Passive smoking exposure and female breast cancer mortality

BACKGROUND: Several studies have reported positive associations between environmental tobacco smoke (ETS) and increased risk of breast cancer. However, studies of active smoking and risk of breast cancer are equivocal and in general do not support a positive association. To try to resolve this paradox, we examined the association between breast cancer mortality and potential ETS exposure from spousal smoking in an American Cancer Society prospective study of U.S. adult women. METHODS: We assessed breast cancer death rates in a cohort of 146 488 never-smoking, single-marriage women who were cancer free at enrollment in 1982. Breast cancer death rates among women whose husbands smoked were compared with those among women married to men who had never smoked. Cox proportional hazards modeling was used to control for potential risk factors other than ETS exposure. RESULTS: After 12 years of follow-up, 669 cases of fatal breast cancer were observed in the cohort. Overall, we saw no association between exposure to ETS and death from breast cancer (rate ratio [RR] = 1.0; 95% confidence interval [CI] = 0.8-1.2). We did, however, find a small, not statistically significant increased risk of breast cancer mortality among women who were married before age 20 years to smokers (RR = 1. 2; 95% CI = 0.8-1.8). CONCLUSIONS: In contrast to the results of previous studies, this study found no association between exposure to ETS and female breast cancer mortality. The results of our study are particularly compelling because of its prospective design as compared with most earlier studies, the relatively large number of exposed women with breast cancer deaths, and the reporting of exposure by the spouse rather than by proxy.     

Exposure to environmental tobacco smoke and risk of lung cancer in non-smoking women from Moscow,Russia

The association between exposure to ETS and the risk of lung cancer in life-time non-smoking women was investigated by means of a hospital based case-control study in Moscow, Russia. The main importance of our study is that it was conducted on a population with a specific smoking pattern from which no information is available on health effects of ETS. A total of 189 incident cases of histologically confirmed lung cancer were identified in 2 principal cancer treatment hospitals in Moscow. A total of 358 female oncology patients from the same hospitals were selected as controls. The controls matched by the hospitals to the cases were similarly restricted to never-smokers. Women diagnosed with cancer of the upper respiratory organs were ineligible for selection as controls. Personal interviews of cases and controls were conducted in the hospital wards, using a closed-form structured questionnaire. An elevated risk of lung cancer was observed in women whose husbands smoked. The odds ratio (OR) adjusted by age and education for husband's smoking was 1.53 (95% CI, 1.06–2.21). Smoking by other members of the family, by colleague's, or by fathers in the women's childhood do not affect the risk of lung cancer. The risk is higher for women whose husbands smoke “papirosy” (OR 2.12; 95% CI, 1.32–3.40), a special Russian type of cigarettes with a long mouthpiece, and usually very high levels of tar (>30 mg/cig) and nicotine (>1.8 mg/cig). Our study suggests that the association between exposure to ETS of the spouse and risk of lung cancer in non-smoking women is somewhat stronger for squamous-cell carcinoma (OR, 1.94; 95% CI, 0.99–3.81) than for adenocarcinoma (OR, 1.52; 95% CI, 0.96–2.39). Int. J. Cancer 75:335–338, 1998. © 1998 Wiley-Liss, Inc.     

Metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke

BACKGROUND: Environmental tobacco smoke (ETS) is associated with lung cancer in nonsmokers. Most epidemiologic studies find a higher risk for lung cancer in nonsmoking women married to smokers than in those married to nonsmokers. We measured metabolites of a tobacco-specific lung carcinogen in urine from healthy, nonsmoking women exposed to ETS. METHODS: We recruited women and their partners through advertisements. Couples completed questionnaires on smoking history and demographics, and both partners provided 100 mL of urine; 23 women had male partners who smoked in the home (i.e., exposed women), and 22 women had male partners who did not smoke (i.e., unexposed women). Urine samples were analyzed for nicotine, for cotinine, for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc), as well as for creatinine. NNAL and NNAL-Gluc are metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Unpaired Student's t tests were conducted on log-transformed values. All statistical tests are two-sided. RESULTS: Urinary levels of nicotine, cotinine, NNAL, and NNAL-Gluc were statistically significantly higher in exposed women than in unexposed women. Geometric means for these compounds in exposed versus unexposed women, respectively, were as follows: nicotine, 0.050 nmol/mg of creatinine (95% confidence interval [CI] = 0.033 to 0.076) versus 0.008 nmol/mg of creatinine (95% CI = 0.004 to 0.014); cotinine, 0.037 nmol/mg of creatinine (95% CI = 0.022 to 0.061) versus 0.007 nmol/mg of creatinine (95% CI = 0.004 to 0.011); NNAL, 0.013 pmol/mg of creatinine (95% CI = 0.007 to 0.024) versus 0.004 pmol/mg of creatinine (95% CI = 0.002 to 0.007); and NNAL-Gluc, 0.027 pmol/mg of creatinine (95% CI = 0.016 to 0.045) versus 0.004 pmol/mg of creatinine (95% CI = 0.003 to 0.006). CONCLUSIONS: Nonsmoking women exposed to ETS take up and metabolize the tobacco-specific lung carcinogen NNK, which could increase their risk of lung cancer. Within couples, the NNAL plus NNAL-Gluc level in exposed women compared with that of their smoking partners averaged 5.6%. Notably, epidemiologic studies have estimated the excess risk for lung cancer in nonsmoking women exposed to ETS as 1%-2% of that in smokers.     

A prospective study of cigarette tar yield and lung cancer

We examined the relationship of cigarette tar yield and other cigarette-usage characteristics in current smokers to the incidence of lung cancer in a study population of 79,946 Kaiser Permanente Medical Care Program members, aged 30–89 years, who completed a detailed, self-administered, smoking-habit questionnaire during the years 1979 through 1985. Mean length of follow-up was 5.6 years. There were 302 incident lung cancers, of which 89 percent occurred in current or former smokers. The tar yield of the current cigarette brand was unassociated with lung cancer incidence (relative risk [RR]=1.02 per 1 mg tar-yield in men, 95 percent confidence interval [CI]=0.98–1.05; RR=0.99, CI=0.96–1.03 in women). However, in long-term (>20 years) smokers, the risk of lung cancer was decreased in women who had smoked filtered cigarettes for 20 or more years relative to lifelong smokers of unfiltered cigarettes (RR=0.36, CI=0.18–0.75), but not in men who had smoked filtered cigarettes for 20 or more years (RR=1.04, CI=0.58–1.87).Authors are with the Division of Research, Kaiser Permanente Medical Care Program, 3451 Piedmont Avenue, Oakland, CA 94611, USA. Address correspondence to Dr Sidney. This study was funded by grants R01 CA 36074 and R35 CA 49761 from the US National Cancer Institute.     

A case–control study of lung cancer and environmental tobacco smoke among nonsmoking women living in Shanghai, China

Introduction: The incidence of lung cancer in women living in China is among the highest in the world but it does not appear that tobacco smoking is a major risk factor for lung cancer. As tobacco smoking is highly prevalent in Chinese men, exposure to environmental tobacco smoke (ETS) may play an important role in the development of lung cancer in Chinese women who never smoked. We conducted the present investigation because previous studies did not account for dietary habits or indoor air pollution from Chinese-style cooking and they did not assess the effect of occupational exposure to ETS.Methods: A population-based, case–control study was conducted to evaluate the relationship between lung cancer and exposure to ETS among nonsmoking women living in Shanghai, China. Five-hundred and four women diagnosed with incident, primary lung cancer between February 1992 and January 1994 were identified through the population-based Shanghai Cancer Registry. A control group of 601 nonsmoking women was selected randomly from the Shanghai Residential Registry, and was approximately frequency-matched to the age distribution of the lung cancer cases. Information on lifetime domestic and occupational exposure to ETS was obtained through face-to-face interviews. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression.Results: The OR for ever exposed to ETS from spouses was 1.1 (95% CI: 0.8–1.5), and the OR for ever exposed to ETS at work was 1.7 (95% CI: 1.3–2.3). Furthermore, the OR increased with increasing number of hours of daily exposure to ETS in the workplace and with increasing number of smoking co-workers. No associations were found for exposure to ETS during childhood.Conclusions: The main findings of the present study are that long-term occupational exposure to ETS, both alone or in combination with exposures at home, conferred an increased risk of lung cancer among women who never smoked. The inconsistency of the results regarding exposure to ETS at home and at work may have been due to lower exposures at home.     

Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population. METHODS: Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS (and other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke. RESULTS: When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P =. 02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year = ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure. CONCLUSIONS: A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele).     

Spontaneous abortion and risk of fatal breast cancer in a prospective cohort of United States women

Controversy exists over the possible relationship between induced and spontaneous abortion and risk of breast cancer. Thus, the association of fatal breast cancer and spontaneous abortion was examined in a large prospective study of United States adult women. After seven years of follow-up, 1,247 cases of fatal breast cancer were observed among 579,274 women who were cancer-free at interview in 1982 and who provided complete reproductive histories. Results from Cox proportional hazards models, adjusted for other risk factors, showed no association between a history of spontaneous abortion and risk of fatal breast cancer (rate ratio [RR]=0.89, 95 percent confidence interval [CI]=0.78–1.02). The RR did not increase with increasing numbers of abortions. Parous women who had a spontaneous abortion before their first term birth were not at increased risk compared with parous women with no history of spontaneous abortion (RR=0.76, CI=0.54–1.05). Women whose only pregnancy ended in a spontaneous abortion were not at increased risk compared with women who were never pregnant (RR=0.61, CI=0.27–1.38) or whose only pregnancy ended in a livebirth (RR=0.72, CI=0.32–1.65). These findings do not support an association between spontaneous abortion and fatal breast cancer.     

Low-Dose Computed Tomography (LDCT) Lung Cancer Screening in Asian Female Never-Smokers Is as Efficacious in Detecting Lung Cancer as in Asian Male Ever-Smokers: A Systematic Review and Meta-Analysis

IntroductionLung cancer in never-smokers is the major cancer cause of death globally. We compared the efficacy of low-dose computed tomography (LDCT) lung cancer screening among never-smokers versus ever-smokers using systematic review and meta-analysis.MethodsLDCT lung cancer screening studies that simultaneously included both ever-smoker and never-smoker participants published by April 30, 2021, were searched through PubMed and Scopus. Primary outcome measure was relative risk (RR) of lung cancer diagnosed among never-smokers versus ever-smokers.ResultsA total of 14 studies (13 from Asia) were included (141,396 ever-smokers, 109,251 never-smokers, 1961 lung cancer cases diagnosed). RR of lung cancer diagnosed between ever-smokers versus never-smokers overall was 1.21 (95% confidence interval [CI]: 0.89–1.65), 1.37 (95% CI: 1.08–1.75) among males, and 0.88 (95% CI: 0.59–1.31) among females. RR was 1.78 (95% CI: 1.41–2.24) and 1.22 (95% CI: 0.89–1.68) for Asian female never-smokers versus male never-smokers and versus male ever-smokers, respectively, and 0.99 (95% CI: 0.65–1.50) versus high-risk ever-smokers (≥30 pack-years). Proportional meta-analysis revealed significantly more lung cancers diagnosed at first scan (95.4% [95% CI: 84.9–100.0] versus 70.9% [95% CI: 54.6–84.9], p = 0.010) and at stage 1 (88.5% [95% CI: 79.3–95.4] versus 79.7% [95% CI: 71.1–87.4], p = 0.071) among never-smokers versus ever-smokers, respectively. RR of lung cancer death and 5-year all-cause mortality in never-smokers versus ever-smokers was 0.27 (95% CI: 0.1–0.55, p < 0.001) and 0.13 (95% CI: 0.05–0.33, p < 0.001), respectively.ConclusionsThe RR of lung cancer detected by LDCT screening among female never-smokers and male ever-smokers in Asia was statistically similar. Overall and lung cancer specific mortality from the lung cancer diagnosed from LDCT screening was significantly reduced among never-smokers compared to ever-smokers.     

