Perceived risk of breast cancer among Latinas attending community clinics: risk comprehension and relationship with mammography adherence

Objective  To describe breast cancer risk perceptions, determine risk comprehension, and evaluate mammography adherence among Latinas. Methods  Latina women age ≥35, primarily from Central and South America, were recruited from community-based clinics to complete in-person interviews (n = 450). Risk comprehension was calculated as the difference between numeric perceived risk and Gail risk score. Based on recommended guidelines from the year data were collected (2002), mammography adherence was defined as having a mammogram every one to two years for women ≥40 years of age. Results  Breast cancer risk comprehension was low, as 81% of women overestimated their risk and only 6.9% of women were high risk based on Gail risk scores. Greater cancer worry and younger age were significantly associated with greater perceived risk and risk overestimation. Of women age eligible for mammography (n = 328), 29.0% were non-adherent to screening guidelines. Adherence was associated with older age, (OR = 2.99, 95% CI = 1.76–5.09), having insurance (OR = 1.81, 95% CI = 1.03–3.17), greater acculturation (OR = 1.18, 95% CI = 1.02–1.36), and higher breast cancer knowledge (OR = 2.03, 95% CI = 1.21–3.40). Conclusions  While most Latinas over-estimated their breast cancer risk, older age, having insurance, being more acculturated, and having greater knowledge were associated with greater screening adherence in this Latino population. Perceived risk, risk comprehension, and cancer worry were not associated with adherence. In Latinas, screening interventions should emphasize knowledge and target education efforts at younger, uninsured, and less acculturated mammography-eligible women. Supported by Grants U01CA86114, U01CA114593, K05CA96940 (JM), and K07CA131172 (KG) from the National Cancer Institute.     

Current evidence on the relationship between HRAS1 polymorphism and breast cancer risk: a meta-analysis

Several molecular epidemiological studies were conducted in recent years to evaluate the association between NQO1 Pro187Ser polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 3177 cases with breast cancer and 4038 controls from seven published case–control studies showed that the 187Ser allele was not associated with a significantly increased risk of breast cancer (Ser versus Pro: P = 0.33, OR = 1.08, 95% CI = 0.92–1.28; Ser/Ser versus Pro/Pro: P = 0.58, OR = 1.16, 95% CI = 0.68–2.00; Ser/Ser versus Pro/Ser + Pro/Pro: P = 0.62, OR = 1.14, 95% CI = 0.68–1.90; Ser/Ser + Pro/Ser versus Pro/Pro: P = 0.30, OR = 1.07, 95% CI = 0.94–1.22). In the stratified analysis by ethnicity, we found that the Pro187Ser polymorphism was associated with increased breast cancer risk in Caucasians in the additive genetic model and dominant genetic model (P = 0.03, OR = 1.13, 95% CI = 1.01–1.26; P = 0.03, OR = 1.15, 95% CI = 1.01–1.30, respectively), whereas no significant in Asians (P = 0.44, OR = 0.94, 95% CI = 0.80–1.10) and postmenopausal women (P = 0.99, OR = 1.00, 95% CI = 0.84–1.19). The results suggest that NQO1 Pro187Ser polymorphism may contribute to breast cancer development in Caucasians.     

