severely exposed to famine before the age of 10 had a tendency to have higher absolute and relative dense tissue and smaller breast size. In conclusion this study does not support the role of breast density as the main intermediate in the relation between IGF and breast cancer.
Elevated blood glucose levels and risk of incident and fatal cancer (WCRF Grant 2007/09)
Tanja Stocks et al. Blood glucose and risk of incident fatal cancer in the Metabolic Syndrome and Cancer Project (Me-Can): Analysis of six prospective cohorts. 2009; [Epub ahead of print]
Prospective studies have shown that elevated blood glucose levels may be linked with an increased risk of cancer. However, the strength of this association has not been fully clarified among European populations.
The aim of this study was to investigate the association between blood glucose and risk of incident and fatal cancer in the Metabolic syndrome and Cancer project (Me-Can), a large study of six European cohorts. Data on glucose levels, including correction for random error, body mass index and smoking status were available for 274,126 men and 275,818 women. After an average follow-up of 10.4 years, 18,621 men and 11,664 women were diagnosed with cancer, and 6,973 men and 3,088 women died of cancer.
Results showed that elevated blood glucose, independent of body mass index (BMI) was significantly associated with increased risk of incident and fatal cancer at all sites combined. Positive associations were also found for several specific cancer sites, including liver, gallbladder and respiratory tract for men and pancreas, urinary bladder and cervix for women. The results were stronger in women than men and for fatal cancer compared to incident cancer. This study contributes to the evidence that high blood glucose may be a risk factor for cancer.
Early energy restriction and epigenetic changes in colorectal cancer risk (WCRF Grant 2007/54)
Laura A E Hughes et al. Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. Plos ONE. 2009; 4(11): e7951
Short-term energy restriction in early life may be linked to a lower risk of colorectal cancer. Some evidence suggests that cancer risk might be modulated through epigenetic changes. This study investigated the association between severe energy restriction in childhood and adolescence and epigenetic changes, characterised by CpG island methylator phenotype (CIMP), and subsequent colorectal cancer risk in the Netherlands Cohort Study (NLCS).
The NLCS included information on diet and risk factors for 120,856 individuals who grew up during the Dutch Hunger Winter (1944-45) and the less severe energy restriction periods of the World War II (1940-44). A sub-cohort of 4,631 individuals was followed-up for 7.3 years, during which time 603 colorectal incidence cases were recorded. Tumour tissue from cases was analysed for CIMP status. Place of residence and father’s employment status were used as a proxy of energy restriction for the 1940-45 and 1932-40 periods respectively.
The results of this study showed for the first time that severe energy restriction during adolescence and early adulthood is associated with epigenetic changes in colorectal cancer. These findings suggest that adolescence may be a critical period of development for epigenetic changes that influence CRC risk.
Coffee consumption and endometrial cancer risk (WCRF Grant 2004/16)
Emilie Friberg et al. Coffee drinking and risk of endometrial cancer – A population-based cohort study. International Journal of Cancer. 2009; 125: 2413–2417
Coffee consumption has been shown to improve insulin resistance, which has been directly associated with endometrial cancer risk. It has therefore been suggested that coffee consumption might reduce the risk of this disease, but so far only two prospective studies have tested this hypothesis.
Using data from the large Swedish Mammography Cohort, this study aimed to investigate the association between coffee intake and endometrial cancer prospectively. After 17.6 years of follow-up, 677 incident adenocarcinoma endometrial cancer cases were recorded among 60,634 women in the cohort. Self-reported coffee consumption was assessed at baseline and after 10 years. Information on weight, height, education, parity, medical history and lifestyle factors was also collected by questionnaire.
The results showed that the hypothesis that daily coffee consumption was associated with lower endometrial cancer risk, particularly among women with excess body weight (which is a risk factor for endometrial cancer). Each additional cup (200g) of coffee was associated with a risk reduction of 10 per cent overall, 12 per cent among overweight women and 20 per cent in obese women.
These findings could be of major public health significance if confirmed by further research. More studies are needed to investigate the biological mechanisms by which coffee reduces endometrial cancer risk.
