Reproductive factors,hormone use and gastric cancer risk: The Singapore Chinese Health Study

Gastric cancer incidence varies greatly worldwide, but is consistently twice as high in men than in women. The hormone‐related factors hypothesized to be associated with lower risk of gastric cancer in women have not been fully explored in populations with a high background risk of gastric cancer. The Singapore Chinese Health Study (SCHS) is a prospective cohort study in which 34,022 of the participants enrolled between 1993 and 1998 were women between 45 and 74 years of age. Information on reproductive histories, hormone replacement therapy (HRT) and oral contraceptive (OC) use was collected through in‐person interviews at baseline. As of December 31, 2013, 269 incident gastric cancer cases were identified. Multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate gastric cancer risk associations. Older age at natural menopause (≥55 versus <45 years: HR = 0.50, 95% CI: 0.25–0.99), type of menopause (other versus natural: HR = 0.48, 95% CI: 0.27–0.87) and greater years of menstrual cycling (fourth versus first quartile: HR = 0.67, 95% CI: 0.46–0.96) were associated with a decreased risk of gastric cancer. Ever use of OCs and HRT was also associated with reduced risk of gastric cancer; the multivariable‐adjusted HRs (95% CIs) were 0.40 (0.17–0.90) for use of HRT >3 years and 0.67 (0.47–0.94) for ever use of OCs, compared with never use. Reproductive factors associated with a longer window of fertility and the use of exogenous hormones were shown to reduce gastric cancer development in a cohort of Chinese women with a high background risk of gastric cancer.     

Smoking and gastric cancer: systematic review and meta-analysis of cohort studies

OBJECTIVE: We conducted a systematic review of studies addressing the relation between cigarette smoking and gastric cancer to estimate the magnitude of the association for different levels of exposure and cancer locations. METHODS: Published cohort, case-cohort, and nested case-control studies were identified through PubMed, Scopus, and Web of Science searches, from inception to July 2007. Relative risk (RR) estimates referring to the comparison of two categories of exposure (e.g., current smokers vs. never smokers) were combined using a random effects model. Generalized least squares regression was used for trend estimation. Heterogeneity was quantified using the I (2) statistic. RESULTS: Forty-two articles were considered for the systematic review. Comparing current smokers with never smokers: the summary RR estimates were 1.62 in males (95% CI: 1.50-1.75; I (2) = 46.0%; 18 studies) and 1.20 in females (95% CI: 1.01-1.43; I (2) = 49.8%; nine studies); the RR increased from 1.3 for the lowest consumptions to 1.7 for the smoking of approximately 30 cigarettes per day in the trend estimation analysis; smoking was significantly associated with both cardia (RR = 1.87; 95% CI: 1.31-2.67; I (2) = 73.2%; nine studies) and non-cardia (RR = 1.60; 95% CI: 1.41-1.80; I (2) = 18.9%; nine studies) cancers. CONCLUSION: Our study provides solid evidence to classify smoking as the most important behavioral risk factor for gastric cancer.     

Family history of breast cancer as a risk factor for ovarian cancer in a prospective study

BACKGROUND: A family history of breast cancer has been associated with increased ovarian cancer risk. However, few studies have assessed risk according to characteristics that suggest an inherited cancer susceptibility disorder, such as earlier-than-usual age at cancer diagnosis, family members with double primary cancers of different types, multiple relatives with cancer, and cancer in both members of paired organs. METHODS: Ovarian cancer risk was assessed according to a detailed breast cancer family history among 49,975 participants in the Breast Cancer Detection Demonstration Project Breast Cancer Defection Demenstration Project (BCDDP) Follow-up Study (1979-1998). In all, 362 incident ovarian cancers were identified during follow-up and rate ratios (RRs) were calculated by Poisson regression. RESULTS.: Breast cancer in a first- or second-degree relative was associated with increased risk of ovarian cancer (RR = 1.4; 95% confidence interval [CI] = 1.1-1.7). Having 2 or more affected first-degree relatives was associated with increased risk (RR = 1.8; 95% CI = 1.1-2.8), especially for women diagnosed with ovarian cancer before age 60 (RR = 4.2; 95% CI = 1.9-9.2) or with a personal history of breast cancer (RR = 3.7; 95% CI 1.8-7.7). Risk was also particularly high for women with 2 or more first-degree relatives with breast cancer and at least 1 affected relative diagnosed before age 50 (RR = 2.6; 95% CI = 1.4-4.8) or with bilateral breast cancer (RR = 4.2; 95% CI = 1.7-10). CONCLUSIONS: A detailed breast cancer family history as well as an individual's age and personal history of breast cancer are useful for identifying women at elevated genetic risk of ovarian cancer.     

