Cigarette smoking and risk of epithelial ovarian cancer (Australia)

Objectives: We studied the association between cigarette smoking and ovarian cancer in a population-based case–control study. Methods: A total of 794 women with histologically confirmed epithelial ovarian cancer who were aged 18–79 years and resident in one of three Australian states were interviewed, together with 855 controls aged 18–79 years selected at random from the electoral roll from the same states. Information was obtained about cigarette smoking and other factors including age, parity, oral contraceptive use, and reproductive factors. We estimated the relative risk of ovarian cancer associated with cigarette smoking, accounting for histologic type, using multivariable logistic regression to adjust for confounding factors. Results: Women who had ever smoked cigarettes were more likely to develop ovarian cancer than women who had never smoked (adjusted odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.2–1.9). Risk was greater for ovarian cancers of borderline malignancy (OR = 2.4; 95% CI = 1.4–4.1) than for invasive tumors (OR = 1.7; 95% CI = 1.2–2.4) and the histologic subtype most strongly associated overall was the mucinous subtype among both current smokers (OR = 3.2; 95% CI = 1.8–5.7) and past smokers (OR = 2.3; 95% CI = 1.3–3.9). Conclusions: These data extend recent findings and suggest that cigarette smoking is a risk factor for ovarian cancer, especially mucinous and borderline mucinous types. From a public health viewpoint, this is one of the few reports of a potentially avoidable risk factor for ovarian cancer.     

Cigarette smoking and breast cancer risk among young women (United States)

Objectives: To evaluate whether heavy cigarette smoking as a teenager or long-term smoking increases breast cancer risk or, alternatively, whether smoking acts as an anti-estrogen and reduces risk.Methods: Data from a multi-center, population-based, case-control study among women under age 55 were analyzed.Results: Among women under age 45, there was a modest inverse relation with current (OR=0.82, 95% CI=0.67, 1.01) but not past (OR=0.99, 95% CI=0.81, 1.21) smoking. Odds ratios were decreased for current smokers who began at an early age (0.59 for15, 95% CI=0.41, 0.85) or continued for long periods of time (0.70 for >21 years, 95% CI=0.52, 0.94). In subgroup analyses, reduced odds ratios were observed among current smokers who were ever users of oral contraceptives (0.79, 95% CI=0.63, 0.98), were in the lowest quartile of adult body size (0.53, 95% CI=0.34, 0.81), or never or infrequently drank alcohol (0.68, 95% CI=0.47, 0.98). Among women ages 45-54, there was little evidence for an association with smoking.Conclusions: These results suggest that breast cancer risk among women under age 45 may be reduced among current smokers who began smoking at an early age, or long-term smokers, but require confirmation from other studies.     

Allergy and risk of breast cancer among young women (United States)

Objective: To investigate the relationship between allergy and risk of breast cancer in women 45 years of age and younger. Methods: Data were analyzed from a population-based case–control study of breast cancer in western Washington. Cases were women born after 1944 who were diagnosed with invasive breast cancer (n = 747) between January 1983 and April 1990. Controls (n = 958) were similarly aged women ascertained through random-digit dialing. Cases and controls were interviewed about their history of doctor diagnosed allergies, including detailed information on the specific types of allergies and the age of onset. Using logistic regression we examined the associations between allergy history and breast cancer. Results: A history of allergies was associated with a reduced risk of breast cancer for women older than 35 (odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.60–0.99), but not for women 35 years or younger (OR = 1.30; 95% CI = 0.94–1.81). There was little difference in effect when age of first allergy onset was examined. No specific type of allergy was associated with breast cancer risk. Conclusion: Our results provide some evidence that a history of allergy may be associated with a reduced risk of breast cancer for women who develop breast cancer between 35 and 45 years of age. Future studies are needed to verify the relationship between immune responses and breast cancer risk.     

Association of NAT2 and smoking in relation to breast cancer incidence in a population-based case-control study (United States)

Objective: To evaluate the potential interaction between N-acetyltransferase 2 (NAT2) and smoking in breast cancer incidence. Methods: The data are derived from a population-based case–control study of women aged 20–69 years who were residents of Massachusetts or Wisconsin during 1997–1998. Incident cases of invasive breast cancer were identified through state tumor registries and age-similar controls were selected at random from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors including smoking history. Women provided oral mucosal DNA through the mail for genetic studies. Results: A total of 791 cases and 797 controls were included in the analysis. Overall, smoking was modestly associated with breast cancer risk (multivariate odds ratio (OR) for ever smoking: 1.37; 95% confidence interval (CI): 1.12–1.69), and there was a trend in risk for greater pack-years of smoking among postmenopausal women (p for trend = 0.02). Overall, NAT2 was not related to invasive breast cancer (multivariate OR: 1.11; 95% CI: 0.90–1.36). Associations of smoking with breast cancer tended to be somewhat stronger among the women with the slow acetylator genotype for NAT2: when compared to those who never smoked and were rapid acetylators, the OR for ever smoking was 1.50 (95% CI: 1.11–2.02) in slow acetylators, and OR: 1.24 (95% CI: 0.91–1.70) in rapid acetylators. However, tests for multiplicative interaction were not significant in case–control comparisons, or in case-only analyses. Conclusion: Results of the study are compatible with the majority of previous studies that indicate little or no association of NAT2, smoking, or their interaction with the occurrence of breast cancer.     