State vocational services and employment in cancer survivors

Background  This study investigated the association of state vocational rehabilitation services in the USA and work outcomes of cancer survivors who were unemployed prior to receipt of services. Methods  Administrative data obtained during fiscal year 2005 from the Rehabilitation Services Administration (RSA) database consisting of 1,201 closed cases with the diagnosis of cancer formed the sample of this study. All cancer survivors were unemployed at the time of application. Data on demographic characteristics, employment and vocational service variables were extracted and analyzed in relation to employment outcome data. Multivariate logistic regression was used to examine the relationship among services provided and work outcomes accounting for demographic characteristics of the participants. Results  Cancer survivors represented 0.4% of the total population that received vocational services in the state-federal vocational rehabilitation program. Of the unemployed cancer survivors who received services, 903 (57%) achieved successful employment while 670 (43%) were not employed following receipt of services. Gender (women; OR = 0.77, 95% CI = 0.61–0.97), lower educational levels (OR = 0.52, 95% CI = 0.33–0.81), provision of cash or medical benefits (e.g., Social Security Disability Insurance benefits; OR = 0.64, 95% CI = 0.50–0.82) were all associated with a greater likelihood of being unemployed at the end of vocational services. Counseling (OR = 1.33, 95% CI = 1.02–1.73), miscellaneous training (OR = 1.61, 95% CI = 1.06–2.44), rehabilitation technology services (OR = 1.22, 95% CI = 0.72–2.08), job placement services (OR = 2.37, 95% CI = 1.72–3.27), job search assistance (OR = 1.43; 95% CI = 1.02–2.01) maintenance services (OR = 1.92, 95% CI = 1.29–2.86), and other services (OR = 1.43, 95% CI = 1.07–1.90) were found to be significantly associated with increased odds for employment. Conclusion  Vocational rehabilitation services were found to be associated with employment status. Future studies investigating the specific effects of certain vocational services for unemployed cancer survivors who qualify for these services are warranted. Implications for cancer survivors  Cancer survivors who are seeking employment or experiencing problems maintaining employment who can qualify should be encouraged to pursue services from state vocational rehabilitation agencies. Medical providers should also become familiar with services offered by state vocational rehabilitation agencies and consider the use of these services..     

Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry

The distribution of breast cancer molecular subtypes has been shown to vary by race/ethnicity, highlighting the importance of host factors in breast tumor biology. We undertook the current analysis to determine population-based distributions of breast cancer subtypes among six ethnic Asian groups in California. We defined immunohistochemical (IHC) surrogates for each breast cancer subtype among Chinese, Japanese, Filipina, Korean, Vietnamese, and South Asian patients diagnosed with incident, primary, invasive breast cancer between 2002 and 2007 in the California Cancer Registry as: hormone receptor-positive (HR+)/HER2− [estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-negative (HER2−)], triple-negative (ER−, PR−, and HER2−), and HER2-positive (ER±, PR±, and HER2+). We calculated frequencies of breast cancer subtypes among Asian ethnic groups and evaluated their associations with clinical and demographic factors. Complete IHC data were available for 8,140 Asian women. Compared to non-Hispanic White women, Korean [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.5–2.2], Filipina (OR = 1.3, 95% CI = 1.2–1.5), Vietnamese (OR = 1.3, 95% CI = 1.1–1.6), and Chinese (OR = 1.1, 95% CI = 1.0–1.3) women had a significantly increased risk of being diagnosed with HER2-positive breast cancer subtypes after adjusting for age, stage, grade, socioeconomic status, histology, diagnosis year, nativity, and hospital ownership status. We report a significant ethnic disparity in HER2-positive breast cancer in a large population-based cohort enriched for Asian-Americans. Given the poor prognosis and high treatment costs of HER2-positive breast cancer, our results have implications for healthcare resource utilization, cancer biology, and clinical care.     

