Jennifer C. Melvin

Lipid Profiles and Risk of Breast and Ovarian Cancer in the Swedish AMORIS Study

Background: Obesity is a risk factor for breast and ovarian cancer; the mechanisms of action are not completely understood. Perturbed lipid metabolism often accompanies obesity; we therefore ascertained the associations between lipid components and breast and ovarian cancer risk in a prospective cohort study. Methods: A total of 234,494 women with baseline measurements of triglycerides and total cholesterol and glucose were selected from the AMORIS database.A total of 27,394 had measurements of high-density lipoprotein, low-density lipoprotein, apolipoprotein (Apo) B, and A-I. Associations between quartiles and dichotomized values of lipid components and breast and ovarian cancer risk were analyzed using Cox proportional hazard models. Results: We identified 6,105 women diagnosed with breast cancer and 808 women diagnosed with ovarian cancer. A weak trend was observed between triglycerides and breast cancer (HR, 1.01, 95% Confidence Interval, 0.94–1.09; 0.93 (0.86–1.00) 0.91 (0.84–0.99), second, third, and fourth quartiles; P = 0.01). No other associations between lipid components and risk of breast cancer or ovarian cancer showed statistical significance. Conclusions: A weak protective association was found between levels of triglycerides and risk of breast cancer. Impact: An analysis including information on tumour characteristics of ovarian cancer and breast cancer may provide more insight in possible links between lipid metabolism and the risk of these cancers. Cancer Epidemiol Biomarkers Prev; 21(8); 1381–4. ©2012 AACR.

Serum Lipid Profiles and Cancer Risk in the Context of Obesity: Four Meta-Analyses

The objective here was to summarize the evidence for, and quantify the link between, serum markers of lipid metabolism and risk of obesity-related cancers. PubMed and Embase were searched using predefined inclusion criteria to conduct meta-analyses on the association between serum levels of TG, TC, HDL, ApoA-I, and risk of 11 obesity-related cancers. Pooled relative risks (RRs) and 95% confidence intervals were estimated using random-effects analyses. 28 studies were included. Associations between abnormal lipid components and risk of obesity-related cancers when using clinical cutpoints (TC ≥ 6.50; TG ≥ 1.71; HDL ≤ 1.03; ApoA-I ≤ 1.05 mmol/L) were apparent in all models. RRs were 1.18 (95% CI: 1.08–1.29) for TC, 1.20 (1.07–1.35) for TG, 1.15 (1.01–1.32) for HDL, and 1.42 (1.17–1.74) for ApoA-I. High levels of TC and TG, as well as low levels of HDL and ApoA-I, were consistently associated with increased risk of obesity-related cancers. The modest RRs suggest serum lipids to be associated with the risk of cancer, but indicate it is likely that other markers of the metabolism and/or lifestyle factors may also be involved. Future intervention studies involving lifestyle modification would provide insight into the potential biological role of lipid metabolism in tumorigenesis.

Family history of breast cancer and its association with disease severity and mortality

A family history (FH) of breast cancer (BC) is known to increase an individuals risk of disease onset. However, its role in disease severity and mortality is less clear. We aimed to ascertain associations between FH of BC, severity and BC‐specific mortality in a hospital‐based cohort of 5354 women with prospective information on FH. We included women diagnosed at Guys and St Thomas’ NHS Foundation Trust between 1975 and 2012 (n = 5354). BC severity was defined and categorized as good, moderate, and poor prognosis. Data on BC‐specific mortality was obtained from the National Cancer Registry and medical records. Associations between FH and disease severity or BC‐specific mortality were evaluated using proportional odds models and Cox proportional hazard regression models, respectively. Available data allowed adjustment for potential confounders (e.g., treatment, socioeconomic status, and ethnicity). FH of any degree was not associated with disease severity at time of diagnosis (adjusted proportional OR: 1.00 [95% CI: 0.85 to 1.17]), which remained true also after stratification by period of diagnosis. FH of BC was not associated with BC‐mortality HR: 0.99 (95% CI: 0.93 to 1.05). We did not find evidence to support an association between FH of BC and severity and BC‐specific mortality. Our results indicate that clinical management should not differ between women with and without FH, when the underlying mutation is unknown.

Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I2 test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88–0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66–0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations.

Progression of breast cancer following locoregional ipsilateral recurrence: importance of interval time

Background:Studies comparing prognosis of breast cancer (BC) patients with and without locoregional recurrence (LR) present conflicting results. We aimed to improve our understanding of the impact of LR on prognosis by examining a large cohort of patients treated at Guy’s and St Thomas’ NHS Foundation Trust.Methods:Risk factors associated with BC-specific death were investigated using Cox proportional hazards regression in 5199 women diagnosed between 1975 and 2007. Breast cancer-specific death following LR was assessed with Poisson regression.Results:Overall, 552 women (11%) developed LR, with a median follow-up time of 4.28 years. Known factors associated with BC-specific death (tumour stage, grade, and nodal status) were of significance in our data. Women with a shorter disease-free interval had a worse prognosis. For instance, the HR for BC-specific death among women undergoing mastectomy with an LR 0.5–1 year after diagnosis of their primary tumour was 6.67 (95% CI: 3.71–11.99), when compared with women who did not experience LR.Conclusions:It often remains difficult to distinguish between a genuine LR and a new primary. The HRs for risk of BC-specific death following a second lesion suggest that they may act as a marker of systemic disease, large tumour burden, or depleted host defence. The clinically highly relevant impairment in prognosis calls for further research into the underlying mechanisms. We showed that for at least 15 years of follow-up, the prognosis in women following the occurrence of an LR may benefit from careful diagnostic and therapeutic management.

An investigation into the relationship between statins and cancer using population‐based data

An investigation into the relationship between statins and cancer using population-based data

Metabolic serum biomarkers for the prediction of cancer: a follow-up of the studies conducted in the Swedish AMORIS study

The Swedish Apolipoprotein MOrtality RISk study (AMORIS) contains information on more than 500 biomarkers collected from 397,443 men and 414,630 women from the greater Stockholm area during the period 1985–1996. Using a ten-digit personal identification code, this database has been linked to Swedish national registries, which provide data on socioeconomic status, vital status, cancer diagnosis, comorbidity, and emigration. Within AMORIS, 18 studies assessing risk of overall and site-specific cancers have been published, utilising a range of serum markers representing glucose and lipid metabolism, immune system, iron metabolism, liver metabolism, and bone metabolism. This review briefly summarises these findings in relation to more recently published studies and provides an overview of where we are today and the challenges of observational studies when studying cancer risk prediction. Overall, more recent observational studies supported previous findings obtained in AMORIS, although no new results have been reported for serum fructosamine and inorganic phosphate with respect to cancer risk. A drawback of using serum markers in predicting cancer risk is the potential fluctuations following other pathological conditions, resulting in non-specificity and imprecision of associations observed. Utilisation of multiple combination markers may provide more specificity, as well as give us repeated instead of single measurements. Associations with other diseases may also necessitate further analytical strategies addressing effects of serum markers on competing events in addition to cancer. Finally, delineating the role of serum metabolic markers may generate valuable information to complement emerging clinical studies on preventive effects of drugs and supplements targeting metabolic disorders against cancer.