Background

Lead (Pb) is classified as a probable human carcinogen. However, its role in renal cell cancer (RCC) has not been established. Calcium and vitamin D may off-set toxicity in vivo.

Methods

In this nested case-control study, whole blood lead (Pb), total serum calcium, and serum 25-hydroxyvitamin D were measured in blood drawn prior to diagnosis among male smokers participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Single nucleotide polymorphisms (SNPs) in five genes (CALB1, TRPV5, TRPV6, VDR, and ALAD) related to lead toxicity or calcium transport were genotyped. Logistic and linear regression were used to determine RCC risk and time to diagnosis (respectively), adjusting for other risk factors.

Results

Among 154 newly diagnosed cases and 308 matched controls, RCC was associated with higher whole blood lead (OR=2.0, 95% CI:1.0,3.9; quartile 4 (Q4) v. Q1, Ptrend=0.022) and CALB1 rs1800645 (Ptrend=0.025, minor ‘T’ allele frequency=0.34). Higher total serum calcium (Ptrend=<0.001) was associated with reduced RCC risk. Total serum calcium and 25-hydroxyvitamin D levels did not alter the association observed with lead. Time from enrollment to RCC diagnosis was positively associated with serum calcium (Ptrend=0.002) and 25-hydroxyvitamin D (Ptrend=0.054) among cases.

Conclusions

Higher blood lead concentrations, below the 10 ug/dL level of concern, were associated with RCC, independent from serum calcium and CALB1 promoter polymorphism.

Impact

Increased risk of RCC is associated with lower serum calcium and higher whole blood lead in smokers. The clinical prognostic value of serum calcium and vitamin D in RCC should be further investigated.

Background

Numerous studies have documented the short-term impact of BRCA1/BRCA2 (BRCA1/2) testing; however, little research has examined the long-term impact of testing. We conducted the first long-term prospective study of psychosocial outcomes in a U.S. sample of women who had BRCA1/2 testing.

Methods

Participants were 464 women who underwent genetic testing for BRCA1/2 mutations. Prior to testing, we measured sociodemographics, clinical variables, and cancer specific and general distress. At long-term follow-up (Median=5.0 years; Range=3.4 to 9.1 years), we assessed cancer specific and genetic testing distress, perceived stress and perceived cancer risk. We evaluated the impact of BRCA1/2 test result and risk reducing surgery on long-term psychosocial outcomes.

Results

Among participants who had been affected with breast or ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β=0.41, P<0.0001), uncertainty (β=0.18, P<0.0001) and perceived stress (β=0.17, P=0.005) compared to women who received negative (i.e., uninformative) results. Among women unaffected with breast/ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β=0.39, P<0.0001) and lower positive testing experiences (β=0.25, P=0.008) than women with negative results. Receipt of risk-reducing surgery was associated with lower perceived cancer risk (P<0.0001).

Conclusions

In this first prospective long-term study in a U.S. sample, we found modestly increased distress in BRCA1/2 carriers compared to women who received uninformative or negative test results. Despite this modest increase in distress, we found no evidence of clinically significant dysfunction.

Impact

While a positive BRCA1/2 result remains salient among carriers years after testing, testing does not appear to impact long-term psychological dysfunction.

Background

Overexpression of mitotic kinases has been associated with prognosis, histologic grade and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined.

Methods

We measured associations between 397 single nucleotide polymorphisms (SNPs) from 67 mitotic kinases and invasive epithelial ovarian cancer risk in two case-control studies (n=671 cases; n=939 controls). Thirty-six candidate SNPs (p< 0.05) were assessed in a replication analysis consisting of three additional studies (n=1094 cases; n=829 controls).

Results

In initial analysis, thirty-six SNPs were suggestive of association with risk of serous ovarian cancer, all subtypes of ovarian cancer, or both (p<0.05). Replication analyses suggested an association between rs2125846 in the Nemo-like kinase gene (NLK) and ovarian cancer (serous odds ratio (OR)=1.36, 95% confidence interval (CI) 1.11 – 1.67, p=1.77 × 10−3; all subtypes OR=1.30, 95% CI 1.08 – 1.56, p=2.97 × 10−3). Furthermore, rs2125846 was associated with risk in the combined discovery and replication sets (serous OR=1.33, 95% CI 1.15 – 1.54; all subtypes OR=1.27, 95% CI 1.12 – 1.45).