Outcome of axillary staging in early breast cancer: a meta-analysis

Axillary lymph node dissection (ALND) is associated with significant morbidity, whilst sentinel node biopsy (SNB) has the potential to minimize complications in the management of breast cancer. The aim of this study was to systematically appraise the outcome of SNB when compared to ALND. A comprehensive search for published trials examining outcomes after SNB for breast cancer was performed using medline and cross-referencing available data. Each study was reviewed and data extracted. Primary outcomes were nodal positivity and surgery-related morbidity. A total of 9,608 patients were identified from trials comparing ALND and SNB. The overall rate of axillary lymph node positivity for those with no clinically palpable nodes was 28.8% for ALND and 27.6% for SNB (OR = 1.00, 95% CI = 0.86–1.17, P = 0.956), though there was a trend for superior detection of metastatic disease with SNB when this was compared with ALND alone (OR = 1.22, 95% CI = 0.95–1.57, P = 0.122). Patients who undergo SNB are significantly less likely to suffer post-operative morbidity relative to ALND: risk of infection (OR = 0.58, 95% CI = 0.42–0.80, P = 0.0011), seroma (OR = 0.40, 95% CI = 0.31–0.51, P = 0.0071), arm swelling (OR = 0.30, 95% CI = 0.14–0.66, P = 0.0028) and numbness (OR = 0.25, 95% CI = 0.1–0.59, P = 0.0018). SNB is at least equivalent to ALND in detecting metastatic disease in the axilla. SNB is the optimum approach in terms of morbidity for the assessment of axillary metastasis in clinically node negative breast cancer.     

Breast cancer risk assessment in women aged 70 and older

Although the benefit of screening mammography for women over 69 has not been established, it is generally agreed that screening recommendations for older women should be individualized based on health status and breast cancer risk. However, statistical models to assess breast cancer risk have not been previously evaluated in this age group. In this study, the original Gail model and three more recent models that include mammographic breast density as a risk factor were applied to a cohort of 19,779 Vermont women aged 70 and older. Women were followed for an average of 7.1 years and 821 developed breast cancer. The predictive accuracy of each risk model was measured by its c-statistic and associations between individual risk factors and breast cancer risk were assessed by Cox regression. C-statistics were 0.54 (95% CI = 0.52–0.56) for the Gail model, 0.54 (95% CI = 0.51–0.56) for the Tice modification of the Gail model, 0.55 (95% CI = 0.53–0.58) for a model developed by Barlow and 0.55 (95% CI = 0.53–0.58) for a Vermont model. These results indicate that the models are not useful for assessing risk in women aged 70 and older. Several risk factors in the models were not significantly associated with outcome in the cohort, while others were significantly related to outcome but had smaller relative risks than estimated by the models. Age-related attenuation of the effects of some risk factors makes the prediction of breast cancer in older women particularly difficult.     

The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis

It was reported that the functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase gene was associated with breast cancer risk; however, the published studies have inconsistent conclusions. To elucidate the effect of hOGG1 Ser326Cys on the susceptibility to breast cancer, all available studies were collected in this meta-analysis. We extracted the data from 10 case–control studies that were published in the PubMed database from 2003 to 2008 using the search phrases “human 8-oxoguanine DNA glycosylase, hOGG1, OGG1, OGG, polymorphism, genetic variation, and breast cancer.” This meta-analysis included 4,963 breast cancer cases and 4,776 control subjects. The results showed that individuals who carrying the hOGG1 326Cys allele in the additive model did not have significantly increased risk of breast cancer compared with those carrying the 326Ser allele (P = 0.47, OR = 1.02; 95% CI = 0.96–1.09); similarly, no significant association between the hOGG1 326Cys allele and breast cancer risk was found either in the recessive genetic model (P = 0.34, OR = 1.06; 95% CI = 0.94–1.18) for Cys/Cys versus Ser/Cys + Ser/Ser, or dominant genetic model (P = 0.78, OR = 1.01; 95% CI = 0.93–1.11) for Cys/Cys + Ser/Cys versus Ser/Ser. In the stratified analysis, the meta-analysis showed the association between hOGG1 326Cys allele in the additive model and breast cancer was significant in European subjects (P = 0.04, OR = 0.71; 95% CI = 0.51–0.98), and dominant genetic model (P = 0.004, OR = 0.44; 95% CI = 0.25–0.77). However, the association was not significant between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (Asians and Americans). The meta-analysis suggested that the hOGG1 326Cys allele plays a significant protective effect to breast cancer in European women.     