Weight change and risk of postmenopausal breast cancer (United States)

Objective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case–control study of postmenopausal breast cancer. Methods: Participants included women aged 50–79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84–0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95–1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06–1.11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.     

Active and passive tobacco smoking and the risk of borderline and invasive ovarian cancer (United States)

Objective: A population-based case–control study was conducted to examine the hypothesis that active and passive tobacco smoking were associated with the risk of epithelial ovarian cancer. Methods: In-person interviews were obtained from 558 women with epithelial ovarian cancer (431 invasive, 127 borderline) and 607 population controls regarding active lifetime tobacco smoking, environmental tobacco smoke exposure in utero and during childhood, and other factors that may be related to the development of ovarian cancer. Results: No significant associations of ever or former tobacco smoking with the risk of invasive or borderline ovarian cancer were found, although long-term ex-smokers of 20 years or more were at significantly reduced risk of invasive cancer. Significant, positive dose–response relations of the number of cigarettes smoked per day and pack-years with the odds ratios for borderline cancer were evident. No association of active tobacco smoking with risk was found by histologic subtype of invasive ovarian cancer. Smokers were at significantly increased risk for borderline serous cystadenoma (OR: 1.91; 95% confidence intervals, CI: 1.09–3.34), but not for borderline mucinous cystadenoma. When we limited the analyses to current smokers, age-started smoking was significantly inversely related to the risk of invasive, but not borderline ovarian cancer. We found no association of gestational or childhood environmental tobacco smoke exposure with the risk of invasive or borderline ovarian cancer among never smokers. Conclusions: These findings do not support an association of active tobacco smoking with the risk of invasive ovarian cancer. An increased risk of borderline serous cystadenoma among smokers must be viewed with caution.     

Reproductive factors,glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk

We conducted a hospital-based case–control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.     

Smoking during pregnancy and breast cancer risk in very young women (United States)

Objective: To evaluate the association of smoking during a woman's first pregnancy, a period of pronounced growth and differentiation of mammary tissue, and her subsequent breast cancer risk. Methods: In this matched case–control study, we used linked birth certificate and tumor registry data from the New York State Health Department. Cases were 319 women aged 26–45 who were diagnosed with breast cancer in New York State between 1989 and 1995 and who completed a first pregnancy in New York State after 1987 at least one year prior to diagnosis of cancer. Controls were 768 primiparous women matched to cases on county of residence and delivery date. Information on prenatal smoking and other factors characterizing the woman's first pregnancy was obtained from the pregnancy record of each subject, and the association of these factors to breast cancer risk was assessed using conditional logistic regression. Results: Smoking during pregnancy was associated with increased risk for breast cancer (crude OR = 2.7, 95% confidence interval (CI): 1.1–6.3). Adjustment for maternal age, subject age, race, and education strengthened this association (OR = 4.8, CI 1.6–14.6). Conclusions: These findings suggest that cigarette smoking during a woman's first pregnancy may increase her risk for early-onset breast cancer.     

Birth weight and risk of early-onset breast cancer (Denmark)

Objective: To investigate if birth weight is associated with early-onset breast cancer. The mechanism behind an association with high birth weight could be the link between fetal growth and estrogens in utero. Methods: We conducted a population-based case–control study in Denmark including 881 women with breast cancer diagnosed before the age of 40 years and 3423 age-matched controls. Information concerning birth weight and other birth-related variables was obtained from midwife reports. Results: The risk of early-onset breast cancer was increased 1.25 times (95% CI 1.00–2.51) for birth weights above 4000 g and 1.59 times (95% CI 1.00–1.55) for birth weights below 2500 g in comparison with birthweights of 3000–3499 g. Conclusions: The finding that high birth weight is associated with breast cancer is compatible with the hypothesis that level of estrogen during pregnancy is related to breast cancer in early adult life. The finding that low birth weight is also associated with breast cancer may indicate that other characteristics of the fetal environment may be important for breast cancer in early adult life.     

Obesity and the risk of prostate cancer (United States)

The role of obesity in prostate cancer etiology remains controversial. A recent report suggested that obese men younger than age 60 may have a lower risk of developing prostate cancer than men the same age who are not obese. The current study used a nested, matched case–control study design and data collected in the General Practice Research Database between January 1991 and December 2001 to assess the association between body mass index (BMI) and the risk of incident prostate cancer. Seven hundred and thirty cases of prostate cancer with adequate information on BMI were identified and matched to 2740 controls on age, sex, general practice, and index date. Obese men (BMI ≥ 30.0 kilograms [kg]/square of height in meters [m²]) were at lower risk of developing prostate cancer (AOR=0.78, 95% CI: 0.56, 1.09) compared to normal weight men (BMI=23.0–24.9 kg/m²), and the data best fit an inverse quadratic model for the relation between BMI and the risk of prostate cancer. This study provides modest support for a protective association between obesity and the risk of incident prostate cancer.     

