| 1. |
- Figlioli, G, et al.
(author)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Journal article (peer-reviewed)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 2. |
- Heath, A. K., et al.
(author)
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Nutrient-wide association study of 92 foods and nutrients and breast cancer risk
- 2020
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 22:1
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Journal article (peer-reviewed)abstract
- Background Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. Methods Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). Results Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. Conclusions Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
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| 3. |
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| 4. |
- Castro-González, A., et al.
(author)
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The K2-OjOS Project*New and revisited planets and candidates in K2 campaigns 5, 16, & 18
- 2022
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 509:1, s. 1075-1095
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Journal article (peer-reviewed)abstract
- We present the first results of K2-OjOS, a collaborative project between professional and amateur astronomers primarily aimed to detect, characterize, and validate new extrasolar planets. For this work, 10 amateur astronomers looked for planetary signals by visually inspecting the 20 427 light curves of K2 campaign 18 (C18). They found 42 planet candidates, of which 18 are new detections and 24 had been detected in the overlapping C5 by previous works. We used archival photometric and spectroscopic observations, as well as new high-spatial resolution images in order to carry out a complete analysis of the candidates found, including a homogeneous characterization of the host stars, transit modelling, search for transit timing variations and statistical validation. As a result, we report four new planets (K2-355 b, K2-356 b, K2-357 b, and K2-358 b) and 14 planet candidates. Besides, we refine the transit ephemeris of the previously published planets and candidates by modelling C5, C16 (when available) and C18 photometric data jointly, largely improving the period and mid-transit time precision. Regarding individual systems, we highlight the new planet K2-356 b and candidate EPIC 211537087.02 being near a 2:1 period commensurability, the detection of significant TTVs in the bright star K2-184 (V = 10.35), the location of K2-103 b inside the habitable zone according to optimistic models, the detection of a new single transit in the known system K2-274, and the disposition reassignment of K2-120 b, which we consider as a planet candidate as the origin of the signal cannot be ascertained.
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| 5. |
- Fanidi, Anouar, et al.
(author)
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Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56-0.88, Ptrend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39-0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42-0.87). Low 25(OH)D3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D3 had decreased risk of HNC, as well as improved survival following diagnosis.
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| 6. |
- Aglago, Elom K., et al.
(author)
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Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
- 2020
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In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666
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Journal article (peer-reviewed)abstract
- Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
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| 7. |
- Allen, Naomi E, et al.
(author)
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Selenium and Prostate Cancer : Analysis of Individual Participant Data From Fifteen Prospective Studies.
- 2016
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 108:11
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Journal article (peer-reviewed)abstract
- BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08).CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.
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| 8. |
- Almanza-Aguilera, Enrique, et al.
(author)
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Intake of the total, classes, and subclasses of (poly)phenols and risk of prostate cancer : a prospective analysis of the EPIC study
- 2023
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In: Cancers. - : MDPI. - 2072-6694. ; 15:16
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Journal article (peer-reviewed)abstract
- Existing epidemiological evidence regarding the potential role of (poly)phenol intake in prostate cancer (PCa) risk is scarce and, in the case of flavonoids, it has been suggested that their intake may increase PCa risk. We investigated the associations between the intake of the total and individual classes and subclasses of (poly)phenols and the risk of PCa, including clinically relevant subtypes. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort included 131,425 adult men from seven European countries. (Poly)phenol intake at baseline was assessed by combining validated center/country-specific dietary questionnaires and the Phenol-Explorer database. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). In total, 6939 incident PCa cases (including 3501 low-grade and 710 high-grade, 2446 localized and 1268 advanced, and 914 fatal Pca cases) were identified during a mean follow-up of 14 years. No associations were observed between the total intake of (poly)phenols and the risk of PCa, either overall (HRlog2 = 0.99, 95% CI 0.94–1.04) or according to PCa subtype. Null associations were also found between all classes (phenolic acids, flavonoids, lignans, and stilbenes) and subclasses of (poly)phenol intake and the risk of PCa, overall and according to PCa subtype. The results of the current large prospective cohort study do not support any association between (poly)phenol intake and PCa incidence.
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| 9. |
- Harms, Laura M., et al.
(author)
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Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations : a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2020
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In: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 123:2, s. 198-208
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Journal article (peer-reviewed)abstract
- Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0 center dot 66, 95 % CI 0 center dot 46, 0 center dot 96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0 center dot 58, 95 % CI 0 center dot 39, 0 center dot 86), 3,4-dihydroxyphenylpropionic acid (OR 0 center dot 63, 95 % CI 0 center dot 46, 0 center dot 87), ferulic acid (OR 0 center dot 65, 95 % CI 0 center dot 44, 0 center dot 96) and caffeic acid (OR 0 center dot 69, 95 % CI 0 center dot 51, 0 center dot 93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0 center dot 67, 95 % CI 0 center dot 48, 0 center dot 93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.
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| 10. |
- Jakszyn, Paula, et al.
(author)
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Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study
- 2020
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:4, s. 1027-1039
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Journal article (peer-reviewed)abstract
- Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04–1.27) for CRC, 1.24 (95% CI 1.09–1.41) for colon cancer and 0.99 (95% CI 0.83–1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31–2.01) for colon cancer overall and 2.11 (95% CI 1.50–2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.
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