IGFBP3 A-202C polymorphism and breast cancer susceptibility: a meta-analysis involving 33,557 cases and 45,254 controls

Published data on the association between insulin-like growth factor binding protein 3 (IGFBP3) A-202C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 27 studies including 33,557 cases and 45,254 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with IGFBP3 C allele when all studies were pooled into the meta-analysis (CC vs. AA: OR = 1.06, 95% CI = 1.02–1.11; dominant model: OR = 1.04, 95% CI = 1.00–1.07). In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (AC vs. AA: OR = 1.04, 95% CI = 1.00–1.08; CC vs. AA: OR = 1.05, 95% CI = 1.01–1.10; dominant model: OR = 1.04, 95% CI = 1.00–1.08) and Asians (CC vs. AA: OR = 1.35, 95% CI = 1.02–1.78; recessive model: OR = 1.38, 95% CI = 1.05–1.82). When stratified by study design, statistically significantly elevated risk was found among population-based studies (CC vs. AA: OR = 1.06, 95% CI = 1.01–1.11; dominant model: OR = 1.03, 95% CI = 1.00–1.07). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. In conclusion, this meta-analysis suggests that the IGFBP3 C allele is a low-penetrant risk factor for developing breast cancer.     

Abstracting height and weight from medical records, and breast cancer pathologic factors

Cancer registries routinely collect data on clinicopathologic factors, but rarely abstract anthropometric variables. We conducted a chart review study, examining the feasibility of abstracting weight, height, alcohol use, and smoking from medical records in women (n = 1,974) diagnosed with invasive breast cancer, and investigated the association between the abstracted variables with clinicopathologic features. Qualitative data were reviewed and categorized. Frequencies of the abstracted data, and demographic and clinicopathologic variables were calculated. Logistic regression models measured the relationship between the outcome variables, tumor size, stage of disease, and estrogen/progesterone (ER/PR) status with the abstracted variables. Data on current alcohol-use/no-use, current-smoker/non-smoker, and height/weight data were obtained on 96%, 97%, and 88–89% of the participants, respectively. The multivariate analysis showed that overweight (≥25 kg/m²) women had significantly larger (≥2 cm) tumor size compared with normal weight for both women <50 years (OR = 1.79; 95% CI = 1.14–2.81; p ≤ 0.05) and for women ≥50 years at diagnosis (OR = 1.58; 95% CI = 1.19–2.09; p ≤ 0.05). These results suggest that abstracting current height and weight via medical records is feasible, and at minimum, current alcohol use and smoking status can be ascertained. In addition, being overweight was significantly associated with cancer clinicopathologic/prognostic factors, which has implications for monitoring etiologic factors that could be associated with cancer trends, incidence, and survival. Therefore routine collection of height and weight via cancer registries should be explored further.     

No significant association between the TP53 codon 72 polymorphism and breast cancer risk: a meta-analysis of 21 studies involving 24,063 subjects

Conflicting data have been published as to the possible association between polymorphism in codon 72 of the TP53 tumor suppressor gene and the risk of developing breast cancer. In order to address this question, we carried out a meta-analysis of 21 studies of and this polymorphism and breast cancer risk, which collectively included 12,601 cases and 11,462 controls. Studies were identified by searching the Medline, PubMed, Embase, and ISI Web of Knowledge databases. The strength of association between the TP53 codon 72 polymorphism and breast cancer risk was assessed by calculating crude OR values with 95% CIs, with pooled OR values calculated separately for three genetic inheritance models. We found no significant association between TP53 codon 72 polymorphism and breast cancer risk for either the codominant inheritance model (Pro/Arg vs. Pro/Pro: OR = 1.063, 95% CI = 0.967–1.169; Arg/Arg vs. Pro/Pro: OR = 1.245, 95% CI = 0.997–1.554), the dominant model (OR = 1.146, 95% CI = 0.979–1.340), or the recessive model (OR = 1.179, 95% CI = 1.020–1.362). Stratified analysis by ethnicity and source of controls similarly revealed no significant association for any of the genetic models. In summary, this meta-analysis provides strong evidence that the TP53 codon 72 polymorphism is not associated with the risk of developing breast cancer.     

