Key findings

Key results and current scientific activity

Summary

  1. Successful follow-up of the 521,000 subjects enrolled in the EPIC cohort, with little loss to follow-up during this time period, and the identification of over 26,000 incident cases and nearly 16,000 deaths.


  2. Colon cancer etiology:
    1. The hypothesis that a diet high in fibre reduces colorectal cancer risk has been corroborated in the EPIC study. Our findings were published in parallel with the results from the PLCO cohort of the NIH-NCI. In that study, a similar protective effect of fibre on colorectal cancer polyps was observed. Together, these results indicate that fibre is protective both for the development of adenomatous polyps and for their malignant transformation.
    2. The hypotheses that consumption of red and processed meat increases colorectal cancer risk while intake of fish decreases risk is strongly supported by the EPIC results.
    3. The combination of these four dietary factors (i.e. fibre, fish, red and processed meats) plays a major role in colorectal cancer etiology in addition to alcohol intake, obesity and low physical activity.


  3. Breast cancer etiology:
    1. The role of endogenous steroid hormones in pre- and post-menopausal breast cancer has been investigated in EPIC in the largest studies conducted to date on this topic. We have shown that both estrogens and androgens increase breast cancer risk while SHBG decreases risk after menopause. In parallel, overweight and low physical activity increase breast cancer risk after menopause. On the contrary, before menopause, androgens increase breast cancer risk, progesterones decrease risk and SHBG and obesity are not associated with risk. These findings provide strong clues for further investigations of the metabolic and hormonal factors specifically related to pre- and post-menopausal breast cancer.
    2. We found that the consumption of fruit and vegetables is not associated with breast cancer risk. This is an important finding as it helps to narrow down the factors potentially involved in breast cancer etiology and prevention.


  4. Prostate cancer etiology:
    1. We have shown that similarly to breast cancer, prostate cancer risk is not related to fruit and vegetable consumption.


  5. Genetic factors:
    1. We have initiated a very large systematic investigation of the role of polymorphisms in genes involved in the metabolism of steroid hormones and growth factors that have a role in the etiology of breast and prostate cancers in combination with lifestyle and metabolic factors.

Incident tumours by major cancer sites for EPIC study population, 2004
Cancer Site

Number of Incident Cases

Men

Women

Colon-rectum

1910

810

1100

Breast

6218

-

6218

Prostate

1547

1547

-

Lung

1292

686

606

Endometrium

779

-

779

Ovary

620

-

620

Gastric (stomach + oesophagus)

541

338

203

Upper Gastrointestinal Tract (including oesophagus and larynx)

497

359

138

Kidney

366

196

170

Bladder

679

486

193

Cervix

649

-

649

Pancreas

374

174

200

Other

10619

2838

7781

Total

26091

8054

18037



Summary of Scientific Activity on Breast Cancer in the EPIC Study

Abstracts of the publications listed below can be accessed from the publications database (See Menu/Publications)
Topic Publications Main results
Fruits and vegetables JAMA 2005, van Gils CH et al No statistically significant decreased risks for fruits and vegetables
Body size Int J Cancer 2004, Lahmann PH et al Statistically significant increased risk for post-menopausal but not for pre-menopausal breast cancer. In post-menopausal breast cancer cases the effect is limited to women not using HRT
Adult weight gain Onland-MoretNC et al, submitted 2004 Statistically significant increased risk
Endogenous hormones, pre- menopause JNCI Kaaks R et al, in press 2004 Increased serum androgens clearly increase pre-menopausal breast cancer risk independent of body weight. Serum progesterone decreases risk.
Endogenous hormones, post- menopause Kaaks R et al, submitted 2004 Increased levels of serum estradiol and testosterone increase post-menopausal breast cancer risk while increased SHBG decrease risk
Hormone replacement therapy Int J Cancer 2004, Fournier A et al Synthetic progestins increase breast cancer risk but no increased risk for natural micronized progesterone (results from French EPIC cohort). Analyses on full EPIC cohort on-going
Phytoestrogens Cancer Epidemiol Biomarkers Prev 2004 Grace et al.; Am J Clin Nutr 2004 Keinan-Boker et al. One study found positive association with isoflavones in EPIC-Norfolk cohort and the other found no association with these phytoestrogens in EPIC-Utrecht cohort. Analyses with pooled data set are still on-going.


