AIM: We investigated the association between air pollution exposure and IBD.
METHODS: The European Prospective Investigation into Cancer and Nutrition cohort was used to identify cases with Crohn's disease (CD) (n = 38) and ulcerative colitis (UC) (n = 104) and controls (n = 568) from Denmark, France, the Netherlands, and the UK, matched for center, gender, age, and date of recruitment. Air pollution data were obtained from the European Study of Cohorts for Air Pollution Effects. Residential exposure was assessed with land-use regression models for particulate matter with diameters of <10 μm (PM10), <2.5 μm (PM2.5), and between 2.5 and 10 μm (PMcoarse), soot (PM2.5 absorbance), nitrogen oxides, and two traffic indicators. Conditional logistic regression analyses were performed to calculate odds ratios (ORs) with 95 % confidence intervals (CIs).
RESULTS: Although air pollution was not significantly associated with CD or UC separately, the associations were mostly similar. Individuals with IBD were less likely to have higher exposure levels of PM2.5 and PM10, with ORs of 0.24 (95 % CI 0.07-0.81) per 5 μg/m(3) and 0.25 (95 % CI 0.08-0.78) per 10 μg/m(3), respectively. There was an inverse but nonsignificant association for PMcoarse. A higher nearby traffic load was positively associated with IBD [OR 1.60 (95 % CI 1.04-2.46) per 4,000,000 motor vehicles × m per day]. Other air pollutants were positively but not significantly associated with IBD.
CONCLUSION: Exposure to air pollution was not found to be consistently associated with IBD.
METHODS: Within the prospective EPIC (European Prospective Investigation into Cancer) study, we set up a nested matched case-control study among 366,351 participants with inflammatory bowel disease data, including 256 incident cases of UC and 117 of CD, and 4 matched controls per case. Dietary intake was recorded at baseline from validated food frequency questionnaires. Incidence rate ratios of developing UC and CD were calculated for quintiles of the Mediterranean diet score and a posteriori dietary patterns produced by factor analysis.
RESULTS: No dietary pattern was associated with either UC or CD risks. However, when excluding cases occurring within the first 2 years after dietary assessment, there was a positive association between a "high sugar and soft drinks" pattern and UC risk (incidence rate ratios for the fifth versus first quintile, 1.68 [1.00-2.82]; Ptrend = 0.02). When considering the foods most associated with the pattern, high consumers of sugar and soft drinks were at higher UC risk only if they had low vegetables intakes.
CONCLUSIONS: A diet imbalance with high consumption of sugar and soft drinks and low consumption of vegetables was associated with UC risk. Further studies are needed to investigate whether microbiota alterations or other mechanisms mediate this association.
METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years.
RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p
METHODS: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.
RESULTS: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10(-4); OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P = 1.86 × 10(-4); OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r(2) ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.
CONCLUSION: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.
IMPACT: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.
METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia.
RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75).
CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.
METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.
RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P s) for the association observed between variants at 12p11 and breast cancer risk.