IGF-I and infant body length and adiposity (WCRF Grant 2004/03)
Ken Ong et al. Insulin-like growth factor I concentrations in infancy predict differential gains in body length and adiposity: the Cambridge Baby Growth Study. American Journal of Clinical Nutrition. 2009; 90: 1-6
In recent studies in western settings formula milk-fed infants show greater gains in weight and length than breastfed infants and in later childhood these individuals have increased risks for obesity. It has been hypothesised that Insulin-like growth factor I (IGF-I) may influence gains in weight, length, BMI and adiposity in the first year of life.
This hypothesis was examined using a prospective longitudinal birth cohort of 1526 infants born between 2001 and 2006. Weight, length, and 4 skinfold thicknesses as an indicator of adiposity, were measured at ages 0, 3, and 12 months.
The results from this study suggest that in formula milk–fed infants, higher IGF-I concentrations may lead to faster gains in length. However, it is likely that other mechanisms explain the faster gains in weight, BMI, and adiposity in formula milk-fed infants.
Folate-pathway gene polymorphisms and prostate cancer (WCRF Grant 2007/07)
Simon Collin et al. Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis. Cancer Epidemiol Biomarkers Prevention. 2009; 18(9): 2528–39
Food fortification and the use of dietary supplements mean that it is very important to establish whether the folate metabolic pathway has a role in prostate cancer. Previous studies have shown inconclusive results between folate-pathway gene polymorphisms and prostate cancer.
The objective for this study was to investigate the effects of folate-pathway gene polymorphism and prostate cancer using three sets of data. A meta-analysis was conducted using data identified from three sources: 1) a systematic review, 2) unpublished data from four genome-wide association studies, and 3) a case-control study nested within the UK population–based Prostate Testing for Cancer and Treatment study (ProtecT).
The meta-analysis suggested that known common folate-pathway single nucleotide polymorphisms do not have significant effects on susceptibility to prostate cancer. Other approaches may therefore be needed to elucidate the possible role of food fortification and dietary supplements in the development of prostate cancer.
Life course sun exposure and prostate cancer risk (WCRF Grant 2006/15)
Rebecca Gilbert et al. Life course sun exposure and risk of prostate cancer: Population-based nested case-control study and meta-analysis. International Journal of Cancer. 2009; 125: 1414–1423
Previous ecological studies have reported an inverse association between sunlight levels and mortality from prostate cancer ,which could be related to an inverse association of vitamin D with prostate cancer.
In order to investigate the associations of life course exposure to sunlight with prostate cancer this study analysed data from a UK-wide nested case-control study and from a systematic review with meta-analysis.
The results from the ProtecT study and the meta-analysis provide little support for the hypothesis that increased exposure to sunlight may reduce prostate cancer risk. However, of particular interest was the finding from the meta-analysis that suggested that among men with prostate cancer, higher levels of sun exposure may increase the likelihood of developing advanced prostate cancer.
The results for advanced prostate cancer need to be replicated in future studies, as this has potential implications for both public health and vitamin D chemoprevention trials.
Vitamin D Receptor and Calcium Sensing Receptor polymorphisms and colorectal cancer risk (WCRF Grant 2005/12)
Mazda Jenab et al. Vitamin D Receptor and Calcium Sensing Receptor Polymorphisms and the Risk of Colorectal Cancer in European Populations . Cancer Epidemiology Biomarkers Prevention. 2009; 18(9): 2485-91
Increased levels of vitamin D and calcium may play a protective role in colorectal cancer (CRC) risk. A few studies have looked at whether polymorphisms of the vitamin D receptor (VDR) and the calcium sensing receptor (CASR) involved in the metabolism of calcium and vitamin D mediate these effects, but results have been null or inconsistent.
This case-control study, of 1248 cases and 1248 matched controls, was nested within the European Prospective Investigation in Cancer and Nutrition (EPIC). It assessed the association of VDR and CASR with CRC risk as well as the interactions with serum vitamin D concentrations and dietary calcium. It is particularly important as most previous studies used North American populations, and this is the first such study in Western European populations.
