Essential fats for future health. Proceedings of the 9th Unilever Nutrition Symposium, 26-27 May 2010

The 9th Unilever Nutrition Symposium entitled 'Essential fats for future health', held on 26-27 May 2010, aimed to review the dietary recommendations for essential fatty acids (EFA); discuss the scientific evidence for the roles of EFA in cognition, immune function and cardiovascular health; and to identify opportunities for joint efforts by industry, academia, governmental and non-governmental organizations to effectively improve health behaviour. This paper summarizes the main conclusions of the presentations given at the symposium. Linoleic acid (LA) and α-linolenic acid (ALA) are EFA that cannot by synthesized by the human body. Docosahexaenoic acid (DHA) is considered as conditionally essential because of its limited formation from ALA in the human body and its critical role in early normal retinal and brain development and, jointly with eicosapentaenoic acid (EPA), in prevention of cardiovascular disease (CVD). Some evidence for possible beneficial roles of n-3 fatty acids for immune function and adult cognitive function is emerging. A higher consumption of polyunsaturated fatty acids (PUFA; >10%E), including LA, ALA and at least 250-500 mg per day of EPA+DHA, is recommended for prevention of coronary heart disease (CHD). Two dietary interventions suggest that EFA may affect CVD risk factors in children similarly as in adults. To ensure an adequate EFA intake of the population, including children, public health authorities should develop clear messages based on current science; ensure availability of healthy, palatable foods; and collaborate with scientists, the food industry, schools, hospitals, health-care providers and communities to encourage consumers to make healthy choices.     

Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years

Objective

Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients ≤ 70 years.

Methods

Consecutive EC patients ≤ 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS).

Results

Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified.

Conclusions

Molecular screening for LS in patients with EC diagnosed ≤ 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age.     

A combined analysis of genome-wide association studies in breast cancer

In an attempt to identify common disease susceptibility alleles for breast cancer, we performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. Tests for association were performed for 285,984 SNPs. Evidence for association with SNPs in genes in specific pathways was assessed using a permutation-based approach. We confirmed associations with loci reported by previous GWAS on 1p11.2, 2q35, 3p, 5p12, 8q24, 10q23.13, 14q24.1 and 16q. Six SNPs with the strongest signals of association with breast cancer, and which have not been reported previously, were typed in two further studies; however, none of the associations could be confirmed. Suggestive evidence for an excess of associations was found for genes involved in the regulation of actin cytoskeleton, glycan degradation, alpha-linolenic acid metabolism, circadian rhythm, hematopoietic cell lineage and drug metabolism. Androgen and oestrogen metabolism, a pathway previously found to be associated with the development of postmenopausal breast cancer, was marginally significant (P = 0.051 [unadjusted]). These results suggest that further analysis of SNPs in these pathways may identify associations that would be difficult to detect through agnostic single SNP analyses. More effort focused in these aspects of oncology can potentially open up promising avenues for the understanding of breast cancer and its prevention.     

Attitude towards pre-implantation genetic diagnosis for hereditary cancer

The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition. Forty-eight Von Hippel-Lindau and 18 Li–Fraumeni Syndrome families were identified via the 9 family cancer clinics in the Netherlands. In total, 216 high risk family members and partners were approached, of whom 179 (83%) completed a self-report questionnaire. Of the high risk family members, 35% expressed a positive attitude towards PGD. Those with a current desire to have children were significantly more likely to have a positive attitude: 48% would consider the use of PGD. No other sociodemographic, medical or psychosocial variables were associated significantly with a positive attitude. The most frequently reported advantage of PGD is the avoidance of a possible pregnancy termination. Uncertainty about late effects was the most frequently reported disadvantage. These results indicate that approximately half of those contemplating a future pregnancy would consider the use of PGD. The actual uptake, however, is expected to be lower. There is no indication that psychosocial factors affect interest in PGD.     

Referral rates and trends in radiotherapy as part of primary treatment of cancer in South Netherlands, 1988-2002.

BACKGROUND AND PURPOSE: To study referral rates and time trends in the use of primary radiotherapy (RT). PATIENTS AND METHODS: The proportion and number of irradiated patients were calculated in a population-based setting among 58,436 cancer patients diagnosed between 1988 and 2002. RESULTS: The number of patients receiving RT within 6 months of diagnosis (RT6mo) increased by about 3.3% annually, the proportion of all incident cases that received RT6mo remained stable (+/-30%). Only 20% of elderly patients (75+) received RT6mo. The proportion of cancer patients that received RT6mo increased markedly between 1988-1992 and 1998-2002 for patients with prostate cancer (15 and 28%, respectively), rectal cancer (33 and 43%) and brain tumours (48 and 67%). The absolute number of irradiated breast cancer patients increased 30% between 1988 and 2002. Among patients with rectal cancer, a shift occurred from postoperative to preoperative RT since 1995. The percentage of irradiated patients with stage I endometrial cancer decreased from 47% in 1988-1992 to 15% in 1998-2002. CONCLUSIONS: The percentage of cancer patients who received primary RT remained stable throughout 1988-2002, being consistently lower for older patients. The increased number of irradiated patients was due mainly to earlier detection and the ageing of the population. To clarify the overall percentage of patients irradiated, population-based studies on RT given after 6 months since diagnosis are warranted.