Conclusions

Variation in NLK may be associated with risk of invasive epithelial ovarian cancer. Further studies are needed to confirm and understand the biological relationship between this mitotic kinase and ovarian cancer risk.

Impact

An association between SNPs in NLK and ovarian cancer may provide biological insight into the development of this disease.

Background

Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight.

Methods

We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2651 breast cancer cases and 2520 controls of African or European ancestry that were pooled from seven studies.

Results

We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk.

Conclusion

The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ancestry is likely weak, if it does exist.

Impact

The pleiotropic effects of known T2D risk alleles cannot explain the association between T2D and breast cancer risk.

Background

Telomeres protect chromosomal ends, shorten with cellular division, and signal cellular senescence but unchecked telomere attrition can lead to telomere dysfunction, upregulation of telomerase, and carcinogenesis. Shorter telomeres in peripheral blood leukocytes (PBLs) have been associated with elevated cancer risk. Further, genetic variants in and around the TERT gene have been implicated in carcinogenesis.

Methods

We measured relative telomere length (RTL) in PBLs of 911 cases and 948 controls from the New England Case Control Study, a population-based study of ovarian cancer. In addition, we assessed germline genetic variation in five telomere maintenance genes among 2112 cases and 2456 controls from the New England Case Control Study and the Nurses’ Health Study, a prospective cohort study. Odds ratios and 95% confidence intervals were estimated using logistic regression.

Results

Overall, we observed no differences in telomere length between cases and controls. Compared to women with RTL in the longest tertile, women with RTL in the shortest tertile had no increase in risk (OR=1.01, 95% CI: 0.80, 1.28). However, several SNPs in the TERT gene, including RS2736122, RS4246742, RS4975605, RS10069690, RS2736100, RS2853676, RS7726159, were significantly associated with ovarian cancer risk. We observed a significant gene-level association between TERT and ovarian cancer risk (p=0.00008).

Conclusion

Our observations suggest genetic variation in the TERT gene may influence ovarian cancer risk, but the association between average telomere length in PBLs and ovarian cancer remains unclear.

Impact

The role of telomeres in ovarian carcinogenesis remains unsettled and warrants further investigation.

Background

Calcium and vitamin D may be inversely related to breast cancer risk, in part by affecting mammographic density. However, results from previous, mostly cross-sectional studies have been mixed, and there have been few randomized clinical trials of the effect of calcium and vitamin D supplementation on change in mammographic density.

Methods

We assessed the effect of one year of supplementation on mammographic density in 330 postmenopausal women enrolled in the Women’s Health Initiative Hormone Therapy (HT) and Calcium and Vitamin D (CaD) trials. Women were randomized to receive 1000 mg/day of elemental calcium carbonate plus 400 IU/day of vitamin D3 or placebo.

Results

After approximately one year, mammographic density decreased 2% in the CaD supplementation group and increased 1% in the placebo group (ratio of means = 0.97; 95% confidence interval (CI) = 0.81–1.17). Results suggested potential interaction by HT use (P = 0.08). Among women randomized to HT placebo, the ratio of mean density comparing CaD supplementation and placebo groups was 0.82 (95%CI = 0.61–1.11) vs. 1.16 (95%CI = 0.92–1.45) in women randomized to active HT. In sensitivity analyses limited to women taking ≥80% of study supplements, ratios were 0.67 (95%CI = 0.41–1.07) in women not assigned to HT and 1.07 (95%CI = 0.79–1.47) women assigned to HT.

Conclusions

We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year.

Impact

Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study.

Background

Mesothelin is overexpressed in several malignancies and is purportedly a specific marker of malignant transformation. In this pilot study, we investigated whether tissue and serum mesothelin are potential markers of neoplastic progression in Barrett’s esophagus (BE) and in esophageal adenocarcinoma (EAC).

Methods

Mesothelin expression was retrospectively evaluated in normal, BE, and EAC tissue from surgically resected esophageal specimens (n = 125). In addition, soluble mesothelin-related peptide (SMRP) levels were measured in serum.

Results

Normal esophageal mucosa did not express mesothelin. BE tissue with high-grade dysplasia specifically expressed mesothelin, whereas BE tissue with low-grade or without dysplasia did not. Fifty-seven (46%) EAC tumors were positive for mesothelin. EAC tumors with BE expressed mesothelin more often than those without BE (58% vs 35%, P = 0.01). SMRP levels were elevated in 70% of EAC patients (mean, 0.89 nM; range, 0.03-3.77 nM), but not in patients with acid reflux and/or BE.

