Final Report Summary - RISK FACTORS CANCER (Genetic and environmental risk factors for common malignant tumours especially breast cancer and melanoma.)
Using mainly population based research material both non genetic and genetic risk factors of common cancer types such as breast cancer and melanoma have been studied by help of the ERC advanced grant obtained 2011 (Risk factors of cancer).
The studies have both been undertaken regionally, nationally or in international collaborative groups. Using materials from population based case-control, cohort studies and very well defined patient materials from oncogenetic clinics a large number of questionnaires, pedigrees and tissue banks (tumour, normal tissue and blood) have been collected
For breast cancer and melanoma a large number of predisposing genes have been identified as well as the impact of already characterised high risk genes such as BRCA1 BRCA2 and CDKN2A has been studied.
Genes predisposing for either hormone receptor positive and negative breast cancer have been identified, as well as genes for families at the same time having breast cancer, ovarian cancer and prostate cancer. In breast cancer studies of non genetic risk factors mainly have addressed the role of reproductive and hormonal risk factors. Recently also dietary factors and physical activity have been investigated. The disease penetrance for mutation carriers of BRCA1/2 has been studied in a world wide material so far being the largest one. In non mutation carriers of BRCA1 and 2 new familal risk patterns have been described such as in patients with tubular cancer having a recessive familial disease pattern and patients with lobular breast cancer more often show a familial cancer pattern through the father and not the mother. Ovarian cancer often has been studied together with or by itself as this disease often is linked to breast cancer. Obesity, smoking and reproductive risk factors have been studied. In these studies beside BRCA1/2 a number of predisposing genes have been found. We have also identified risk factors and genes predisposing for male breast cancer.
In melanoma non genetic risk factors have included the role of UV-light exposure through the sun and through artificial sun beds, Also constitutional factors have been studied- Avoiding sun exposure is associated with a shorter survival than taking part in active sun bathing although the latter group has an increased risk for skin cancer.
Risk factor studies have also been undertaken in patients with soft tissue sarcoma and childhood cancer. The following risk factors we have characerized for sarcoma; family history, growth during puberty, tissue trauma, low parity and non use of oral contraceptives. Families with childhood cancer experience a higher risk for prostate and breast cancer and if multiple pediatric cancer cases occur in the same family more females are affected.
A number of challenges remain, Most of the risk genes for common cancers have been found and around 50-60% of the familial risk remains to through genes. Most of these genes are moderate or low risk genes and there is a general belief that they may interact with other genes and non genetic risk factors. Often the risk with a gene only is associated with a subgroup of the tumour disease and risk studies therefore need to be designed to evaluate the biology of the tumour. Tumour disease in individuals with strong risk genes such as BRCA1 and BRCA2 often is preventable by prophylactic surgery while presently it is unknown how disease in patients with moderate or low risk genes can be prevented although it is thought that modifying the environmental influence for these gene carriers may be very successful.
The studies have both been undertaken regionally, nationally or in international collaborative groups. Using materials from population based case-control, cohort studies and very well defined patient materials from oncogenetic clinics a large number of questionnaires, pedigrees and tissue banks (tumour, normal tissue and blood) have been collected
For breast cancer and melanoma a large number of predisposing genes have been identified as well as the impact of already characterised high risk genes such as BRCA1 BRCA2 and CDKN2A has been studied.
Genes predisposing for either hormone receptor positive and negative breast cancer have been identified, as well as genes for families at the same time having breast cancer, ovarian cancer and prostate cancer. In breast cancer studies of non genetic risk factors mainly have addressed the role of reproductive and hormonal risk factors. Recently also dietary factors and physical activity have been investigated. The disease penetrance for mutation carriers of BRCA1/2 has been studied in a world wide material so far being the largest one. In non mutation carriers of BRCA1 and 2 new familal risk patterns have been described such as in patients with tubular cancer having a recessive familial disease pattern and patients with lobular breast cancer more often show a familial cancer pattern through the father and not the mother. Ovarian cancer often has been studied together with or by itself as this disease often is linked to breast cancer. Obesity, smoking and reproductive risk factors have been studied. In these studies beside BRCA1/2 a number of predisposing genes have been found. We have also identified risk factors and genes predisposing for male breast cancer.
In melanoma non genetic risk factors have included the role of UV-light exposure through the sun and through artificial sun beds, Also constitutional factors have been studied- Avoiding sun exposure is associated with a shorter survival than taking part in active sun bathing although the latter group has an increased risk for skin cancer.
Risk factor studies have also been undertaken in patients with soft tissue sarcoma and childhood cancer. The following risk factors we have characerized for sarcoma; family history, growth during puberty, tissue trauma, low parity and non use of oral contraceptives. Families with childhood cancer experience a higher risk for prostate and breast cancer and if multiple pediatric cancer cases occur in the same family more females are affected.
A number of challenges remain, Most of the risk genes for common cancers have been found and around 50-60% of the familial risk remains to through genes. Most of these genes are moderate or low risk genes and there is a general belief that they may interact with other genes and non genetic risk factors. Often the risk with a gene only is associated with a subgroup of the tumour disease and risk studies therefore need to be designed to evaluate the biology of the tumour. Tumour disease in individuals with strong risk genes such as BRCA1 and BRCA2 often is preventable by prophylactic surgery while presently it is unknown how disease in patients with moderate or low risk genes can be prevented although it is thought that modifying the environmental influence for these gene carriers may be very successful.