Breast conserving surgery versus mastectomy: the influence of comorbidities on choice of surgical operation in the Department of Defense health care system.

BACKGROUND: Studies on the effect of comorbidities on breast cancer operation have been limited and inconsistent. This study investigated whether pre-existing comorbidities influenced breast cancer surgical operation in an equal access health care system. METHODS: This study was based on linked Department of Defense cancer registry and medical claims data. The study subjects were patients diagnosed with stage I to III breast cancer during 2001 to 2007. Logistic regression was used to determine if comorbidity was associated with operation type and time between diagnosis and operation. RESULTS: Breast cancer patients with comorbidities were more likely to receive mastectomy (odds ratio [OR] = 1.27; 95% confidence interval [CI], 1.14 to 1.42) than breast conserving surgery plus radiation. Patients with comorbidities were also more likely to delay having operation than those without comorbidities (OR = 1.27; 95% CI, 1.14 to 1.41). CONCLUSIONS: In an equal access health care system, comorbidity was associated with having a mastectomy and with a delay in undergoing operation.

Race and colon cancer survival in an equal-access health care system.

Studies have shown that Whites have a higher colorectal cancer survival rate than Blacks. However, it is unclear whether racial disparities result from unequal access to medical care or factors other than health care access or both. This study assessed whether non-Hispanic Whites (NHW) and non-Hispanic Blacks (NHB) differ in colon cancer survival in an equal-access health care system and examined whether racial differences varied by demographic and tumor characteristics. The study included 2,537 Military Health System patients diagnosed with colon cancer between 1998 and 2007. Median follow-up time was 31.4 months. Cox models estimated HRs and 95% confidence intervals (CI) for race, overall and stratified by age at diagnosis, sex, and tumor stage. No difference in overall survival (OS) between NHWs and NHBs was observed in general. However, among patients younger than 50 years old, NHBs experienced significantly worse OS than NHWs (HR: 2.03, 95% CI: 1.30-3.19). Furthermore, stratification by sex and tumor stage showed that this racial disparity was confined to women (HR: 2.87; 95% CI: 1.35-6.11) and patients with distant stage disease (HR: 2.45; 95% CI: 1.15-5.22) in this age group. When medical care is equally available to NHWs and NHBs, similar overall colon cancer survival was observed; however, evidence of racial differences in survival was apparent for patients younger than 50 years old. This study suggests that factors other than access to care may be related to racial disparities in colon cancer survival among younger, but not older, patients.

Socioeconomic disparities and breast cancer hormone receptor status.

PURPOSE: Recent research, although inconsistent, indicates that socioeconomic status (SES) may be associated with hormone receptor (HR) status. This study aims to examine the association between SES and breast cancer HR status within and across racial/ethnic groups stratified by age at diagnosis and tumor stage. METHODS: The study subjects were 184,602 women with incident breast cancer diagnosed during 2004-2007 and identified from the National Cancer Institute's Surveillance, Epidemiology and End Results program. Log-binomial regression assessed the risk of having breast tumors that were (1) HR-negative versus HR-positive and (2) HR-unknown versus HR-known between women who, at the time of diagnosis, were residing in high or medium poverty areas compared to low poverty areas. RESULTS: High poverty areas tended to have a greater prevalence of HR-negative tumors compared to more affluent areas. Although not always significant, this was observed among non-Hispanic white and Hispanic women regardless of age-tumor stage category, and only among young, non-Hispanic black women and non-Hispanic Asian/Pacific Islander women with regional and distant stage. High poverty areas also tended to have a greater prevalence of HR-unknown tumors compared to more affluent areas. Furthermore, significant trends between HR status and poverty level varied by race/ethnicity, age, and tumor stage. CONCLUSIONS: Poverty may be related to breast cancer negative and unknown HR status. These findings suggest the effects of non-genetic factors on biochemical features of breast cancer, as well as imply a clinical importance to improve HR measurement or recording for low socioeconomic breast cancer patients.

Uterine serous carcinoma: increased familial risk for lynch-associated malignancies.

Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for patients with serous uterine carcinoma, focusing on Lynch syndrome malignancies. Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair (MMR) abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second-stage analysis was undertaken using data from Gynecologic Oncology Group (GOG)-210. Incidence data for cancers reported in relatives of 348 patients with serous and mixed epithelial and 624 patients with endometrioid carcinoma were compared. Nineteen of 29 (65.5%) patients in the single-institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly overrepresented and a high number of probands (6 of 29, 20.7%) reported pancreatic cancers. None of the probands' tumors had DNA MMR abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case-control study. Pancreatic cancers were, however, significantly more common in relatives of patients with serous cancer [OR, 2.39; 95% confidence interval (CI), 1.06-5.38]. We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of patients with serous cancer in a single-institution study. Follow-up studies suggest that only pancreatic cancers are overrepresented in relatives. DNA MMR defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers.

Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort.

There are several biologic mechanisms whereby coffee might reduce breast cancer risk. Caffeine and caffeic acid, major coffee constituents, have been shown to suppress mammary tumor formation in animal models and to inhibit DNA methylation in human breast cancer cells, respectively. Coffee may also reduce risk through decreasing inflammation and influencing estrogen metabolism. However, epidemiologic studies have been inconsistent and few studies have examined the association by estrogen and progesterone receptor (ER/PR) status. We evaluated coffee intake for its effect on incident breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort, which included 198,404 women aged 50-71 with no history of cancer, who in 1995-1996 completed a questionnaire capturing usual coffee intake over the past year. State cancer registry and mortality index linkage identified 9,915 primary incident breast carcinomas through December 2006; available information on hormone receptor (HR) status identified 2,051 ER+/PR+ and 453 ER-/PR- cancers. In multivariable proportional hazards models, coffee intake was not associated with breast cancer risk (p-value for trend = 0.38; relative risk = 0.98, 95% confidence interval: 0.91-1.07, for four or more cups per day as compared to women who never drank coffee), and results did not vary by body mass index or history of benign breast biopsy (p-value for interaction > 0.10). We found no evidence of a relationship with either caffeinated or decaffeinated coffee. Null findings persisted for risk of both HR-positive and -negative breast cancers. These findings from a large prospective cohort do not support a role of coffee intake in breast carcinogenesis.

Reproductive and hormonal factors and lung cancer risk in the NIH-AARP Diet and Health Study cohort.

BACKGROUND: Lung cancer exhibits unique patterns among women including high adenocarcinoma rates among nonsmokers. Inconsistent findings about hormonal factors on risk may reflect incomplete control for confounding, misclassification of exposures, or insufficient attention to variation by histology. METHODS: Among 185,017 women, ages 50 to 71 years, recruited during 1995 and 1996 for the NIH-AARP (American Association of Retired Persons) Diet and Health Study, we identified 3,512 incident lung cancers (including 276 in never smokers) in follow-up through December 2006. Multivariable Cox proportional hazards models estimated relative risks (RR) and 95% CIs for self-reported hormonally related risk factors. RESULTS: After adjustment for smoking and other confounders, subjects with late menarche were at reduced risk, with the association specific for adenocarcinomas (RR = 0.72 for menarche 15+ vs. <11, P(trend) < 0.01). Subjects with early ages at ovarian cessation (either from natural menopause or bilateral oophorectomy) were at an increased risk for adenocarcinomas and squamous cell tumors, but the associations were strongest for smokers, suggesting either residual confounding or an enhanced effect of menopausally related factors among subjects with decreased endogenous estrogens. In contrast, we saw no relationships of risk with either parity, age at first birth, or exogenous hormone use. CONCLUSIONS: Elevated levels of hormones may adversely affect lung function early in life while assisting with cellular and immunologic responses later in life. Additional attention toward the role of hormonal factors may further our understanding of lung carcinogenesis. IMPACT: Our findings provide some support for a role of hormonal factors in the etiology of lung cancer, although the mechanisms appear complicated.

Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: results from a population-based case-control study in Poland.

INTRODUCTION: Studies suggest that high circulating levels of prolactin increase breast cancer risk. It is unclear if genetic variations in prolactin (PRL) or prolactin receptor (PRLR) genes also play a role. Thus, we examined the relationship between single nucleotide polymorphisms (SNPs) in PRL and PRLR, serum prolactin levels and breast cancer risk in a population-based case-control study. METHODS: We genotyped 8 PRL and 20 PRLR tag SNPs in 1965 breast cancer cases and 2229 matched controls, aged 20-74, and living in Warsaw or Lódz, Poland. Serum prolactin levels were measured by immunoassay in a subset of 773 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for genotype associations with breast cancer risk were estimated using unconditional logistic regression, adjusted for age and study site. Geometric mean prolactin levels were estimated using linear regression models adjusted for age, study site, blood collection time, and menstrual cycle day (premenopausal women). RESULTS: Three SNPs were associated with breast cancer risk: in premenopausal women, PRLR rs249537 (T vs. C per-allele OR 1.39, 95% CI 1.07 - 1.80, P = 0.01); and in postmenopausal women, PRLR rs7718468 (C vs. T per-allele OR 1.16, 95% CI 1.03 - 1.30, P = 0.01) and PRLR rs13436213 (A vs. G per-allele OR 1.13 95% CI 1.01 - 1.26, P = 0.04). However, mean serum prolactin levels for these SNPs did not vary by genotype (P-trend > 0.05). Other SNPs were associated with serum prolactin levels: PRLR rs62355518 (P-trend = 0.01), PRLR rs10941235 (P-trend = 0.01), PRLR rs1610218 (P-trend = 0.01), PRLR rs34024951 (P-trend = 0.02), and PRLR rs9292575 (P-trend = 0.03) in premenopausal controls and PRL rs849872 (P-trend = 0.01) in postmenopausal controls. CONCLUSIONS: Our data provide limited support for an association between common variations in PRLR and breast cancer risk. Altered serum prolactin levels were not associated with breast cancer risk-associated variants, suggesting that common genetic variation is not a strong predictor of prolactin-associated breast cancer risk in this population.