Is family history of breast cancer a marker of susceptibility to exposures in the incidence of de novo adult acute leukemia?

The risk factors for adult acute leukemia incidence have been difficult to establish.Family history of cancer might interact with environmental exposures to produce associations that are otherwise difficult to detect. In addition to family history of leukemia or other hematopoietic cancers, family history of breast cancer could be a marker of susceptibility, because leukemia and breast cancer are known to cluster in families that have specific germ-line mutations. In a population-based case control study of 779 incident adult acute leukemia patients and 625 controls, we estimated the relative risk for exposed individuals with a family history compared with unexposed individuals without a family history (RR(11)), along with a measure of interdependence, the interaction contrast ratio. Combined with a family history of breast cancer, ever-smoking [RR(11) = 2.4, 95% confidence interval (CI): 1.2-4.8], general solvent exposure (RR(11) = 1.9, 95% CI: 1.1-3.4), aromatic hydrocarbon exposure (RR(11) = 3.8, 95% CI: 1.1-14), and diagnostic ionizing radiation exposure (RR(11) = 2.1, 95% CI: 1.2-3.8) were all associated with increased incidence. Furthermore, there was no increased incidence associated with any of these exposures in the absence of a family history of breast cancer and no increased incidence for family history of breast cancer in the absence of exposures. The pattern of relative risks strongly suggested synergy across exposures. Family history of breast cancer might be a marker of susceptibility to a range of leukemia risk factors, whose effects are generally weak or nonexistent when considered alone.     

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study

BackgroundPostmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies.MethodsWe conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence.ResultsAfter 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44–1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12–0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15–0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23–1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen.ConclusionsThe addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.     

Human T-lymphotropic virus type-I infection, survival and cancer risk in southwestern Japan: a prospective cohort study

OBJECTIVES: This study prospectively evaluated the associations of human T-lymphotropic virus type-I (HTLV-I) infection with survival and cancer incidence. METHODS: The study base comprised 4297 adults (aged 40-69 years in 1993) who had either visited the outpatient clinic or who had received annual health check-ups at the A Hospital, Nagasaki, Japan, between 1985 and 1992 (HTLV-I seropositivity = 24.7%). During the follow-up period (1993-1999 or 2000), 290 deaths and 261 cases of malignant neoplasms occurred, including ten deaths and six incident cases of adult T-cell leukemia/lymphoma (ATL). RESULTS: After adjustment for gender, age and other covariates, HTLV-I seropositivity was associated with an increased mortality from all-causes excluding ATL (rate ratio, RR = 1.3, 95% confidence interval, CI = 1.0-1.7), all non-neoplastic diseases (RR = 1.5, 95% CI = 1.0-2.3) and heart diseases. HTLV-I infection was not found to be associated with an increased risk of developing total cancers other than ATL (RR = 0.98, 95% CI = 0.74-1.3), colorectal cancers, liver cancer or lung cancer, but was associated with a reduced risk of gastric cancer (RR = 0.42, 95% CI = 0.17-0.99). CONCLUSIONS: HTLV-I infection is associated with increased mortality from all-causes excluding ATL and all non-neoplastic diseases. HTLV-I carriers may not be at increased general cancer risk, but at reduced risk of gastric cancer.     

Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh-day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow-up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12-2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00-1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71-2.85).     

Increased incidence of small and well-differentiated breast tumours in post-menopausal women following hormone-replacement therapy

Exposure to hormone-replacement therapy (HRT) has consistently been associated with an increased incidence of breast cancer, particularly of small tumours. Other tumour characteristics in relation to HRT have received less scientific attention. Our aim in this population-based prospective cohort study was to assess whether HRT is associated with an increased incidence of breast-cancer subgroups defined in terms of stage, type (according to the WHO system), Nottingham grade and the Nottingham Prognostic Index (NPI). Evaluation was based on a cohort of 5,865 post-menopausal women followed for an average of 9.8 years. Twenty percent of women reported current use of HRT at the time of the baseline interview. Record linkage with the Swedish Cancer Registry and local clinical registries identified 141 incident invasive breast-cancer cases. All tumours were reclassified by 1 pathologist. The incidence of breast cancer in HRT users was 377/10(5) and in non-users 221/10(5) person-years [relative risk (RR) = 1.72, 95% confidence interval (CI) 1.17-2.52]. This risk remained statistically significant after adjustment for established risk factors in a Cox proportional hazards analysis (RR = 1.66, 95% CI 1.12-2.45). Among HRT users, there was over-representation of cases with stage I tumours (adjusted RR = 2.33, 95% CI 1.44-3.76), of lobular carcinomas (RR = 4.38, 95% CI 1.60-12.0) and of tubular tumours (RR = 4.81, 95% CI 1.37-16.8). Nottingham grade I/II carcinomas (RR = 2.02, 95% CI 1.29-3.16) and cases with NPI < or = 3.4 (RR = 2.29, 95% CI 1.41-3.72) were similarly over-represented among HRT users. Incidence of breast cancer was increased in post-menopausal women who used HRT at baseline. Among HRT users, there was over-representation of tumours that, with regard to stage, type and grade, are associated with a favourable prognosis.     

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow-up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT. In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56-6.75, and RR = 1.94, 95% CI = 1.26-3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.     

Patterns of alcohol consumption and breast cancer risk in the California Teachers Study cohort.

Alcohol consumption of approximately two drinks or more per day has been associated with elevated breast cancer risk in the California Teachers Study cohort as well as in many other populations. The objective of this analysis is to examine effects of age at drinking and drinking patterns and to identify effect modifiers. Of the 103,460 at-risk cohort members, age <85, who resided in California and completed the baseline alcohol assessment, 1,742 were diagnosed with invasive breast cancer after joining the cohort and before January 2001. Incident breast cancers were identified through the California Cancer Registry and follow-up for death and confirmation of continued California residence used various sources. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RRs). Elevated breast cancer risk was most evident for recent drinking [RR = 1.28, 95% confidence interval (CI): 1.06-1.54 for >/=20 g/day versus nondrinkers], with no clear pattern for consumption during earlier periods of life. This elevation in risk was 32% among postmenopausal women (95% CI: 1.06-1.63) and 21% among pre/perimenopausal women (95% CI: 0.76-1.92). Highest risks associated with heavy alcohol consumption were observed among postmenopausal women with a history of biopsy-diagnosed benign breast disease (RR = 1.97, 95% CI: 1.39-2.79 compared to nondrinkers without benign breast disease) or who had used combination hormone replacement therapy (HRT) (RR = 2.24, 95% CI: 1.59-3.14 compared to nondrinkers who never used HRT). Recent alcohol consumption equivalent to two or more drinks per day increases the risk of invasive breast cancer, with the greatest RRs observed among heavy drinkers who are also postmenopausal and have a history of benign breast disease or who use HRT.     