Summary of Scientific Activity on Colon Cancer in the EPIC Study

Abstracts of the publications listed below can be accessed from the publications database (See Menu/Publications)
Topic Publications Main results
Fibre Lancet 2003, Bingham S et al Inverse relation of dietary fibre with colorectal cancer incidence with the greatest protective effect in the left colon, and least in the rectum. No food source of fibre is significantly more protective than others.
Fibre2 Bingham S et al, submitted 2004 Confirmation of the above findings after adjustment for folate and with a longer follow-up.
Nuts Cancer Epidemiol Biomarkers Prev 2004, Jenab et al Higher nut and seed intake is not significantly associated to the risk of colorectal, colon, and rectal cancers in men but did show an inverse association with colon cancer in women.
Meat, fish, poultry Norat T et al, provisionally accepted 2004 High consumption of processed and/or red meat is associated with an increase in colorectal cancer risk, not explained by the substitution of fish by red meat and is less apparent in high fibre consumers. Fish consumption is significantly inversely associated with risk while there is no association with poultry.
Dairy foods RiboliE et al, Paper in preparation Intake of milk and cheese was significantly associated with reduced colorectal cancer risk. The data suggested an inverse association for yogurt. Dietary calcium and calcium from dairy products are also significantly inversely associated.
Hormone replace-ment therapy, oral contraceptives and reproductive factors Ongoing analysis Among postmenopausal women, ever use of hormone replacement therapy was significantly associated with a reduction in risk of colorectal cancer.
Current alcohol intake Ongoing analysis Preliminary results indicate that current alcohol intake is significantly positively associated with risk of rectal, but not of colon cancer.
Lifestyle, insulin, IGF-I Grant approved Nested case-control study (C-peptide, IGF-1 and IGFBP-1 and IGFBP-2, and HbA1c)
Inflammatory markers and adipo-cytokines & lifestyle Proposed study Nested case-control study (C- reactive protein, leptin, adiponectin, variants of the PPARγ and adiponectin gene)
Folate, 1 carbon methyl nutrients, gene variants and colon cancer Grant approved Nested case-control study (Folate, vitamins B, homocysteine, gene variants)


Summary of Scientific Activity on Prostate Cancer in the EPIC Study

Abstracts of the publications listed below can be accessed from the publications database (See Menu/Publications)
Topic Publications Main results or objectives
Rates and hypotheses IARC Sci Publ 156 2002, Key TJ. Threefold variation in rates across EPIC countries
Fruit and vegetables Int J Cancer 2004, Key T et al No association of fruit and vegetables with prostate cancer risk.
Foods and nutrients Ongoing analysis Preliminary results indicate that major foods and nutrients are not associated with overall prostate cancer risk; analyses for localized and advanced disease to follow
Serum sex hormones and IGF system Grant approved Nested case-control study (androgens, estrogens, IGF-I and IGF binding proteins)
Genetic polymorphisms for sex hormones and IGF system Ongoing analysis Nested case-control study (polymorphisms for hormone synthesis and catabolism genes, and hormone receptors)
Nutritional biomarkers Grant approved Nested case-control study (plasma fatty acids, carotenoids, tocopherols, vitamin D, folate, vitamin B12, homocysteine, selenium and phytoestrogens)
Biomarkers of infections Grant approved Nested case-control study (HPV 16 and 18, herpes simplex virus-2, gonorrhoea, chlamydia, syphilis)


Summary of Scientific Activity on Gastric Cancer in the EPIC Study

Abstracts of the publications listed below can be accessed from the publications database (See Menu/Publications)
Topics Publication Main results
Tobacco Int J Cancer 2003, Gonzalez CA et al Confirm that smoking is causally associated with GC risk in European population
Meat, nitrosamines and nitrites Ongoing analysis Preliminary results indicate that red and preserved meat increase GC risk
Fruit and vegetables intake Ongoing analysis Preliminary results indicate that fruit reduces GC risk and vegetable is not associated. Analyses will be redone with more cases and separately by histological type and cardia and non-cardia site
Body mass index and the risk Ongoing analysis Preliminary results indicate that BMI is associated with adenocarcinoma of oesophagus
Alcohol intake Ongoing analysis Preliminary results indicate that alcohol is not associated with gastric cancer risk
Diet diversity Ongoing analysis Preliminary results indicate that diet diversity is negatively associated with gastric cancer risk
Helicobacter pylori infection Ongoing analysis Preliminary results indicate that the OR associated with Hp is 3, being higher in Mediterranean countries but lower in Northern European countries
Tobacco smoking, Helicobacter pylori infection, polymorphism of metabolic genes Ongoing analysis Preliminary analysis show an interaction between smoking and some variants in metabolic genes
Helicobacter pylori infection, smoking, inflammatory responses genes Ongoing analysis Preliminary analysis show an interaction between Hp infection and some variants in inflammatorygenes
Prevalence of Helicobacter pylori infection and CagA positive strain in 10 European countries. Ongoing analysis Preliminary results indicate that the prevalence of Hp is higher in Mediterranean countries andlower in Northern European countries


Summary of Scientific Activity on Lung Cancer in the EPIC Study and GenAir

Ongoing Studies

Data on several analyses are mature for publication including meat, cholesterol, physical activity, smoking and occupational exposures. An assessment of the dose-response relation between lung cancer risk and tobacco smoking by means of biomarkers, such as cotinine in plasma and possibly carcinogenic components of tobacco that can be measured in blood, are planned. DNA adducts are being excluded because they require large amounts of DNA, but specific adducts could be measured in subgroups. Work on bio-mathematical cancer modelling on the induction of lung cancer by smoking is on-going with an assessment of the two-mutation-carcinogenesis model currently being done.


