Dataset Information

Plasma carotenoid- and retinol-weighted multi-SNP scores and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

ABSTRACT: BACKGROUND:Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in ?-carotene 15,15'-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. METHODS:We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. RESULTS:Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk [OR (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores = 1.04 (0.94-1.16) for ?-carotene, 1.08 (0.98-1.20) for ?-carotene, 1.04 (0.94-1.16) for ?-cryptoxanthin, 0.95 (0.87-1.05) for lutein/zeaxanthin, and 0.92 (0.83-1.02) for retinol]. Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. CONCLUSIONS:Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. IMPACT:Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer.

SUBMITTER: Hendrickson SJ

PROVIDER: S-EPMC3650115 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Plasma carotenoid- and retinol-weighted multi-SNP scores and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

Hendrickson Sara J SJ Lindström Sara S Eliassen A Heather AH Rosner Bernard A BA Chen Constance C Barrdahl Myrto M Brinton Louise L Buring Julie J Canzian Federico F Chanock Stephen S Clavel-Chapelon Françoise F Figueroa Jonine D JD Gapstur Susan M SM Garcia-Closas Montserrat M Gaudet Mia M MM Haiman Christopher A CA Hazra Aditi A Henderson Brian B Hoover Robert R Hüsing Anika A Johansson Mattias M Kaaks Rudolf R Khaw Kay-Tee KT Kolonel Laurence N LN Le Marchand Loic L Lissowska Jolanta J Lund Eiliv E McCullough Marjorie L ML Peplonska Beata B Riboli Elio E Sacerdote Carlotta C Sánchez María-José MJ Tjønneland Anne A Trichopoulos Dimitrios D van Gils Carla H CH Yeager Meredith M Kraft Peter P Hunter David J DJ Ziegler Regina G RG Willett Walter C WC

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130320 5

<h4>Background</h4>Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in β-carotene 15,15'-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined asso ...[more]

PMID: 23515144

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Project description:BackgroundScreening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM).ObjectiveTo examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.Design, setting, and participantsWe included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred.Outcome measurements and statistical analysisThe main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls.Results and limitationsAmong the cases, we found that 8 of the 47 SNPs were significantly associated (p<0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p<0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only.ConclusionsEight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa.Patient summaryIn this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.

Project description:ObjectiveCross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.DesignThis nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy.ResultsSoluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 4 vs 1=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk.ConclusionThis prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.

Dataset Information

Plasma carotenoid- and retinol-weighted multi-SNP scores and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

Publications

Plasma carotenoid- and retinol-weighted multi-SNP scores and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

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