Conclusions

Mesothelin is commonly expressed in BE-associated esophageal adenocarcinoma. Based on this pilot study, a prospective study is under way to evaluate tissue and serum mesothelin are potential markers of neoplastic progression in BE and in EAC (NCT01393483).

Impact

Current surveillance methods in Barrett’s esophagus are invasive and neither cost-effective nor sensitive. This pilot study suggests that serum mesothelin is a marker of neoplastic transformation in BE and may provide a noninvasive method to improve identification of malignant transformation.

Background

We investigated associations between tobacco exposure, history of schistosomiasis and bladder cancer risk in Egypt.

Methods

We analyzed data from a case-control study (1,886 newly diagnosed and histologically confirmed cases and 2,716 age-, gender-, and residence-matched, population-based controls). Using logistic regression we estimated the covariate-adjusted odds ratios (OR) and 95% confidence interval (CI) of the associations.

Results

Among men, cigarette smoking was associated with an increased risk of urothelial carcinoma (UC) (OR = 1.8, 95% CI = 1.4, 2.2), but not squamous cell carcinoma (SCC); smoking both waterpipes and cigarettes was associated with an even greater risk for UC (OR = 2.9, 95% CI = 2.1, 3.9) and a statistically significant risk for SCC (OR = 1.8, 95% CI = 1.2, 2.6). Among non-smoking men and women, to environmental tobacco smoke exposure was associated with an increased risk of UC. History of schistosomiasis was associated with increased risk of both UC (OR = 1.9, 95% CI = 1.2, 2.9) and SCC (OR = 1.9, 95% CI = 1.2, 3.0) in women and to a lesser extent (OR = 1.4, 95% CI = 1.2, 1.7 and OR = 1.4, 95% CI = 1.1, 1.7, for UC and SCC respectively) in men.

Conclusions

The results suggest that schistosomiasis and tobacco smoking increase the risk of both SCC and UC.

Impact

This study provides new evidence for associations between bladder cancer subtypes and schistosomiasis, and suggests that smoking both cigarettes and waterpipes increases the risk for SCC and UC in Egyptian men.

Background

Persons with Barrett’s esophagus experience increased incidence of esophageal adenocarcinoma (EA) and may benefit from use of preventives. Studies suggest that statin medications may have chemopreventive properties; we therefore assessed the association between statin use and progression to EA.

Methods

In a prospective cohort of 411 persons with Barrett’s, Cox regression was used to calculate hazard ratios (HR) for NSAID and statin use accounting for variation in use during follow-up, and adjusting for age, sex, and smoking.

Results

The HRs for statin use among all participants were 0.59 (95% CI: 0.26–1.33) and 0.68 (95% CI: 0.30–1.54) before and after further adjustment for NSAID use, respectively. Among persons with high-grade dysplasia, the HRs for statin use were 0.31 (95% CI: 0.11–0.86) and 0.41 (95% CI: 0.13–1.26) before and after adding NSAIDs to the model, respectively.

Conclusions

While the reduced risk of EA observed among statin users may be explained by chance, the point estimates are similar in magnitude to those previously reported for NSAID use in this cohort, and are unlikely to be confounded by known risk factors.

Impact

Further study in larger cohorts and meta-analyses of the potential for statins to reduce risk of esophageal adenocarcinoma is warranted.

Background

Whether milk and dairy intake after a prostate cancer diagnosis is associated with a poorer prognosis is unknown. We investigated post-diagnostic milk and dairy intake in relation to risk of lethal prostate cancer (metastases and prostate cancer death) among participants in the Health Professionals Follow-Up Study.

Methods

The cohort consisted of 3,918 men diagnosed with apparently localized prostate cancer between 1986 and 2006, and followed to 2008. Data on milk and dairy intake were available from repeated questionnaires. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) of the association between post-diagnostic milk and dairy intake and prostate cancer outcomes.

Results

We ascertained 229 prostate cancer deaths and an additional 69 metastases during follow-up. In multivariate analysis, total milk and dairy intakes after diagnosis were not associated with a greater risk of lethal prostate cancer. Men with the highest versus lowest intake of whole milk were at an increased risk of progression (HR 2.15; 95% CI: 1.28-3.60; P trend<0.01). Men in the highest versus lowest quintile of low-fat dairy intake were at a decreased risk of progression (HR 0.62; 95% CI: 0.40-0.95; P trend=0.07).