GenAir

GenAir is a case-control study nested within the EPIC cohort that has the primary aim to study the relation between air pollution or environmental tobacco smoke (ETS) and incident cancers of the bladder, lung, oral cavity, pharynx, larynx or leukaemia and mortality from respiratory diseases (COPD and emphysema).


Publications:

On plasma DNA: Gormally et al, Int J Cancer 2004
On ETS and lung cancer: Vineis P et al, submitted JAMA 2004
On DNA adducts and lung cancer: Peluso M et al, submitted Cancer Res 2004
On validation of laboratory measurements: Peluso M et al, submitted Mutat Res 2004


Summary of Scientific Activity on Endometrial Cancer in the EPIC Study

Several lifestyle factors, including excess weight, lack of physical activity, pre-existing diabetes, and use of exogenous estrogens unopposed by progestins, have been clearly implicated as possible causes of endometrial cancer. Nevertheless, further studies are needed to increase the understanding of the physiological mechanisms leading to this disease (Cancer Epidemiol Biomarkers Prev 2002, Kaaks et al). With over 800 cases of endometrial cancer (about 600 with pre-diagnostic blood samples), the EPIC study provides a unique resource for such studies, including investigations using biomarkers.


Current Ongoing Studies:

Preliminary analyses have confirmed the direct relation between excess weight and endometrial cancer risk. Studies on endogenous hormones have started focusing on the relations between risk with either pre- or postmenopausal blood levels of total and bioavailable androgens and estrogens, insulin, and IGF-binding proteins 1 and 2. In addition, studies are being initiated to examine the relationships of endometrial cancer with physical activity and anthropometry, and with lifetime history of smoking (suspected to be a protective factor among postmenopausal women). Studies on dietary patterns, glycemic index, and use of different types of postmenopausal hormone replacement therapy are ongoing and/or planned.



Summary of Scientific Activity on Ovarian Cancer in the EPIC Study

Ovarian cancer is the fourth most frequent cause of cancer death and the most lethal of all gynecological tumors in women from North America, Northern and Western Europe. Established risk factors for ovarian cancer are age, family history of ovarian cancer and infertility, while increasing parity, oral contraceptive (OC) use, hysterectomy or tubal ligation decrease risk. The protective effect of pregnancy has been uniformly demonstrated in North American, European and Asian populations, with a 10-16% decrease in risk for each additional pregnancy. In contrast, use of exogenous hormones for menopause-related symptoms, especially prolonged use of estrogens unopposed by progestins, could be associated with an increased risk of ovarian cancer incidence or mortality. While excess weight and pre-existing diabetes do not appear to be important risk factors, studies on physical activity have shown variable results, some studies showing a significant increase in risk among the more active women. Animal studies have led to some strong hypotheses about the role of endogenous hormones, particularly gonadotropins, but these have not been supported much by epidemiological studies in women (Cancer Epidemiol Biomarkers Prev, Lukanova & Kaaks, in press).


Current Ongoing Studies:

First analyses of ovarian cancer risk in relation to dietary intake patterns have begun (Nutr Cancer Schultz M, in press 2004) and a first article on fruit and vegetable consumption by Schulz et al. is in its final stages of preparation. Overall consumption of fruit and vegetables was unrelated to risk of ovarian cancer. There was evidence of a protective effect of a high intake of allium vegetables on cancer risk. Separate inspection of the fruit and vegetable-ovarian cancer association by histological subtype indicated some differential effects on ovarian cancer risk. Other analyses planned will focus on the relations between ovarian cancer risk and use of different types of HRT, excess body weight and physical activity, and menstrual and reproductive history.



Other cancer sites are the subject of on-going research, awaiting results.


Near future research activities

The key etiological research planned for the near future will be based on the baseline epidemiological and biological data of EPIC. Major areas of research will include the search for lifestyle, metabolic and genetic causes of cancers of the breast, colorectum, prostate, lung, endometrium, ovary, pancreas, bladder, stomach and upper gastro-intestinal tract. The following major etiological hypotheses will be investigated:

  1. The role of complex interactions between genetic, metabolic, hormonal and lifestyle factors, including diet, overweight, weight gain over lifetime, with particular focus on the "metabolic syndrome" hypothesis. This line of research seems of particular relevance for cancers of the breast, prostate, endometrium and kidney.
  2. The role of diet, as defined by a higher level of complexity that will include dietary patterns, glycaemic index, and some complex pathways such as the 1-carbon metabolism, the fatty acids-eicosonoids metabolism, and their role in inflammatory processes.
  3. The diversity and specificity of different combinations of risk factors in relation to specific subsites of cancers within a given cancer site and histology group. It is foreseeable that the new techniques for classifying tumours by patterns of somatic mutations will become readily available and applicable to the tumour samples that have been, and will be, collected within the EPIC study.
Special interest will continue to be devoted to some specific areas of work such as:
  1. Studies making use of biomarkers of diet and of exposure to exogenous carcinogens.
  2. Tobacco, particularly to the investigation of differences in lifestyle associated with quitting smoking, that can be of major interest for studying how to further prevent cancer in the growing number of middle-aged men and women who become ex-smokers.