Gastric cancer screening and subsequent risk of gastric cancer: a large-scale population-based cohort study, with a 13-year follow-up in Japan

We prospectively investigated the association between gastric cancer screening and subsequent risk of gastric cancer in a large-scale population-based prospective cohort study, with a 13-year follow-up in Japan. Data were analyzed from a population-based cohort of 42,150 (20,326 men and 21,824 women) subjects. Approximately 36% of subjects reported that they had undergone screening photofluorography during the preceding 12 months, and were regarded as the screened group. A total of 179 gastric cancer deaths and 636 incident gastric cancers were identified during the follow-up period. We observed a 2-fold decrease in gastric cancer mortality in screened versus unscreened subjects (RR = 0.52; 95% CI = 0.36-0.74). The extent of the reduction in mortality for gastric cancer was greater than in death from all causes excluding gastric cancer (RR = 0.71; 95% CI = 0.65-0.78). A significant decrease in the incidence of advanced gastric cancer was observed in screened subjects (RR = 0.75; 95% CI = 0.58-0.96), although the overall incidence rate did not differ significantly between the screened and unscreened subjects (RR = 1.06; 95% CI = 0.90-1.25). In age-stratified analyses, a significant reduction in gastric cancer mortality was seen in screened subjects aged 40-49 years at baseline, compared with a lesser reduction in screened subjects aged 50-59 (RR = 0.30, 95% CI = 0.13-0.72; and RR = 0.60, 95% CI = 0.40-0.88, respectively). These findings suggest that gastric cancer screening may be associated with a reduced risk of mortality from gastric cancer.     

Physical activity in relation to total, advanced, and fatal prostate cancer

Physical activity has been inconsistently related to total prostate cancer and few studies have examined whether this association varies by disease aggressiveness. We examined physical activity in relation to total, advanced, and fatal prostate cancer in the NIH-AARP Diet and Health Study. At baseline (1995-1996), 293,902 men ages 50 to 71 years completed a questionnaire inquiring about current frequency of vigorous exercise of at least 20 min of duration, as well as frequency of exercise during adolescence (ages 15-18). We used proportional hazards regression to calculate multivariate relative risks (RR) and 95% confidence intervals (95% CI). During up to 8.2 years of follow-up, 17,872 prostate cancer cases were identified, including 1,942 advanced and 513 fatal cases. Comparing frequent (5+ times per week) versus infrequent (less than once per week) vigorous exercise, exercise at baseline was not associated with risk of total prostate cancer (RR, 1.01; 95% CI, 0.96-1.07; P(trend) = 0.78), advanced prostate cancer (RR, 1.14; 95% CI, 0.97-1.33; P(trend) = 0.25), or fatal prostate cancer (RR, 0.90; 95% CI, 0.67-1.20; P(trend) = 0.12). Increasing level of vigorous exercise during adolescence was associated with a small 3% reduction in total prostate cancer risk (frequent versus infrequent exercise during adolescence: RR, 0.97; 95% CI, 0.91-1.03; P(trend) = 0.03) but was not associated with risk of advanced prostate cancer (RR, 0.95; 95% CI, 0.78-1.14; P(trend) = 0.18) or fatal prostate cancer (RR, 0.96; 95% CI, 0.67-1.36; P(trend) = 0.99). Neither vigorous exercise at baseline nor exercise during adolescence was related to risk of total, advanced, or fatal prostate cancer in this large prospective cohort.     

Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer

BACKGROUND: Smoking, caffeine, and alcohol intake are all potentially modifiable factors that have an unclear association with ovarian cancer risk. Therefore, the associations between these exposures and ovarian cancer risk were prospectively examined among 110,454 women in the Nurses' Health Study (NHS) for the smoking analyses and 80,253 women for the dietary analyses. METHODS: Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976, with food frequency questionnaires administered every 2 to 4 years starting in 1980. For the smoking analyses, 737 confirmed cases of epithelial ovarian cancer were identified and for the dietary aims, 507 cases were identified through June 1, 2004. RESULTS: Compared with never-smokers, neither current nor past smoking was associated with ovarian cancer risk overall; however, both were associated with mucinous tumors (n = 69; rate ratio [RR], past = 2.02 [95% confidence interval (CI), 1.15-3.55]; RR, current = 2.22 [95% CI, 1.16-4.24]). A modest inverse association between caffeine intake and ovarian cancer risk was observed (RR, top vs bottom quintile = 0.80; 95% CI, 0.60-1.07 [P = .03]), which was strongest for women who had never used either oral contraceptives (RR = 0.65; 95% CI, 0.46-0.92 [P for heterogeneity = .02]) or postmenopausal hormones (RR = 0.57; 95% CI, 0.36-0.91 [P for heterogeneity = .13]). Alcohol was not associated with ovarian cancer risk. CONCLUSIONS: The results of the current study suggest that cigarette smoking may only increase the risk for mucinous ovarian tumors, and alcohol intake was not associated with risk. However, an inverse association was observed between caffeine intake and ovarian cancer risk, particularly in women not using hormones; this finding merits further study.     

Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study

PURPOSE: To study the potential risk factors, including radiotherapy (RT) for contralateral breast cancer (CBC), in patients treated for early-stage breast cancer. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database (1973-1996) was used to study the incidence of CBC after breast cancer. The Cox proportional hazards regression model was used to estimate the relative risk (RR) of CBC, with adjustment for confounders, including age, race, histologic subtype, and use of RT. Information on the use of hormonal therapy and chemotherapy was not available in the Surveillance, Epidemiology, and End Results database. RESULTS: A CBC was documented in 5679 (4.2%) of the 134501 localized invasive or intraductal breast cancer patients surviving at least 3 months. The 10- and 20-year actuarial rate of CBC was 6.1% and 12%, respectively. In multivariate analysis, medullary carcinoma (RR = 1.18, 95% confidence interval [CI] 1.02-1.37), black race (RR = 1.20, 95% CI 1.08-1.33), and age >55 years at initial diagnosis (RR = 1.15, 95% CI 1.08-1.22) were associated with increased CBC risk. A total of 1234 (3.3%) of 37,379 patients who received RT developed CBC, and 4445 (4.6%) of 97122 patients who did not receive RT developed CBC. Overall, RT was not associated with an increased risk of CBC (RR = 1.04, 95% CI 0.97-1.10) in multivariate analysis. The CBC risk associated with RT varied substantially with the length of follow-up. During the first 5 years of follow-up, RT was not associated with an increased CBC risk (age-adjusted RR = 0.96, 95% CI 0.88-1.04). For patients surviving for >5 years, RT was associated with a 14% increase in CBC risk (RR = 1.14, 95% CI 1.03-1.26). The increased CBC risk with RT was evident in patients aged <45 years (RR = 1.32, p = 0.01) and >55 years (RR = 1.15, p = 0.04) at initial diagnosis. The 5-, 10-, 15-, and 20-year actuarial rate of CBC was 2.9%, 6.5%, 10.2%, and 13.4%, respectively, for patients with RT; the corresponding rates were 3.0%, 6.0%, 8.9%, and 11.8% for patients without RT. The absolute increase in CBC risk associated with RT was 0.5%, 1.3%, and 1.6% in the 10-, 15-, and 20-year actuarial rate, respectively. CONCLUSION: CBC is not uncommon after breast cancer, especially for certain subsets of patients. RT was associated with a very small increased long-term CBC risk. This minimal increase in CBC risk should not affect clinical decision-making in treatment selection for patients with localized invasive breast cancer or ductal carcinoma in situ. Unnecessary radiation exposure to the contralateral breast should be avoided for all patients with early-stage breast cancer.     

