| 1. |
- Zhang, Xuehong, et al.
(författare)
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Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status : a pooled analysis of 18 prospective cohort studies
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : OXFORD UNIV PRESS. - 0002-9165 .- 1938-3207. ; 95:3, s. 713-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. Objective: We investigated these associations in a pooled analysis of 18 cohort studies. Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. Results: alpha-Carotene, beta-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): alpha-carotene (0.87; 95% CI: 0.78, 0.97), beta-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): a-carotene (1.04; 95% CI: 0.99, 1.09), beta-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for beta-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend <= 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Conclusions: Intakes of alpha-carotene, beta-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources. Am J Clin Nutr 2012;95:713-25.
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| 2. |
- Jung, Seungyoun, et al.
(författare)
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Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status
- 2013
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP): Policy B1. - 0027-8874 .- 1460-2105. ; 105:3, s. 219-236
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptornegative (ER) breast cancer has few known or modifiable risk factors. Because ER tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER breast cancer. less thanbrgreater than less thanbrgreater thanAmong 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER) and 4821 ER breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided. less thanbrgreater than less thanbrgreater thanTotal fruit and vegetable intake was statistically significantly inversely associated with risk of ER breast cancer but not with risk of breast cancer overall or of ER tumors. The inverse association for ER tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI 0.74 to 0.90) for ER breast cancer and 1.04 (95% CI 0.97 to 1.11) for ER breast cancer (Pcommon-effects by ER status andlt; .001). Total fruit consumption was non-statistically significantly associated with risk of ER breast cancer (pooled multivariable RR comparing the highest vs lowest quintile 0.94, 95% CI 0.85 to 1.04). less thanbrgreater than less thanbrgreater thanWe observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER breast cancer in our large pooled analyses.
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| 3. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 4. |
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| 5. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 6. |
- Barrdahl, Myrto, et al.
(författare)
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A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer : Results from the Breast and Prostate Cancer Cohort Consortium
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:6, s. 1182-1188
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom=3.05, 95%CI=1.72-5.44, Phom=1.47 × 10-4), MAST2-rs12124649 (ORhom=1.73, 95% CI =1.18-2.54, Phom=5.24 × 10-3), and INSR-rs10500204 (ORhom=1.96, 95% CI=1.44-2.67, Phom=1.68 × 10-5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom=1.78, 95% CI=1.30-2.44, Phom=3.23 × 10-4). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
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| 7. |
- Barrdahl, Myrto, et al.
(författare)
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Association of breast cancer risk loci with breast cancer survival
- 2015
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 137:12, s. 2837-2845
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Tidskriftsartikel (refereegranskat)abstract
- The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; ptrend=2.84 x 10-4; HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p2DF=1.45 x 10-3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend=6.6 x 10-4; HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p2DF=1.25 x 10-4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.
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| 8. |
- Campbell, Peter T, et al.
(författare)
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Body Size Indicators and Risk of Gallbladder Cancer : Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies.
- 2017
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 26:4, s. 597-606
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking.Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI).Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m2, HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m2, HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors.Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks.Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR.
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| 9. |
- Fortner, Renée T., et al.
(författare)
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Ovarian cancer risk factors by tumor aggressiveness : An analysis from the Ovarian Cancer Cohort Consortium
- 2019
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:1, s. 58-69
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
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| 10. |
- Fuhrman, Barbara J, et al.
(författare)
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Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts
- 2021
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Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:8, s. 2246-2255
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Tidskriftsartikel (refereegranskat)abstract
- The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. SIGNIFICANCE: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.
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