Dietary factors and risk of lung cancer in never-smokers

We studied dietary risk factors for lung cancer among never-smokers in a population-based case–control study in Stockholm, 1989–1995. Study subjects were older than 30 years of age and had never smoked regularly. A total of 124 cases (35 men, 89 women) and 235 controls (72 men, 163 women) participated. Exposure information was obtained at interview with study subjects. The never-smoking status was validated by interviews with next-of-kin. A protective effect was suggested for vegetables, mediated primarily by carrots (relative risk [RR], 0.7; 95% confidence interval [CI], 0.4–1.3, and 0.6, 0.3–1.1 for intermediate and high consumption of carrots, respectively). Non-citrus fruits appeared to lower the risk as well, with RR 0.6, 95% CI 0.3–1.3 and 0.5, 0.3–1.0 for intermediate and high consumption, respectively. A protective effect with dose-response was also seen for intake of beta-carotene and total carotenoids. Increased risks were seen for cultured milk products in both genders (RR 2.0, 95% CI 1.1–3.9 for intermediate and 1.6, 0.9–2.9 for high consumption), but for milk only among male high consumers. Our results support evidence linking a diet rich in vegetables and non-citrus fruit with decreased lung cancer risk and suggests that among vegetables, carrot consumption is the most important component or marker for this effect in Sweden. The results regarding milk products could be consistent with dietary fat as a risk factor for lung cancer, although a more comprehensive assessment of fat intake is necessary to explore this relation. Int. J. Cancer 78:430–436, 1998. © 1998 Wiley-Liss, Inc.     

Risk factors for lung cancer among Canadian women who have never smoked

Risk factors for lung cancer among women who had never smoked were assessed in a case-control study of 161 newly diagnosed histologically confirmed cases and 483 population controls between 1994 and 1997 in eight Canadian provinces. Measurement included socio-economic status, smoking habits, alcohol use, diet, residential and occupational histories and exposure to environmental tobacco smoke (ETS). Dose-response associations were observed for consumption of tea, adjusted odds ratios (ORs) 0.6 (95% confidence interval (CI) = 0.3-0.9) for 1-7 cups per week and 0.4 (95% CI = 0.2-0.7) for > or = 8 cups per week (P = 0.0008), and smoked meat, adjusted ORs 1.3 (95% CI = 0.8-2.3) for 0.5 slice per week and 2.1 (95% CI = 1.1-4.0) for >0.5 slice per week (P = 0.02). Regular use of shortening in cooking was also related to lung cancer. Increased ORs with borderline significance were found for total consumption of meat, eggs or French fries and fried potatoes. Passive exposure to ETS at home (or at work) may be associated with lung cancer risk among never-smoker women; the adjusted ORs were 0.7 (95% CI = 0.2-2.3), 1.2 (95% CI = 0.4-3.2), 1.5 (95% CI = 0.5-4.0) for 1-16, 17-30, and 31 or more years of combined residential and/or occupational ETS exposure, respectively, with a similar pattern for smoker-years of ETS exposure.     

Cancer incidence among spouses of patients with colorectal cancer

The risk of colorectal cancer was examined among spouses of approximately 10,000 colorectal cancer patients. A total of 8,095 spouses were identified, and cancer cases in this cohort were sought in the Danish Cancer Registry. No excess risk was found for colorectal cancer as such. The data were also analyzed by subsite of the large bowel for the index cases and for the spouses, respectively. The estimated relative risks were in general close to unity, the only exception being the risk of right-sided colon cancer among husbands of index cases with left-sided colon cancer, RR = 2.17 (p less than 0.05). The absence of excess risk was noted regardless of the duration of marriage. The risk of other cancers with a presumed etiology similar to that of colorectal cancer (cancer of the uterine corpus, breast, prostate and biliary tract) was also close to expected values.     

Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of environmental tobacco smoke and lung cancer: a case-control study in Japanese nonsmoking women

Genetic backgrounds may modify the association of environmental tobacco smoke (ETS) with lung cancer risk. Polymorphisms of both the activating and detoxifying enzymes, cytochrome P4501A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1), may be important as genetic factors. We conducted a multicenter case-control study in Japanese nonsmoking women. Cases were women aged 30-89 years and newly diagnosed as having lung cancer from November 1997 to March 2001 in 4 study areas. We also recruited age-matched (5-year strata) and hospital-matched nonsmoking controls. A total of 158 cases and 259 hospital controls supplied blood for genotyping. Detailed information on ETS exposure from husbands and that in other situations and on potential confounders was collected by interview. Odds ratios (ORs) were estimated by using conditional logistic models. We found no increase in the risk of lung cancer for CYP1A1 Msp I genotypes. For the GSTM1 null genotype vs. nonnull genotype, the OR was 1.37 [95% confidence interval (CI) 0.90-2.09], which indicated a somewhat increased risk for the GSTM1 null genotype. A gene-environment interaction was suggested, with combined GSTM1 null genotype and high-dose ETS exposure (>/=40 pack-years by husbands) conferring significantly higher risk (OR = 2.27, 95% CI 1.13-4.57) compared to the GSTM1 nonnull genotype and low-dose ETS exposure (<40 pack-years). Our results do not support a major role of Msp I polymorphism of the CYP1A1 gene as a risk factor for lung cancer among nonsmoking women. In contrast, the GSTM1 null genotype posed an increased, although not significant, risk among them. Additional studies are warranted to confirm the ETS-GSTM1 polymorphism interaction suggested in our present study.     