Hormone replacement therapy is not associated with an increased risk of leukemia (United States)

Objective Recent studies have reported an increased risk of certain cancers associated with hormone replacement therapy (HRT), possibly due to stimulation of estrogen receptors. Since estrogen receptors are expressed on certain hematopoietic cells, it is possible that HRT use may also increase the risk of leukemia.Methods A cohort of 37,172 post-menopausal Iowa women ages 55–69 years with no history of prior cancer was linked annually to the population-based state cancer registry through 2001. In addition to other self-reported cancer risk factors, participants were asked about current and former use of HRT in 1986 and on four subsequent follow-up questionnaires. A total of 201 cases of leukemia were identified over 16 years of follow-up including 74 acute myeloid leukemias (AMLs) and 87 chronic lymphocytic leukemias (CLLs).Results Compared to never users of HRT at study baseline, current [multivariate relative risk (RR), 1.09; 95% confidence interval (CI) 0.70–1.71)] and former users (RR=0.82, 95% CI=0.59–1.15) were at no increased risk of developing leukemia. For AML, current users also had no increased risk (RR=0.83, 95% CI=0.37–1.84) and there was a suggestion that former users had a slightly decreased risk (RR=0.66, 95% CI=0.37–1.17). For CLL, all RRs were around unity.Conclusion We conclude that HRT is unlikely to be an appreciable risk factor for leukemia.     

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.     

The Copenhagen case-control study of renal pelvis and ureter cancer: role of smoking and occupational exposures

Smoking habits and occupational exposures were investigated for 96 patients with cancer of the renal pelvis and ureter (including papilloma) and 294 hospital controls. In comparison with persons who never smoked, significantly increased relative risks were seen for smokers of cigarettes alone (RR = 2.6; 95% CI: 1.0-6.7) and in combination with other types of tobacco (RR = 3.8; 95% CI: 1.3-11.5). Non-significantly increased relative risks were observed for pipe smokers (RR = 2.2; 95% CI: 0.1-97) and for mixed pipe, cigar, and cigarillo smokers (RR = 6.5; 95% CI: 0.4-21.2). A strong dose-effect (p less than 0.001) relationship was seen between the lifetime total amount of tobacco smoked and the risk of pelvis-ureter tumors, with the heaviest smokers having an 8-fold risk. Comparison with the dose-effect relationship for a parallel study of bladder cancer indicated that the relationship with tobacco was stronger for pelvis-ureter tumors. Deep inhalation of cigarette smoke increased the risk (RR = 3.4; 95% CI: 1.9-6.1), while stopping smoking (RR = 0.6; 95% CI: 0.3-1.1) and use of filter cigarettes (RR = 0.5; 95% CI: 0.3-0.9) decreased the risk. Significantly increased risks emerged for employment in the chemical, petrochemical and plastics industries (RR = 4.0; 95% CI: 1.6-9.8), and for exposure to coal and coke (RR = 4.0; 95% CI: 1.2-13.6), asphalt and tar (RR = 5.5; 95% CI: 1.6-19.6). Cigarette smoking accounted for 56% of male and 40% of female pelvis and ureter tumors in eastern Denmark.     

Reproductive factors and pancreatic cancer risk: a Norwegian cohort study

A cohort of 63,090 Norwegian women born 1886-1928 was followed more than 38 years, and relations between reproductive factors and risk of pancreatic cancer were explored; 449 cases were recorded at ages 50-89 years. Age at menopause showed a moderately positive association with risk (rate ratio (RR)=1.08 per 2 years delay in menopause; 95% confidence interval (CI)=1.00-1.17). Neither parity nor duration of breastfeeding showed significant associations with risk after adjusting only for demographic factors. With mutual adjustment, however, parity became positively associated (RR=1.13 per delivery; 95% CI=1.05-1.22) while duration of breastfeeding was inversely associated (RR=0.87 per 12 months; 95% CI=0.78-0.97). These associations lessened in magnitude with increasing age, and were essentially absent above age 80 years. Risk was raised among women reporting at least one abortion, but no trend was seen with number of abortions. Together with previous studies, the findings raise questions about the role of chance, but do not exclude hormonal factors related to breastfeeding and pregnancy from affecting pancreatic cancer risk.     