Conclusions

With the exception of whole milk, our results suggest that milk and dairy intake after a prostate cancer diagnosis is not associated with an increased risk of lethal prostate cancer.

Impact

This is the first larger prospective study investigating the relation between post-diagnostic milk and dairy intake and risk of lethal prostate cancer.

Background

One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age.

Methods

We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.

Results

The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P=0.009), with highest accuracy in men younger than 60 years (C-statistic=0.679). The absolute ten-year risk for 50-year old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile).

Conclusions

Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening.

Impact

Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.

Background

Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Since colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women (Iowa Women’s Health Study [IWHS]).

Methods

The IWHS enrolled 41,836 randomly selected women, ages 55–69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs).

Results

PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95% CI = 0.66–1.06; p = 0.14) and KRAS mutation-positive (RR = 0.82; 95% CI = 0.58–1.16; p = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95% CI = 0.43–0.96; p = 0.03).

Conclusions

To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMH therapy. These data suggest that PMH therapy may reduce CRC risk through mechanisms beyond KRAS mutation status, but might provide greater benefits for KRAS mutation-negative than mutation-positive tumors (at least in the distal colorectum).

Impact

Findings from this prospective cohort study provide novel insights regarding the molecular biology of PMH therapy-related CRC risk reduction.

Background

Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biological mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to inter-individual differences in mammographic density measures.

Methods

We established an international consortium (DENSNP) of 19 studies from 10 countries, comprising 16,895 Caucasian women, to conduct a pooled cross-sectional analysis of common breast cancer susceptibility variants in 14 independent loci and mammographic density measures. Dense and non-dense areas, and percent density, were measured using interactive-thresholding techniques. Mixed linear models were used to assess the association between genetic variants and the square roots of mammographic density measures adjusted for study, age, case status, body mass index (BMI) and menopausal status.

Results

Consistent with their breast cancer associations, the C-allele of rs3817198 in LSP1 was positively associated with both adjusted dense area (p=0.00005) and adjusted percent density (p=0.001) whereas the A-allele of rs10483813 in RAD51L1 was inversely associated with adjusted percent density (p=0.003), but not with adjusted dense area (p=0.07).

Conclusion

We identified two common breast cancer susceptibility variants associated with mammographic measures of radio-dense tissue in the breast gland.

Impact

We examined the association of 14 established breast cancer susceptibility loci with mammographic density phenotypes within a large genetic consortium and identified two breast cancer susceptibility variants, LSP1-rs3817198 and RAD51L1-rs10483813, associated with mammographic measures and in the same direction as the breast cancer association.

BACKGROUND

Genetic influences may be discerned in families that have multiple affected members and may manifest as an earlier age of cancer diagnosis. In this study we determine whether cancers develop at an earlier age in multiplex Familial Barrett’s Esophagus (FBE) kindreds, defined by 3 or more members affected by Barrett’s esophagus (BE) or esophageal adenocarcinoma (EAC).

METHODS

Information on BE/EAC risk factors and family history was collected from probands at eight tertiary care academic hospitals. Age of cancer diagnosis and other risk factors were compared between non-familial (no affected relatives), duplex (two affected relatives), and multiplex (three or more affected relatives) FBE kindreds.

RESULTS

The study included 830 non-familial, 274 duplex and 41 multiplex FBE kindreds with 274, 133 and 43 EAC and 566, 288 and 103 BE cases, respectively. Multivariable mixed models adjusting for familial correlations showed that multiplex kindreds were associated with a younger age of cancer diagnosis (p = 0.0186). Median age of cancer diagnosis was significantly younger in multiplex compared to duplex and non-familial kindreds (57 vs. 62 vs. 63 yrs, respectively, p = 0.0448). Mean body mass index (BMI) was significantly lower in multiplex kindreds (p = 0.0033) as was smoking (p < 0.0001), and reported regurgitation (p = 0.0014).

CONCLUSIONS

Members of multiplex FBE kindreds develop EAC at an earlier age compared to non-familial EAC cases. Multiplex kindreds do not have a higher proportion of common risk factors for EAC, suggesting that this aggregation might be related to a genetic factor.

IMPACT

These findings indicate that efforts to identify susceptibility genes for BE and EAC will need to focus on multiplex kindreds.

