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Background Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. Design Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case–control studies (1983–2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. Results Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69–0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54–0.80) and FL (pooled OR = 0.82, 95% CI 0.66–1.01). Conclusion Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL. [ABSTRACT FROM PUBLISHER]

The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985--1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR)=1.8, 95% confidence interval (CI)=0.6-5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI=0.8-8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population. [ABSTRACT FROM AUTHOR]

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case-control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin. [ABSTRACT FROM AUTHOR]

Tamoxifen prevents recurrence after breast cancer and breast cancer among high-risk women, and may prevent myocardial infarction (MI). To assess the impact of tamoxifen on MI risk, we conducted a case-control study of first MI after breast cancer nested among women diagnosed with breast cancer, while enrolled in a health maintenance organisation from 1980 to 2000. We obtained information on breast cancer treatment and MI risk factors through medical record reviews and interviews. Data were analysed using conditional logistic regression. Of 11,045 women with breast cancer, 134 met MI criteria and were matched to two MI-free control subjects on year of birth and breast cancer diagnosis. After adjusting for smoking, hypertension and diabetes, tamoxifen was unassociated with MI (odds ratio (OR)=1.2, 95% confidence interval (CI)=0.7-1.9). Duration, cumulative dose and recency of use were not associated with MI. Radiation therapy was associated with MI (OR=2.0, 95% CI=1.1-3.5), an association that varied slightly but not statistically significantly by tamoxifen use (radiation with tamoxifen, OR=2.0, 95% CI=0.9-4.4; radiation without tamoxifen, OR=2.9, 95% CI=1.2-7.5). Tamoxifen treatment for breast cancer does not appear to increase or decrease MI risk, although radiation therapy appears to increase MI risk. [ABSTRACT FROM AUTHOR]

We evaluated prediagnosis predictors of breast cancer survival among 717 premenopausal breast cancer patients enrolled in a population-based case-control study and followed for 10.4 years. Using Cox's proportional hazards models, lifetime exercise, weight, and height were not associated with survival. Higher body mass index (trend P=0.21) and recent exercise activity (trend P=0.31) were weakly associated with longer survival. [ABSTRACT FROM AUTHOR]

Recent reports suggest that two ATM gene mutations, 7271T>G and IVS10-6T>G, are associated with a high risk of breast cancer among multiple-case families. To assess the importance of these two mutations in another 'high-risk' group, young women (under age 51) with multiple primaries, we screened a large population-based series of young women with bilateral breast cancer and compared the frequency of these mutations among similar women diagnosed with unilateral breast cancer. The 1149 women included were enrolled in an ongoing population-based case-control study of the genetic factors that contribute to bilateral breast cancer; they were not selected on the basis of family history of cancer. Screening for 7271T>G and IVS10-6T>G ATM gene mutations was conducted using DHPLC followed by direct sequencing. The 7271T>G mutation was detected in one out of 638 (0.2%) women with unilateral breast cancer and in none of the bilateral cases, and the IVS10-6T>G mutation in one out of 511 (0.2%) bilateral and in eight out of 638 (1.3%) unilateral breast cancer cases. Carriers of either mutation were not limited to women with a family history. Given the likelihood that young women with bilateral breast cancer have a genetic predisposition, the observed mutation distribution is contrary to that expected if these two mutations were to play an important role in breast carcinogenesis among individuals at high risk. [ABSTRACT FROM AUTHOR]

Lymphangiosarcoma of the upper extremity is a rare and aggressive tumour reported to occur following post-mastectomy lymphoedema (Stewart-Treves syndrome). Haemangiosarcoma, a related rare tumour, has occasionally been reported to occur in the breast following irradiation. We conducted a case-control study using the University of Southern California-Cancer Surveillance Program, the population-based cancer registry for Los Angeles County, to evaluate the relationship between invasive female breast cancer and subsequent upper extremity or chest lymphangiosarcoma and haemangiosarcoma together referred to as angiosarcoma. Cases were females diagnosed between 1972 and 1995 with angiosarcoma of the upper extremity (n = 20) or chest (n = 48) who were 25 years of age or older and residing in Los Angeles County when diagnosed. Other sarcomas at the same anatomic sites were also studied. Controls were females diagnosed with cancers other than sarcoma during the same time period (n = 266,444). Cases and controls were then compared with respect to history of a prior invasive epithelial breast cancer. A history of breast cancer increased the risk of upper extremity angiosarcoma by more than 59-fold (odds ratio [OR] = 59.3, 95% confidence interval [95% CI] = 21.9-152.8). A strong increase in risk after breast cancer was also observed for angiosarcoma of the chest and breast (OR = 11.6, 95% CI = 4.3-26.1) and for other sarcomas of the chest and breast (OR = 3.3, 95% CI = 1.1-1.7). [ABSTRACT FROM AUTHOR]

Background: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association.Methods: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided.Results: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups.Conclusions: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories. [ABSTRACT FROM AUTHOR]