Cigarette smoking,use of other tobacco products and stomach cancer mortality in US adults: The Cancer Prevention Study II

Cigarette smoking is associated with increased risk of stomach cancer in many studies but there are limited data on this relationship in women and on risk associated with use of tobacco products other than cigarettes. We examined stomach cancer death rates in relation to cigarette smoking in women and use of cigarette, cigar, pipe, or smokeless tobacco in men in a nationwide prospective mortality study in the United States (US). Cohort follow-up from 1982-96 identified 996 and 509 stomach cancer deaths among 467,788 men and 588,053 women, respectively. Cox proportional hazards models were fitted to estimate rate ratios (RR) and 95% confidence intervals (CI) using non-users of tobacco as the referent group. Multivariate-adjusted RRs were the highest for men who currently smoked cigars (RR = 2.29, 95% CI = 1.49-3.51) or cigarettes (RR = 2.16, 95% CI = 1.75-2.67) and both increased with smoking duration. Women who currently (RR = 1.49, 95% CI = 1.18-1.88) or formerly (RR = 1.36, 95% CI = 1.08-1.71) smoked cigarettes were at significantly increased risk, as were men who formerly smoked cigarettes (RR = 1.55, 95% CI = 1.28-1.88), or currently (RR = 1.81, 95% CI = 1.40-2.35) or formerly (RR: 1.57, 95% CI = 1.22-2.03) used more than one type of tobacco. Men who reported a history of chronic indigestion or gastroduodenal ulcer had substantially higher mortality rates associated with current cigarette (RR = 3.45, 95% CI = 2.05-5.80) or cigar (RR = 8.93, 95% CI = 4.02-19.90) smoking, as did men who were current aspirin users. If causal, the estimated proportion of stomach cancer deaths attributable to tobacco use would be 28% in US men and 14% in women. We conclude that prolonged use of tobacco products is associated with increased stomach cancer mortality in men and women. The accumulated evidence from this and other studies support reconsidering stomach cancer as a tobacco-related cancer.     

Hormone replacement therapy and risk of non-hodgkin lymphoma and chronic lymphocytic leukemia.

Our objective in this study was to evaluate whether the use of hormone replacement therapy (HRT) is associated with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). A cohort of 37,220 Iowa women ages 55 to 69 years in 1986 with no history of prior cancer was linked annually to a population-based cancer registry. Through 1998 (13 years of follow-up), 258 incident cases of NHL were identified, including 135 cases of diffuse NHL, 58 cases of follicular NHL, and 31 cases of small lymphocytic NHL. In addition, 63 cases of CLL were identified. Current and former use of HRT (primarily estrogen) and other cancer risk factors were self-reported on the baseline (1986) questionnaire. Compared with never users of HRT at study baseline, current [multivariate relative risk (RR), 1.4; 95% confidence intervals (CIs), 0.9-2.0) but not former (RR, 1.1; 95% CI, 0.8-1.4) users were at increased risk of NHL after adjustment for age and other confounding factors. This association was seen only in nodal NHL [RR(current), 1.5 (95% CI, 1.0-2.4); RR(former), 1.1 (95% CI, 0.8-1.6)] and was not apparent for extra-nodal sites. Of the common subtypes, there was a strong positive association with follicular NHL [RR(current), 3.3 (95% CI, 1.6-6.9); RR(former), 2.6 (95% CI, 1.4-4.7)], and women who were current users for more than 5 years had the highest risk (RR, 3.9; 95% CI, 1.8-8.6). There was no association with diffuse or small lymphocytic NHL, or with CLL. Most of the follicular NHLs were nodal (88%), and exclusion of extra-nodal sites slightly strengthened the association with HRT. For diffuse NHL, 64% of the cases were nodal, and there was no association of HRT with either nodal or extra-nodal sites. These data suggest that HRT is a risk factor for follicular NHL but not for diffuse or small lymphocyte NHL or CLL.