p53 mutations and exposure to environmental tobacco smoke in a multicenter study on lung cancer

Biomarker data may provide a way to strengthen the link between environmental tobacco smoke (ETS) exposure and lung cancer shown in epidemiological studies. We conducted a multicenter case-control study to investigate the association between ETS exposure and lung cancer in never-smokers using p53 mutations as a biomarker of tobacco-related carcinogenesis. Paraffin-embedded tissue or fresh tissue samples from 91 never-smokers and 66 smokers with histologically confirmed lung cancer and interview data about smoking habits and ETS exposure were analyzed for mutations in the p53 gene. Statistical analysis was performed using multivariate logistic regression. Among the lifelong nonsmokers, the overall mutation prevalence was 10% (nine cases). Among 48 never-smokers ever exposed to spousal ETS, 13% (six cases) showed mutations. Smokers exhibited 17 (26%) mutations. A 3-fold [odds ratio, 2.9; 95% confidence interval (CI), 1.2-7.2] increased risk of p53 mutation was observed for smokers as compared with all never-smokers combined (i.e., irrespective of ETS exposure). The increase was 4.4-fold (95% CI, 1.2-16.2) when compared with never-smokers without ETS exposure. Among never-smokers, the risk of mutation was doubled (odds ratio, 2.0; 95% CI, 0.5-8.7) for exposure to spousal ETS only, based on 6 exposed cases with mutation and 42 exposed cases without mutation. The risk was 1.5 (95% CI, 0.2-8.8) for those ever exposed to spousal or workplace ETS as compared with those never exposed to spousal or workplace ETS. For smokers, the most common mutation type was G:C to T:A transversion (31%), whereas G:C to A:T transitions were predominant among never smokers (57%). In conclusion, our study indicates a significant 3-4-fold increased risk of p53 mutation in smoking lung cancer cases, and it suggests that mechanisms of lung carcinogenesis in ETS-exposed never-smokers include mutations in the p53 gene, similar to that seen in smokers. However, the mutation patterns observed also suggest a difference between smokers and never-smokers. Clearly, additional investigations of the role of p53 mutation as a biomarker for tobacco-related carcinogenesis, including that related to ETS, are indicated.     

Risk factors for lung cancer among nonsmoking women

To evaluate risk factors for lung cancer in nonsmoking women, we used data of a case-control study conducted between 1991 and 1996 in Germany. A total of 234 female histologically confirmed lung cancer patients and 535 population controls who had never smoked more than 400 cigarettes in their lifetime were personally interviewed with respect to occupation, exposure to environmental tobacco smoke (ETS), family history of cancer, prior physician-diagnosed lung diseases or cancer and diet. One-year radon measurements in the last dwelling were performed. Odds ratios (OR) adjusted for age and region and 95% confidence intervals (CI) were calculated via logistic regression. When cumulative duration of exposure to ETS in hours was considered, the OR for high compared to not or low ETS exposed women was 2.62 (CI:1.35-5.06) for occupational exposure and OR=1.67 (CI:0.86-3.25) for spousal exposure, exhibiting a significant trend for ETS at work. Working more than 10 years in jobs or industries with known or suspected lung carcinogens was associated with OR=2.0 (CI:0.99-4.0). An elevated risk due to prior lung diseases was present for pneumonia (OR=1.6; CI:1.07-2.40) and tuberculosis (OR=1.6; CI:0.77-3.37). No significant increase in risk with increasing residential radon levels or with the presence of a family history of lung cancer was apparent. Protective effects were observed for high vs. low consumption of fresh vegetables (OR=0.5; CI:0.25-0.82) and cheese (OR=0.3, CI:0.21-0.55). ETS at work, occupational hazards and previous pneumonia may be risk factors for lung cancer in nonsmoking women, while a diet rich in fresh vegetables and cheese seems to be protective.     