Lifetime exercise activity has been linked to breast cancer risk among young women. However, no study has specifically evaluated whether lifetime exercise activity is related to the breast cancer risk of post-menopausal women. We conducted a population-based case-control study of post-menopausal white women (1123 newly diagnosed cases and 904 healthy controls) aged 55-64 who lived in Los Angeles County, California, USA to evaluate this relationship. Although neither exercise activity from menarche to age 40 years, nor exercise after age 40 separately predicted breast cancer risk, risk was lower among women who had exercised each week for at least 17.6 MET-hours (metabolic equivalent of energy expenditure multiplied by hours of activity) since menarche than among inactive women (odds ratio (OR) = 0.55; 95% confidence interval (CI) 0.37-0.83). Exercise activity was not protective for women who gained considerable (> 17%) weight during adulthood. However, among women with more stable weight, breast cancer risk was substantially reduced for those who consistently exercised at high levels throughout their lifetime (OR = 0.42; 95% CI 0.24-0.75), those who exercised more than 4 h per week for at least 12 years (OR = 0.59; 95% CI 0.40-0.88), and those who exercised vigorously (24.5 MET-hours per week) during the most recent 10 years (OR = 0.52; 95% CI 0.32-0.85). Strenuous exercise appears to reduce breast cancer risk among post-menopausal women who do not gain sizable amounts of weight during adulthood. [ABSTRACT FROM AUTHOR]

Background: In the United States, Blacks have increasingly higher rates of oral and pharyngeal cancer (oral cancer) than Whites, but determinants of the racial disparity have not been clear.Purpose: The purpose of this study was to explore reasons for the higher incidence of oral cancer among Blacks than Whites.Methods: We used data from a large, population-based case-control study of oral cancer risk factors conducted in four areas of the United States. On the basis of interviews that ascertained characteristics of 1065 oral cancer patients (871 Whites and 194 Blacks) and 1182 controls (979 Whites and 203 Blacks), we examined racial differences in exposure prevalences and relative risks for a number of known etiologic factors, including tobacco and alcohol consumption, diet, and socioeconomic and other variables. To evaluate the extent to which the major risk factors explained the excess risk of oral cancer among Blacks, population-attributable risks were calculated.Results: Differences with respect to alcohol consumption, especially among current smokers, emerged as the most important explanatory variables. After adjusting for smoking, heavy drinking (> or = 30 drinks/week) resulted in a 17-fold increased risk among Blacks and a ninefold increase among Whites. Among drinkers, Blacks tended to drink more than Whites. Also, a higher (P = .01) percentage of Blacks (37%) than Whites (28%) were current smokers, although there were little or no racial differences in relative risks or patterns of use for other smoking variables, including number of cigarettes smoked per day, years of smoking, and age started smoking. From population-attributable risk calculations, we estimated that differences in alcohol and tobacco use account for the bulk of the higher incidence of oral cancer among Blacks in the United States and that, in the absence of alcohol and tobacco, the rates of this cancer according to race (Black, White) and gender would be nearly equal. With regard to other potential etiologic factors, protective effects provided by higher dietary intake of fruits and vitamin C were more pronounced for Whites, while Blacks more often tended to be in sociodemographic and medical or dental health categories associated with increased risk.Conclusions: These analyses provide evidence that various environmental or lifestyle determinants of oral cancer may contribute to the higher oral cancer rates in Blacks than in Whites in the United States, but that patterns and risks associated with alcohol consumption, particularly among current smokers, are the most important contributors to the excess risk in Blacks.Implications: These findings suggest that the key to prevention of oral and pharyngeal cancers among both Blacks and Whites is reduced intake of alcoholic beverages and, because of strong interactive effects, the cessation of smoking. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin.Methods: Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos.Results: Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women.Conclusions: Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive. [ABSTRACT FROM AUTHOR]

Details a study which investigated the association between blood transfusions and the incidence of non-Hodgkin's lymphoma (NHL) in Sweden. Details on the patients studied; Results.

Background: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.Methods: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.Results: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer.Conclusions: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.). [ABSTRACT FROM AUTHOR]

Introduction: Tobacco smoking is consistently inversely associated with Parkinson's disease (PD) in men and women; recently this has been related to reverse causation, prompting questions as to whether similar patterns exist for passive smoke exposure. We used baseline and follow-up data from the California Teachers Study, a prospective cohort of women, to investigate whether timing, location and cumulative measures of intensity and duration of passive smoke exposure are associated with PD risk.Methods: Using a nested case-control approach, we included 224 diagnostically validated cases (158 with no history of personal smoking) and selected 3230 age- and race-matched controls (1973 with no history of personal smoking). We estimated odds ratios(ORs) and 95% confidence intervals(CI) by fitting adjusted multivariable unconditional logistic regression models.Results: Among lifelong non-smokers, passive smoke exposure combined across all settings and accumulated over a lifetime was not associated with PD risk (OR = 1.18, 95% CI 0.60, 2.30). Workplace exposure was also not associated with risk. Household exposure during adulthood but not childhood was inversely associated with PD (OR = 0.59, 95% CI 0.40, 0.87). Exposure to passive smoke in other social settings was positively associated with PD (OR = 1.62, 95% CI 1.11, 2.36). These contradictory results may be attributable to chance due to multiple comparisons in subgroup analyses. No pattern emerged to suggest that increasing years of passive smoke exposure, smokiness of the setting, or combined smokiness by exposure years was associated with lower PD risk.Conclusion: Results do not convincingly support a protective effect of passive smoking in PD. [ABSTRACT FROM AUTHOR]

Background The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. Materials and methods Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case–control studies (1983–2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. Results Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled ORtrend = 0.88, 95% CI 0.81–0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04–1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65–1.16). Conclusions Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall. [ABSTRACT FROM PUBLISHER]