Background

Vitamin D levels and calcium intake have been associated with risk of colorectal neoplasia, and genetic variation in vitamin D-pathway genes may affect circulating vitamin D metabolite concentrations and/or risk for colorectal lesions. This study evaluated associations between polymorphic variation in the Gc-globulin (GC) and Calcium-sensing receptor (CASR) and odds for metachronous colorectal neoplasia and vitamin D metabolite concentrations.

Methods

Participants from the Ursodeoxycholic Acid (UDCA) and Wheat Bran Fiber (WBF) trials (n=1439) were analyzed using a single nucleotide polymorphism (SNP) tagging approach, with a subset (n=404) of UDCA trial participants for whom vitamin D metabolite concentrations were also available. A total of 25 GC and 35 CASR tagSNPs were evaluated using multiple statistical methods.

Results

Principal components analyses did not reveal gene-level associations between GC or CASR and colorectal neoplasia, however, a significant gene-level association between GC and 25(OH)D concentrations (p < 0.01) was observed. At the individual SNP-level and following multiple comparisons adjustments, significant associations were observed between seven GC (rs7041, rs222035, rs842999, rs1155563, rs12512631, rs16846876, rs1746825) polymorphisms and circulating measures of 25(OH)D (adjusted p < 0.01), and CASR SNP rs1042636 and proximal colorectal neoplasia (adjusted p = 0.01).

Conclusions

These results demonstrate a possible association between variation in CASR and odds of colorectal neoplasia as well as the potential role of variation in GC with circulating 25(OH)D concentrations.

Impact

Additional research is warranted to determine the mechanism of GC genotype in influencing 25(OH)D concentrations and to further elucidate the role of CASR in colorectal neoplasia.

Background

A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention.

Methods

We pooled data from 12 case-control studies including 6,448 cases and 13,747 controls, and estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use and body mass index (BMI).

Results

We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI, 0.95–1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI, 1.22–2.07), and no association among ever smokers (OR, 0.96; 95% CI, 0.83–1.11); likelihood ratio test for interaction p=0.001.

Conclusions

A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes.

Impact

This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC.

BACKGROUND

Coffee has been hypothesized to have pro- and anti-carcinogenic properties, while tea may contain anti-carcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, while findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (abbreviated as SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous.

METHODS

In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random effects model.

RESULTS

No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR=1.10, 95% CI=0.81-1.48 comparing ≥900 to <0g/day; 237g≈8oz), tea (MVRR=0.96, 95% CI=0.78-1.16 comparing ≥400 to 0g/day; 237g≈8oz) or SSB (MVRR=1.19, 95% CI=0.98-1.46 comparing ≥250 to 0g/day; 355g≈12oz) (p-value, test for between-studies heterogeneity >0.05). These associations were consistent across levels of sex, smoking status and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR=1.06, 95% CI=1.02-1.12).

CONCLUSION AND IMPACT

Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.

Background

Effective breast cancer screening and early detection are crucial for obese women, who experience a higher incidence of the disease and present at later stages.

Methods

We examined the association between body mass index (BMI) and timeliness of follow-up after 241,222 abnormal screening mammograms performed on 201,470 women in the Breast Cancer Surveillance Consortium. Each mammogram had one of three recommendations for follow-up: short-interval follow-up; immediate additional diagnostic imaging; and biopsy/surgical consultation. We used logistic regression to estimate the adjusted effect of BMI on any recorded follow-up within 270 days of the recommendation; linear regression was used to model the mean follow-up time among those with recorded follow-up.

Results

As compared to normal-weight women, higher BMI was associated with slightly increased odds of follow-up among women who received a recommendation for short-interval follow-up (odds ratios (ORs) 1.03–1.10; p=0.04) or immediate additional imaging (ORs 1.03–1.09; p=0.01). No association was found for biopsy/surgical consultation recommendations (p=0.90). Among those with recorded follow-up, higher BMI was associated with longer mean time to follow-up for both short-interval (3–10 days; p<0.001) and additional imaging recommendations (2–3 days; p<0.001), but not biopsy/surgical consultation (p=0.06). Regardless of statistical significance, actual differences in days to follow-up across BMI groups were small and unlikely to be clinically significant.

Conclusions

Once obese women access screening mammography, their follow-up after abnormal results is similar to that of normal-weight women.

Impact

Efforts to improve early detection of breast cancer in obese women should focus elsewhere, such as improving participation in screening mammography.

