Contenuto

COS Study

Objectives

This case-only study on breast cancer occurring before the age of 40, supported by the Commission of the European Communities¹, hopes to provide some answers to questions about the mechanisms of carcinogenesis and the perspective of preventing both genetic and sporadic breast cancers. The study is specifically investigating the interaction between genetic susceptibility and environmental factors, such as dietary factors, in the occurrence of breast cancer in women under the age of 40. The main gene-environment hypotheses that it is intended to test include the interaction with the consumption of various vegetables and fruit, dietary sources of phytoestrogens (soy products, other legumes, whole grain cereals and various seeds), dietary factors affecting insulin resistance (refined sugars, vegetable fibres, saturated and mono and polyunsaturated fats), and with overweight and abdominal obesity. Secondary aims under investigation include testing the interaction with oral contraceptives and radiation exposure in childhood, which have been hypothesised to increase the risk by a greater magnitude in mutation carriers than in non carriers.

Methodology

Heritable breast cancer represents 5-7% of all breast cancers and about half of these are related to specific gene mutation that confer very high risk of developing breast cancer (36-85%) and also ovarian cancer and male breast cancer at young ages. The C.O.S. study is collecting a few key information from several thousands European women who got breast cancer before the age of 40, an high proportion of whom are likely to be carriers (20%, according to our preliminary results). Over 2000 patients have already agreed to participate (in 9 centres of 7 European countries) and about 1500 have provided the required information and are being classified according to their probability of carrying a high penetrance mutation on the base of their family history of breast and ovarian cancer. The frequency of a given environmental exposure among breast cancer cases who most likely carry an high penetrance mutation (because of a highly predictive family history) is then compared with the frequency of the same exposure among breast cancer cases who most likely are not mutation carriers (because no other case occurred in an otherwise informative family). Whenever such frequencies come out significantly different, the study indicates a gene-environment interaction, i.e. that the factor under study affects the incidence of genetic cancer by a greater (or lesser) magnitude than the incidence of sporadic cancer. The aim is to recruit a sufficient number of cases among which to identify at least five hundred patients with an high probability of mutation (over 50% on average). These patients represent about 15% of the women analysed so far. The ultimate aim of the study, however, is to provide high risk families with evidence based recommendations for the primary prevention of hereditary breast cancer.

Preliminary results

So far results do not yet permit firm conclusions, but it appears that several risk factors widely recognised for sporadic breast cancer, such as early menarche, nulliparity, abdominal overweight, oral contraceptives, and frequent X-ray exposure in childhood, are associated with an higher risk of breast cancer in mutation carriers, while adolescent overweight is associated with lower risk.
The software developed for estimating the probability that a woman carries a mutation predisposing to breast cancer on the basis of her family history proved to be more accurate than other systems and has already been made available for research purposes to genetic counselling units. Researchers interested testing the software may contact the study coordinator.

Publications

Berrino F., Pasanisi P., Berrino J., Curtosi P., Bellati C.: A european case-only study on familial breast cancer. (pp 63-65). In: E. Riboli, R. Lambert (eds): "Nutrition and Lifestyle: Opportunities for Cancer Prevention". IARC Scientific Publications n. 156. Lyon: IARC, 2002
Pasanisi P., Berrino F., Bellati C., Sieri S., Krogh V.; Validity of the italian EPIC questionnaire to assess past diet. (pp 41-44). In: E. Riboli, R. Lambert (eds): "Nutrition and Lifestyle: Opportunities for Cancer Prevention". IARC Scientific Publications n. 156. Lyon: IARC, 2002
Berrino F., Bellati C.: COS, case only study on breast cancer before the age of 40. Announcement interaction in breast cancer. Epid. Prev. 23: 57-58, 1999.

¹ - This study is being carried out with the financial support of the Commission of the European Communities, specific RTD programme "Quality of Life and Management of Living Resources", Key Action 1 - Health Food and Environment, QLK1-2000-466-COS: "Case-Only Study on the interaction of diet and genetic predisposition in the occurrence of breast cancer in young women". It does not necessarily reflect its views and in no way anticipates the Commission's future policy in this area".

Last Update: March, 4^th 2008