Extraneural manifestations of prion infection in GPI-anchorless transgenic mice.

Earlier studies indicated that transgenic (tg) mice engineered to express prion protein (PrP) lacking the glycophosphatidylinositol (GPI⁻/⁻) membrane anchor formed abnormal proteinase-resistant prion (PrPsc) amyloid deposits in their brains and hearts when infected with the RML strain of murine scrapie. In contrast, RML scrapie infection of normal mice with a GPI-anchored PrP did not deposit amyloid with PrPsc in the brain or the heart. Here we report that scrapie-infected GPI⁻/⁻ PrP tg mice also deposit PrP and transmissible infectious material in the gut, kidneys, and islets of Langerhans. Similar to previously reported amyloid deposits in the brain and heart, amyloid deposits were found in the gut; however, no amyloid deposited in the islets. By high-resolution electron microscopy, we show PrP is located primarily in α cells and also ß cells. Islets contain abundant insulin and there is no abnormality in glucose metabolism in infected GPI⁻/⁻ PrP tg mice.

The association between family meals, TV viewing during meals, and fruit, vegetables, soda, and chips intake among Latino children.

OBJECTIVE: Examine the relationship of family meals to children's consumption of fruit and vegetables as well as soda and chips. Additionally, to assess the relationship between viewing TV during family meals and children's diet. DESIGN: Cross-sectional study that used a questionnaire completed by parents. SETTING: Thirteen schools in San Diego, California. PARTICIPANTS: Seven hundred ninety-four children and their parents. ANALYSIS: Ordinal regression assessed associations between children's intake of fruit, vegetables, soda, and chips with family meal frequency and TV viewing during family meals. RESULTS: Children who consumed breakfast, lunch, or dinner with their family at least 4 days per week ate fruit and vegetables 5 or more times a week 84%, 85%, and 80%, respectively. Of those children who ate breakfast, lunch, or dinner with their family at least 4 days per week, 40%, 44%, and 43% consumed soda and chips 5 or more times a week, respectively. Children who ate breakfast with their families at least 4 times a week were more likely to consume fruit and vegetables, and children whose TV was never or rarely on during family meals were less likely to consume soda and chips (P = .04 and P < .001, respectively). CONCLUSIONS: Interventions geared at increasing the frequency of eating breakfast as a family and decreasing the amount of TV watched during family meals are needed, especially among acculturating Latino families.

CD4 T cell control primary measles virus infection of the CNS: regulation is dependent on combined activity with either CD8 T cells or with B cells: CD4, CD8 or B cells alone are ineffective.

Measles virus (MV), one of the most infectious of human pathogens, still infects over 30 million humans and causes over 500,000 deaths each year [Griffin, D., 2001. Measles virus. In: Fields, B., Knipe, D., Howley, P. (Eds.), Fields Virology. Lippincott-Raven, Philadelphia, pp. 1401-1442; ]. Death is primarily due to secondary microbial infections associated with the immunosuppression caused by MV. Studies of humans with genetic or acquired deficiencies of either the humoral or cellular arm of the immune system, and rodent models have implicated T cells in the control of the ongoing MV infection but the precise role and activities of the specific T cell subset or the molecules they produce is not clear. Using a transgenic mouse model in conjunction with depletion and reconstitution of individual B and T cell subsets alone or in combination, we show that neither CD4, CD8 nor B cells per se control acute MV infection. However, combinations of either CD4 T cells and B cells, or of CD4 and CD8 T cells are essential but CD8 T with B cells are ineffective. Interferon-gamma and neutralizing antibodies, but neither perforin nor TNF-alpha alone are associated with clearance of MV infection. TNF-alpha combined with interferon-gamma is more effective in protection than interferon alone. Further, the lack of an interferon-gamma response leads to persistence of MV.