Association between CYP19 polymorphisms and breast cancer risk: results from 10,592 cases and 11,720 controls

The association of CYP19 gene polymorphisms with breast cancer has been widely reported, but results of previous studies were somewhat contradictory and underpowered. In order to overcome the limitations of individual study and to understand the real situation, we conducted a systematic review and meta-analysis including three CYP19 gene polymorphisms [R264C polymorphism, CYP19_630 3-bp del/Ins polymorphism, and CYP19_681 (TTTA)_n polymorphisms]. A total of 22 studies with 10,592 cases and 11,720 controls were identified, and the results showed that R264C polymorphism was not associated with breast cancer risk in overall (T vs. C: OR = 1.061, 95% CI = 0.929–1.212) or race-based populations (T vs. C for Asian: OR = 1.169, 95% CI = 1.002–1.363; for Caucasian: OR = 0.787, 95% CI = 0.597–1.037); meanwhile, for Asian individuals, 3-bpDel/Ins polymorphism showed a significantly association with breast cancer susceptibility (for allele Del vs. allele Ins: OR = 1.278, 95% CI = 1.066–1.532) while the carriers of allele (TTTA)₁₂ can significantly decrease breast cancer risk (OR = 0.752, 95% CI = 0.603–0.939). Furthermore, the carriers of allele (TTTA)₁₀ were significantly associated with breast cancer susceptibility (OR = 1.515, 95% CI = 1.115–2.058). It can be concluded that potentially functional CYP19_630 3-bp del/Ins polymorphism and CYP19_681 (TTTA)_n polymorphisms may play a low penetrance role in breast cancer susceptibility in an ethnicity-specific manner.     

Risk factors for lymphedema in breast cancer survivors, the Iowa Women's Health Study

Risk factors for lymphedema and related arm symptoms in breast cancer (BC) survivors have not been examined using a large prospective population-based cohort. The Iowa Women’s Health Study (IWHS) collected self-reported data for diagnosed lymphedema in 2004, and data for cancer diagnosis, treatment, behavioral and health characteristics between 1986 and 2003. We studied 1,287 women, aged 55–69 at baseline, who developed unilateral BC: n = 104 (8%) with diagnosed lymphedema, n = 475 (37%) with arm symptoms but without diagnosed lymphedema, and n = 708 without lymphedema. Age- and multivariate-adjusted logistic regression models examined risk factors for lymphedema and related arm symptoms (OR [95% confidence interval]). The mean time between BC and the 2004 survey was 8.1 ± 5.0 (mean ± SD) years. After multivariate adjustment, the following cancer characteristics were positively associated with lymphedema: tumor stage (regional vs. in situ: 3.92 [1.61–9.54]), number of excised nodes (highest vs. lowest quintile: 3.52 [1.32–9.34], P _trend = 0.003), tumor-positive nodes (yes vs. no 2.12 [1.19, 3.79]), and adjuvant chemotherapy (yes vs. no: 3.05 [1.75–5.30]). Several health characteristics were positively associated with lymphedema: baseline body mass index (highest vs. lowest tertile: 3.24 [1.70–6.21]), waist and hip circumference, and general health (fair/poor vs. excellent: 3.44 [1.30–9.06]). Positive associations with arm symptoms were number of excised nodes (highest vs. lowest quintile: 2.38 [1.41–4.03], P _trend = 0.007), axillary radiation (yes vs. no: 1.72 [1.15–2.57]), and baseline general health (fair/poor vs. excellent: 4.27 [2.60–7.00]). In the IWHS, obesity, poorer general health, and markers of more advanced cancer were risk factors for lymphedema and related arm symptoms in BC survivors.     

MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls

Published data on the association between MTHFR C677T polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR C677T polymorphism and breast cancer risk. The pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A total of 37 studies including 15,260 cases and 20,411 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TT variant genotype in homozygote comparison and dominant genetic model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11, 95% CI = 1.01–1.23; dominant model: OR = 1.04, 95% CI = 1.00–1.09). In the subgroup analysis by ethnicity, significantly increased risks were found for TT allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04–1.35; recessive model: OR = 1.15, 95% CI = 1.03–1.29). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TT vs. CC: OR = 1.18, 95% CI = 1.02–1.38; recessive model: OR = 1.17, 95% CI = 1.05–1.29). In the subgroup analysis by menopausal status, statistically significantly increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI = 1.02–1.23; dominant model: OR = 1.11, 95% CI = 1.01–1.22). In conclusion, this meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for developing breast cancer.     

HER2 Ile655Val polymorphism contributes to breast cancer risk: evidence from 27 case–control studies

Proto-oncogene HER2 (also known as erbB-2 or neu) plays an important role in the carcinogenesis and the prognosis of breast cancer. Many epidemiological studies have been conducted to explore the association between the HER2 Ile655Val polymorphism and breast cancer risk. However, inconsistency existed in the results. Therefore, we performed a meta-analysis of 27 published case–control studies including 11,504 cases and 12,538 controls. We assessed the strength of the association by crude odds ratios (ORs) with 95% confidence intervals (CIs) and reached a result that HER2 Ile655Val polymorphism was associated with an increased breast cancer risk in overall populations (for Ile/Val vs. Ile/Ile: OR = 1.05, 95% CI = 1.00–1.12, P = 0.07 for heterogeneity; for the dominant model Ile/Val + Val/Val vs. Ile/Ile: OR = 1.10, 95% CI = 1.01–1.20, P = 0.01 for heterogeneity). In subgroup analysis by ethnicity, we found a significant association among Africans (for Val/Val vs. Ile/Ile: OR = 8.78, 95% CI = 1.94–39.72, P = 0.35 for heterogeneity; for the recessive model Val/Val vs. Ile/Val +Ile/Ile: OR = 8.60, 95% CI = 1.92–38.48, P = 0.31 for heterogeneity) and Asians (for Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01–1.39, P = 0.41 for heterogeneity; for the dominant model Val/Val + Ile/Val vs. Ile/Ile: OR = 1.18, 95% CI = 1.01–1.38, P = 0.27 for heterogeneity). In conclusion, our meta-analysis suggests that HER2 Ile 655Val polymorphism may contribute to breast cancer risk.     

The association between two polymorphisms of eNOS and breast cancer risk: a meta-analysis

Breast cancer is one of the most common malignant tumors worldwide. Endothelial nitric oxide synthase (eNOS) plays a key role in breast cancer development. The associations between the two eNOS polymorphisms (E298D rs1799983, −786T>C rs2070744) and breast cancer risk are inconclusive. A meta-analysis was performed in this study. By searching Medline, ISI Web of Knowledge, ScienceDirect, EBSCO, CNKI, and SinoMed database, six case–control studies were collected for the eNOS E298D polymorphism (3,038 cases and 2,508 controls) and three case–control studies were eligible for the eNOS −786T>C polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the two eNOS polymorphisms and breast cancer risk. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Overall, significantly decreased risk was observed for E298D (for EE vs. DD: OR = 0.74, 95% CI = 0.59–0.94; for ED vs. DD: OR = 0.78, 95% CI = 0.61–0.98; for dominant model: OR = 0.77, 95% CI = 0.61–0.96) and −786T > C (for TT vs. CC: OR = 0.60, 95% CI = 0.42–0.86; for dominant model: OR = 0.66, 95% CI = 0.47–0.94). In the subgroup analysis by ethnicity, significant decreased risks were found for E298D (for EE vs. DD: OR = 0.75, 95% CI = 0.56–0.99) and −786T>C (for TT vs. CC: OR = 0.53, 95% CI = 0.35–0.81; for dominant model: OR = 0.61, 95% CI = 0.41–0.91; for recessive model: OR = 0.70, 95% CI = 0.55–0.91) among Caucasians; significant decreased risks were observed for E298D (for ED vs. DD: OR = 0.12, 95% CI = 0.02–0.96; for dominant model: OR = 0.13, 95% CI = 0.02–1.00) among Asians. In conclusion, this meta-analysis suggests that both eNOS E298D and −786T>C polymorphisms are associated with reduced breast cancer risk.     