Lifetime residential and workplace exposure to environmental tobacco smoke and lung cancer in never-smoking women, Canada 1994-97

Although the risk of lung cancer among never-smokers living with a spouse who smokes has been extensively studied, the impact of lifetime residential and workplace environmental tobacco smoke has received less attention. As part of a large population-based case-control study of lung cancer, we collected lifetime residential and occupational passive smoking information from 71 women with lung cancer and 761 healthy control subjects, all of whom reported being lifetime nonsmokers. The adjusted odds ratio (OR) for lung cancer associated with residential passive exposure only was 1.21 (95% confidence interval [CI] 0.5-2.8). Although more years of and more intense residential passive smoke exposure tended to be associated with higher risk estimates, no clear dose-response relationship was evident. The OR for women with passive exposure as a child and as an adult was 1.63 (95% CI 0.8-3.5) and for those only exposed as an adult 1.20 (95%CI 0.5-3.0). Exposure to environmental tobacco smoke only in the workplace was associated with an adjusted OR of 1.27 (95% CI 0.4-4.0). Risks associated with increasing occupational exposure year tertiles were 1.24, 1.71 and 1.71. Total smoker-years of residential and occupational exposure combined resulted in a statistically significant trend (linear test for trend p = 0.05) with ORs for tertiles of exposure of 0.83, 1.54 and 1.82. Our results are consistent with the literature suggesting that long-term, regular exposure to either residential or occupational environmental tobacco smoke is associated with increased lung cancer risk in never-smoking women.     

Difficulty becoming pregnant and family history as interactive risk factors for postmenopausal breast cancer: the Iowa Women's Health Study

We recently provided data from a prospective cohort study of postmenopausal women which suggested that a first livebirth at age 30 or older (cf before age 20) was associated with a twofold increased risk of breast cancer in women without a family history, but a 5.8-fold higher risk in women with a positive family history. To address the question of whether these observations reflect difficulty becoming pregnant or maintaining a pregnancy, we performed additional analyses in which the outcome of each pregnancy was considered. During five years of follow-up, 620 incident cases of breast cancer were identified in the 37,105 women at risk. There was little evidence for an increased risk associated with a history of spontaneous abortion (relative risk [RR]=1.1; 95 percent confidence interval [CI]=0.9–1.4), nor was the risk higher among women who reported two or more spontaneous abortions in consecutive pregnancies (RR=1.0, CI=0.7–1.4). Although women who reported that they had tried unsuccessfully to become pregnant had only slightly and nonsignificantly elevated risks of breast cancer (RR=1.1, CI=0.9–1.3), a more pronounced and statistically significant association was noted in women with a positive family history (RR=2.0, CI=1.4–3.2). There was a strong inverse association between failure to become pregnant and parity (P<0.0001); nearly 50 percent of the nulliparous married women reported having tried and failed to become pregnant, whereas the frequency was only 6.8 percent among married women with five or more livebirths. Thus, difficulties in becoming pregnant may characterize a subset of women at increased risk of breast cancer, especially in the presence of a family history.The authors are with the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Dr Sellers is also affiliated with the Institute of Human Genetics, University of Minnesota School of Medicine. Address correspondence to Dr Sellers, Division of Epidemiology, Suite 300, 1300 South Second Street, Minneapolis, MN 55454-1015. This publication was supported by a grant (RO1 CA39742) from the US National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.     

Passive smoking and lung cancer among Japanese women

A case-control study conducted in Hiroshima and Nagasaki, Japan, revealed a 50% increased risk of lung cancer among nonsmoking women whose husbands smoked. The risks tended to increase with amount smoked by the husband, being highest among women who worked outside the home and whose husbands were heavy smokers, and to decrease with cessation of exposure. The findings provide incentive for further evaluation of the relationship between passive smoking and cancer among nonsmokers.     

CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women

Polymorphisms in metabolic genes encoding phase I and phase II enzymes are thought to modulate the risk of lung cancer via changes in enzymatic activity. Recently, the effect of these metabolic enzymes and their interaction with environmental factors has been studied in both smokers and also never-smokers, since never-smokers are a good model in which to study genetic susceptibility at low-dose carcinogen exposure. Here, we investigated the association of CYP1A1 Ile462Val, CYP1B1 Leu432Val, GSTP1 Ile105Val, MPO G-463A polymorphisms and lung cancer risk in never-smoking Korean women. In this case-control study of 213 lung cancer patients and 213 age-matched healthy controls, we found that carrying one variant allele of the CYP1A1 Ile462Val polymorphism was associated with a significantly decreased risk of lung adenocarcinoma (adjusted odds ratio (OR)=0.63; 95% confidence interval (CI), 0.41-0.99). Furthermore, the combination of risk genotypes of CYP1B1 Leu432Val with CYP1A1 Ile462Val was associated with the risk of lung adenocarcinoma (adjusted OR=2.16; 95% CI, 1.02-4.57) as well as overall lung cancer (adjusted OR=2.23; 95% CI 1.01-4.89). The polymorphisms of GSTP1 Ile105Val and MPO G-463A showed no significant association with lung cancer. Theses results suggest that the CYP1A1 Ile462Val polymorphism is associated with a reduced risk of lung adenocarcinoma in never-smoking Korean women, whereas specific combinations of variant genotypes for metabolic enzymes increase lung cancer risk considerably.     

Passive smoking and lung cancer in Chandigarh, India.

The aim of this study is to assess the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers, a case-control study among lifetime non-smokers was conducted in Chandigarh, India. Cases consisted of 58 non-smoking histologically confirmed lung cancer patients; two controls for each case were selected, one among other patients admitted to the wards and one among the visitors to hospital patients. Subjects were asked about ETS exposure from different tobacco products in childhood and in adulthood at home, at the work place and in vehicles. Multivariate logistic regression analysis was used to assess the effects of the ETS exposure variables on lung cancer. Exposure to ETS during childhood was strongly associated with lung cancer (odds ratio (OR) = 3.9; 95% confidence interval (CI) = 1.9-8.2), the effect mostly arising from exposure to cigarettes smoke. The excess risk was observed with either a smoking father or mother. An increasing risk was found with increasing number of smokers and duration of exposure. Restricting the analysis to women produced higher estimates of the risk. No increased risk was found with exposure to a smoking spouse, except for those exposed only to cigarette smoke (OR = 5.1; 95% CI = 1.5-17). A weak association was seen between lung cancer and ETS exposure at the workplace, which increased with the number of years of exposure. Exposure in vehicles also was detected as a risk factor for lung cancer in non-smokers. This study suggests that ETS exposure may be a strong risk factor for lung cancer also in India, a country with low prevalence of smoking and, therefore, low rates of lung cancer. Other studies need to be conducted in similar settings to confirm the role played by ETS exposure early in life in the causation of lung cancer.     

Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis

A meta-analysis was carried out to calculate a pooled estimate of relative risk of lung cancer following exposure to environmental tobacco smoke (ETS) and to determine whether there was any heterogeneity in the pooled estimates according to selected characteristics of the studies. A total of 35 case-control and five cohort studies providing quantitative estimates of the association between lung cancer and exposure to ETS published between January 1981 and March 1999 were identified. Using fixed- and random-effects models, we calculated pooled estimates of relative risk for exposure to ETS from subjects' parents (during childhood), spouses, and coworkers. As well, we investigated whether the pooled estimates of relative risk varied by study location, degree of control of potential confounding variables, proportion of cases confirmed histologically, proportion of surrogate respondents, nonresponse rates, and year of publication. The relative risk of lung cancer among non smoking women ever exposed to ETS from their husbands' smoking was 1.20 (95% confidence interval (CI): 1.12-1.29). The pooled relative risk was 1.19 (95% CI: 1.10-1.29) for case-control studies and 1.29 (95% CI: 1.04-1.62) for cohort studies. In various subgroup and meta-regression analyses, we found no statistically significant differences by selected characteristics of the studies. In addition, we found that the risk of lung cancer increased consistently with increasing levels of exposure. The 11 studies reporting relative risks among male non smokers yielded a pooled relative risk of 1.48 (95% CI: 1.13-1.92) for ever exposed to ETS, and the relative risk of lung cancer for ever being exposed to ETS at work was a 1.16 (95% CI: 1.05-1.28). These results are consistent with the hypothesis that exposure to ETS increases the risk of lung cancer. While there may be alternative explanations to the data, it is more likely that the observed association is not an artifact and that ETS causes lung cancer in non smokers.