The results from this study showed an inverse association for the BB genotype of the VDR BsmI polymorphism and CRC risk, independent of serum 25OHD concentration and dietary calcium intake. The other polymorphisms assessed were not associated with colorectal cancer risk. Further studies with higher statistical power are needed to more clearly investigate any possible gene-diet-lifestyle interactions.
Cohort to study association between metabolic syndrome and cancer (WCRF Grant 2007/09)
Tanja Stocks et al. Cohort Profile: The Metabolic syndrome and Cancer project (Me-Can). International Journal of Epidemiology. 2009; [Epub ahead of print]
To date, little is known about the metabolic syndrome and cancer risk. In 2006, the Metabolic syndrome and Cancer project (Me-Can) was established (involving existing cohorts in Norway, Austria and Sweden) in order to provide a large pooled cohort to investigate factors of the metabolic syndrome on the association with cancer risk.
A total of 578,700 subjects, each with one baseline observation, will be used in Me-Can studies. The objective of the Me-Can project is to study the effect of key factors (such as body mass index and blood pressure), separately and combined, on the association with risk of cancer overall and of specific cancer sites among men and women. Both incident and fatal cancer endpoints are used. This highlights the importance of the Me-Can project given that recent studies have focused either on the association between the metabolic syndrome and risk of specific cancers, or between a single factor and cancer risk.
The main strengths of this cohort are the large data set from several population based-surveys as well as the use of high quality registers for follow-up. This results in an almost complete coverage of cancer cases in Norway and Sweden, and the cancer register in Austria has also shown a high coverage of diagnosed cancers.
Prostaglandin endoperoxidase synthase 2 and prostate cancer risk (WCRF Grant 2004/18)
A Murad et al. PTGS2–899G4C and prostate cancer risk: a population-based nested case–control study (ProtecT) and a systematic review with meta-analysis. Prostate Cancer and Prostatic Diseases. 2009; 1–5
Prostaglandin endoperoxidase synthase 2 (PTGS2) is a key regulator of inflammation and may play a role in prostate carcinogenesis. The polymorphism, –899G4C (rs20417), alters a transcription factor-binding site critical to COX-2 expression, which could affect inflammation and cancer risk.
This hypothesis was tested using a case–control study nested within the Prostate testing for cancer and Treatment (ProtecT) trial, including 1592 cases and 3028 controls with genotyping information. A meta-analysis of earlier published studies was also conducted.
This large study showed no evidence that rs20417 influences prostate cancer risk. The researchers suggest that future studies should focus on other SNPs relevant to the inflammatory pathway and that larger prostate cancer case–control series of advanced disease are initiated.
Childhood anthropometric measurements and adult cancer risk (WCRF Grant 2006/03)
Elise Whitley et al. Childhood stature and adult cancer risk: the Boyd Orr cohort. Cancer Causes and Control. 2009; 20(2): 243-251
Aspects of childhood diet may influence adult cancer risk. In this study researchers used anthropometric measurements such as foot length, shoulder breadth, height, leg length and trunk length (as indirect measures of childhood diet and nutritional status), to investigate the association between childhood diet and adult cancer risk using data from 2,642 members of the Boyd Orr cohort.
There was a suggestion of a possible small increase in cancer risk with increasing childhood stature, in particular with risk of breast and prostate cancers. The study found no evidence that any of the indicators of childhood growth used were more strongly associated with cancer risk than any other childhood anthropometric measures. This suggests that both genetic and environmental influences may play a role in final adult stature and future disease. It is therefore likely that a single measurement in childhood is not sufficient to explain all the inter-relationships involved.
Rapid weight gain in babies and childhood obesity (WCRF Grant 2004/03)
Ken K Ong et al. Infancy Weight Gain Predicts Childhood Body Fat and Age at Menarche in Girls. Journal of Clinical Endocrinology & Metabolism. 2009; 94(5): 1527-1532
Previous research has shown that rapid postnatal weight gain is associated with subsequent increased childhood adiposity, although the contribution of rapid weight gain during particular periods during infancy is unclear. This study aimed to determine which periods of weight gain in infancy are related to childhood adiposity and also to age at menarche in girls, using data from 2717 girls from a prospective UK birth cohort study. Body measurements were taken at the ages of two months, nine months and 19 months.