Comorbidities, therapy, and newly diagnosed conditions for women with early stage breast cancer

Purpose  To describe comorbidities in breast cancer patients at diagnosis and examine factors associated with self-reported comorbidities 30 months post-diagnosis. Methods  Nine hundred forty one of 1,171 women had a medical record abstract and a follow-up survey in the Health, Eating, Activity and Lifestyle Study. Results  We compared our breast cancer cohort to a contemporaneous nationally-representative sample of age, race/ethnicity and education matched women without cancer (n = 865). Breast cancer patients did not have substantially more comorbidities than women without breast cancer. Women with a hospital record of congestive heart failure significantly less often received chemotherapy or radiation following breast conserving surgery. In multivariate analysis, women who received chemotherapy alone (OR = 3.2; 95% CI: 1.5–6.8), chemotherapy plus radiation (OR = 1.9; 95% CI: 1.02–3.7) or radiation plus tamoxifen (OR = 1.9; 95% CI: 1.1–3.2) were significantly more likely to report at least one new comorbid condition following breast cancer diagnosis than women who received no chemotherapy, tamoxifen or radiation. Overall, women who received adjuvant therapy were more likely to have new comorbidities. Conclusions  Comorbidities were not substantially different in breast cancer patients than the non-cancer matched controls. Future research should focus on efforts to minimize comorbidities related to chemotherapy and other combination therapy. Funding source  N01-PC-35139, N01-PC-35142, N01-PC-35138     

A polymorphism in Werner syndrome gene is associated with breast cancer susceptibility in Chinese women

RecQ helicases play a central role in maintaining genome stability and may interact with some important cancer-related proteins such as BRCA1. Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature aging and cancer predisposition, including breast cancer. In this case–control study of 1,004 breast cancer cases and 1,008 controls, we tested the hypothesis that non-conservative amino acid exchanges in WRN (leu1074Phe), BLM (Met298Thr) and BRCA1 (Pro871Leu) are independently or jointly associated with the risk of breast cancer in Chinese women. We found that the variant genotype of WRN Leu1074Phe was associated with a 1.36-fold significantly increased risk of breast cancer (OR = 1.36, 95% CI = 1.06–1.74). Moreover, a significant gene–environment interaction was evident between WRN leu1074Phe and age at menarche (P _int = 0.02). Subjects carrying Phe/Phe genotype and with earlier age at menarche had 3.58-fold increased risk of breast cancer (OR = 3.58, 95% CI = 2.54–5.05). However, we did not find the significant main effect of polymorphisms in BLM and BRCA1 and also no locus–locus interactions were identified between WRN, BLM and BRCA1. These findings indicate that WRN leu1074Phe variant may contribute to the susceptibility of breast cancer in Chinese women.     

Association between the p53 polymorphisms and breast cancer risk: meta-analysis based on case–control study