Biospecimens are recognized as critical components of biomedical research, from basic studies, to clinical trials and epidemiologic investigations. Biorepositories have existed in various forms for over 150 years, from early small collections in pathology laboratories to modern automated facilities managing millions of samples. As collaborative science has developed it has been recognized that biospecimens must be of consistent quality. Recent years have seen a proliferation of best practices and the recognition of the field of “biospecimen science.” The future of this field will depend on the development of more evidence-based practices in both the research and clinical settings. As the field matures, educating a new generation of biospecimen/biobanking scientists will be an important need.

Background

Increasing colorectal cancer screening (CRCS) is important for attaining the Healthy People 2020 goal of reducing CRC-related morbidity and mortality. Evaluating CRCS trends can help identify shifts in CRCS, as well as specific groups that might be targeted for CRCS.

Methods

We utilized medical records to describe population-based adherence to average-risk CRCS guidelines from 1997-2008 in Olmsted County, MN. CRCS trends were analyzed overall and by gender, age, and adherence to screening mammography (women only). We also performed an analysis to examine whether CRCS is being initiated at the recommended age of 50.

Results

From 1997-2008, the size of the total eligible sample ranged from 20585 to 21468 people. CRCS increased from 22% to 65% for women and from 17% to 59% for men (p<0.001 for both) between 1997 and 2008. CRCS among women current with mammography screening increased from 26% to 74%, and this group was more likely to be adherent to CRCS than all other subgroups analyzed (p<0.001).The mean ages of screening initiation were stable throughout the study period, with a mean age of 55 years among both men and women in 2008.

Conclusions

While overall CRCS tripled during the study period, there is still room for improvement.

Impact

Working to decrease the age at first screening, exploration of gender differences in screening behavior, and targeting women adherent to mammography but not to CRCS appear warranted.

Background

The study objectives were to compare and examine mammography use trends among ethnic/racial women in the context of United States Healthy People 2010 goals.

Methods

We analyzed pooled, multistage probability sample data from the 1996–2007 Medical Expenditure Panel Survey. Included in the sample were female respondents ages 40–75 years (n=64,811) from six ethnic/racial groups (Black, White, Mexican, Other Latinas, Puerto Rican and Cuban). The primary outcome was self-reported, past two-year mammography use consistent with screening practice guidelines.

Results

We found that for most U.S. women, the Healthy People 2010 mammography goal (70%) was achieved between 1996 and 2007. Puerto Rican and White women, respectively, had the highest mammography rates, and Black and Cuban women had rates that approached the 2010 goal.

Conclusion

Mexican Latinas reported the lowest rates of past two-year mammography; however, factors enabling healthcare access markedly moderated this lower likelihood. From 2000, Mexican Latinas’ mammography use was markedly below (10%) the Healthy People 2010 goal and remained there for the duration.

Impact

Our findings indicate that healthcare equity goals are attainable if efforts are made to reach a sizeable portion of vulnerable populations.

Background

We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.

Methods

IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.

Results

Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 [Hazard ratio (HR) = 1.43; 95% CI: 1.06–1.92; p = 0.019] and BRCA2 mutation carriers (HR=2.21; 95% CI: 1.39–3.52, p=0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class 2 mutations than class 1 (mutations (class 2 HR=1.86, 95% CI: 1.28–2.70; class 1 HR=0.86, 95%CI:0.69–1.09; p-for difference=0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class 2 mutation carriers (HR = 2.42; p = 0.03).

Conclusion

The IRS1 Gly972Arg SNP, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class 2 mutation carriers.

Impact

These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.

Background

Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of post-diagnostic weight variation on survival, we examined the relationship by comorbid status and initial BMI.

Methods

The current analysis included 12,915 breast cancer patients diagnosed between 1990 and 2006 with Stage I–III tumors from four prospective cohorts in the US and China Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of five weight change categories (within <5% [reference]; 5–<10% and ≥10% loss and gain) with mortality were estimated using Cox proportional hazards models.

Results

Mean weight change was 1.6 kg. 14.7% of women lost and 34.7% gained weight. Weight stability in the early years post-diagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR=1.41; 95% CI: 1.14, 1.75) in the US and over three times the risk of death (HR=3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by pre-diagnosis BMI, and in the US lower survival were seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a non-significant increased risk of death.

Conclusions

Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality.

Impact

Weight control strategies for breast cancer survivors should be personalized to the individual’s medical history.