This study suggests that rapid weight gain during the first nine months of life is a risk factor for both increased childhood adiposity and early menarche in girls and that there was no such association with subsequent weight gain between nine and 19 months. The findings of this study indicate that interventions to avoid rapid weight gain in infancy could potentially reduce later adiposity and also avoid early menarche in girls.
Independent Mobility and Physical Activity in Children (WCRF Grant 2007/41)
Angie S Page et al. Independent mobility in relation to weekday and weekend physical activity in children aged 10-11 years: The PEACH project. The International Journal of Behavioural Nutrition and Physical Activity. 2009; 6(2)
Levels of independent mobility in children have decreased in recent years. This could explain, to some extent, reported reductions in physical activity in young people. This cross-sectional study by Page et al., investigated whether independent mobility in 1307 10-11 year old boys and girls from 23 schools in a large UK city was related to objectively measured physical activity.
This study reported that independent mobility appears to be an important correlate of weekday physical activity for both boys and girls. The research also found that boys had greater independent mobility and physical activity levels than girls. This study suggests that it is important to understand the factors that influence independent mobility in order to determine the optimum social and physical environment that encourages parents and adult carers to promote unsupervised physical activity.
Physical Activity and Postmenopausal Breast Cancer (WCRF Grant 2005/50)
Tricia M. Peters, et al. Physical activity and postmenopausal breast cancer risk in the NIH-AARP diet and health study. Cancer Epidemiology Biomarkers & Prevention. 2009; 18(1): 289-296.
Previous research has shown that physical activity is associated with reduced breast cancer risk but whether this association varies across breast cancer subtypes or is modified by reproductive and lifestyle factors is unclear. The study by Peters et al., examined physical activity in relation to postmenopausal breast cancer risk in a large prospective US study of 182,862 women and 6,609 cancer cases.
The study showed a positive association between physical activity and postmenopausal breast cancer, which was more pronounced in Estogen Receptor (ER)-negative tumours. This suggests that physical activity likely influences breast cancer risk via both estrogenic and estrogen-independent mechanisms.
Dietary Calcium, vitamin D intakes and Mammographic density in a British Birth Cohort (WCRF Grant 2005/11)
Guita Mishra et al. Dietary calcium and vitamin D intakes in childhood and throughout adulthood and mammographic density in a British birth cohort. British Journal of Cancer. 2008; 99: 1539-1543
Previous research has indicated that high intake of vitamin D and/or calcium may be associated with a decreased risk of breast cancer. A study co-funded by WCRF and Breast Cancer Campaign used a British birth cohort of 1161 women followed up since their birth in 1946, to examine the role of dietary calcium and vitamin D intakes in childhood, and throughout adulthood, in relation to mammographic density which is a strong risk factor for breast cancer.
The study found no evidence for long-term effects of calcium and vitamin D intakes on breast density at a mean age of 51 years. However, considering the biological plausibility of an association between calcium and vitamin D and breast cancer risk, these associations should be explored further in other cohort studies with repeat measurements of calcium and vitamin D intakes throughout life.
A school-based intervention to increase mothers’ fruit and vegetable intakes (WCRF Grant 2006/11)
Saskia J te Velde et al. Mothers’ involvement in a school-based fruit and vegetable promotion intervention is associated with increased fruit and vegetable intakes – The Pro Children study. International Journal of Behavioral Nutrition and Physical Activity. 2008; 5:48
School-based fruit and vegetable interventions can involve a family component, although the extent to which such activities impact on fruit and vegetable intake in parents is not currently well understood. This study analysed data from ‘the Pro Children Study’ a multi-component school based intervention from Spain, Norway and the Netherlands to evaluate the effects of this intervention on mothers’ intake levels as well as to assess associations between the level of involvement in the project and improvement in the mothers’ intake levels.
Results did not show an effect of the intervention on mothers’ fruit and vegetable intakes, mostly due to their low involvement in the project. This highlighted the need for more research to increase mothers’ involvement in school-based interventions.
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