p53 is a tumor suppressor gene and plays an important role in the etiology of breast cancer. However, studies on the association between p53 polymorphisms and breast cancer risk have yielded conflicting results. We performed a meta-analysis to investigate the association between breast cancer and the p53 polymorphisms codon 72 (27,046 cases and 30,998 controls), IVS3 16 bp (3,332 cases and 3,700 controls) and IVS6+62A>G (8,787 cases and 9,869 controls) in different inheritance models. When all the eligible studies of codon 72 polymorphism were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and p53 codon 72 polymorphism in any genetic model. However, in the stratified analysis for Indian population, significantly association was observed in additive model (OR = 0.62, 95% CI = 0.46–0.82, P value of heterogeneity test [P _h] = 0.153) and recessive model (OR = 0.70, 95% CI = 0.50–0.92, P _h = 0.463). IVS3 16 bp was significantly associated with breast cancer risk in a pooled 15 studies dataset (dominant model: OR = 1.14, 95% CI = 1.02–1.27, P _h = 0.30; recessive model: OR = 1.61, 95% CI = 1.21–2.25, P _h = 0.25; additive model: OR = 1.66, 95% CI = 1.24–2.21, P _h = 0.28). No significant association was found between IVS6+62A>G polymorphism and breast cancer risk in a total of 14 studies. In summary, these results indicate that IVS3 16 bp is likely an important genetic marker contributing to susceptibility of breast cancer, and codon 72 homozygous mutants may be associated with decreased breast cancer risk in Indian population.     

Effects of life event stress and social support on the odds of a ≥2 cm breast cancer

Objective  To examine the contribution of life event and social support factors to diagnosis with a ≥2 cm breast cancer. Methods  We studied 1,459 Australian women aged 40–69 diagnosed in 2002–2003 with a first primary invasive breast cancer 1.1 cm or larger. We measured stressful life events, perceived stress levels, and social support in the year before diagnosis and collected information on other potential risk factors and confounders. Results  The odds of a ≥2 cm breast cancer relative to a 1.1–1.9 cm breast cancer were reduced in women who reported tension or change in an intimate relationship in the year before diagnosis (OR = 0.71 95% CI 0.54–0.92; p = 0.009); the reduction was greatest in women living with a partner (OR = 0.64 95% CI 0.47–0.88; p = 0.006) and was largely unaffected by adjustment for other variables independently associated with a ≥2 cm breast cancer in our study. There was no evidence that the total number or severity of all studied life events influenced cancer size. Low partner support increased the odds of a ≥2 cm cancer but only in women not living with a partner. Conclusion  Intimate relationship stress may reduce risk of a ≥2 cm breast cancer. Suppression by stress of estrogen synthesis and metabolism is a possible mechanism.     

Diabetes and risk of pancreatic cancer: a pooled analysis of three large case–control studies

Racial differences in diabetes-associated pancreatic cancer (PC) and the interaction of diabetes with other risk factors are not well established. We determined the association between diabetes and risk of PC in 2,192 cases and 5,113 controls in three large case–control studies conducted at the National Cancer Institute, the University of California San Francisco, and the M.D. Anderson Cancer Center. In multivariable analyses, diabetes was associated with a 1.8-fold risk of PC [95% confidence interval (CI) = 1.5–2.1]. Risk estimates decreased with increasing years with diabetes (≤2 years OR = 2.9, 95% CI = 2.1–3.9; 3–5 years OR = 1.9, 95% CI = 1.3–2.6; 6–10 years OR = 1.6, 95% CI = 1.2–2.3; 11–15 years OR = 1.3, 95% CI = 0.9–2.0; > 15 years OR = 1.4, 95% CI = 1.0–2.0 (p for trend < 0.0001). Among diabetics, risk was higher in insulin ever users compared with nonusers (OR = 2.2, 95% CI = 1.6–3.7) and was restricted to insulin use of ≤3 years (OR = 2.4). Insulin use of >10 years was associated with a reduced risk of pancreatic cancer (OR = 0.5, 95% CI = 0.3–0.9; p for trend < 0.0001). Hispanic men and Asians had a higher risk of diabetes-associated PC than did whites and blacks, but the differences were not statistically significant. No significant interaction between diabetes and cigarette smoking, alcohol consumption and body mass index was observed. Although reverse causation may explain the association between diabetes diagnosed in close temporal proximity to PC, our results show that long-term diabetes, even though risk diminishes over time, remains a risk factor for PC independent of obesity and smoking.