GSTM1 and GSTT1 Polymorphisms, Cigarette Smoking, and Risk of Colon Cancer: A Population-based Case-control Study in North Carolina (United States)

Cigarette smoke is a risk factor for colon cancer, but the importance of dose and interaction with genetic susceptibility remain poorly understood. We used data from a population-based case control study, to examine the association between cigarette smoking and colon cancer in African Americans and whites, and colon cancer and polymorphisms in GSTM1 and GSTT1. A total of 554 cases of primary colon cancer and 874 controls were included in this analysis. We found no association between cigarette smoking (ever versus never) and colon cancer in African Americans (odds ratio (OR)=0.93, 95% confidence interval (CI)=0.65–1.33). In contrast, there was an increased risk of cigarette smoking in whites (OR=1.43, CI=1.05–1.94). There was a small increased risk of colon cancer for individuals with GSTM1 null (African Americans, OR=1.43, CI, 0.98–2.09; whites, OR=1.19, CI, 0.90–1.58) and a decreased risk of colon cancer for individuals with GSTT1 null (African Americans, OR=0.59, CI: 0.40–0.86; whites, OR=0.72, CI: 0.53–1.00). There were weak interactions between GSTT1 null and cigarette smoking in whites, and GSTM1 null genotype and cigarette smoking in African Americans. GSTT1 and GSTM1 polymorphisms may be weakly related to colon cancer risk and there may be racial differences in gene-smoking interactions.     

Cytochrome P450 1A1, cigarette smoking,and risk of endometrial cancer (United States)

Cytochrome P450 1A1 (CYP1A1) is involved in the metabolism of estradiol and the activation of polycyclic aromatic hydrocarbons found in tobacco products. Polymorphic variation in CYP1A1 activity may modify susceptibility to endometrial cancer through the oxidative metabolism of estradiol and the activation of tobacco-smoke constituents. We prospectively evaluated the associations between three common CYP1A1 polymorphisms and endometrial cancer risk, as well as the potential modification of these associations by cigarette smoking, in a case–control study nested within the Nurses’ Health Study. We investigated the MspI restriction-site polymorphism, a C → A transversion at nucleotide 4887 (Thr461Asn) and a A → G transition at nucleotide 4889 (Ile462Val) among 456 women with endometrial cancer and 1,134 matched controls. We used conditional logistic regression to calculate the adjusted odds ratios (OR) and 95% confidence intervals (CI) to quantify the risk of endometrial cancer among subjects who had at least one variant allele compared with that of subjects homozygous for the wild-type allele. We did not observe any statistically significant associations between the MspI, Thr461Asn or Ile462Val polymorphisms and endometrial cancer risk or any significant effect modification by cigarette-smoking status. These data suggest that these three polymorphisms are not important in determining genetic susceptibility to endometrial cancer, although larger sample sizes are needed to confirm these findings.     

Glutathione S-transferase M1 and T1 genetic polymorphisms,alcohol consumption and breast cancer risk

Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case-control study in the state of Connecticut in the period 1998 and 2001. Cases were histologically confirmed, incident breast cancer patients in New Haven County, CT. Controls were randomly selected from women histologically confirmed to be without breast cancer. The study results show that, while GSTM1 genotypes were not associated with breast cancer risk, GSTT1-null genotype was associated with a significant 90% increased risk for postmenopausal women (OR=1.9, 95% CI 1.2-3.0). Analysis by GST genotypes and alcohol consumption shows that GSTM1A ever-drinking women had a 2.5-fold (OR=2.5, 95% CI 1.1-5.5) increased risk of breast cancer compared to the GSTM1A never-drinkers, and the risk increases with duration and daily amount of alcohol consumption. Postmenopausal women with GSTT1-null genotype, who consumed a lifetime of >250 kg of spirit-equivalents, had an almost seven-fold increased risk (OR=6.8, 95% CI 1.4-33.9), and drinking commencing at younger ages appears to carry a higher risk. An OR of 8.2 (95% CI 1.2-57.4) was observed for those with GSTM1A, and GSTT1-null genotypes who had consumed a lifetime of >250 kg of spirit-equivalents. In conclusion, alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes.     

Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States)

Objective: Insulin-like growth factor I (IGF-I) exerts potent mitogenic and antiapoptotic effects on prostatic epithelial cells. Insulin-like growth factor binding protein-3 (IGFBP-3) modulates the effects of IGF-I, and independently induces apoptosis and inhibits cell growth. Previous studies have inconsistently associated IGF-I and IGFBP-3 with prostate cancer. To try and further clarify these potential associations, we undertook a sibling-matched case–control study. Methods: Serum IGF-I and IGFBP-3 were determined for 845 men (408 cases and 437 sibling controls). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the serum IGF levels and prostate cancer. Results: Among all study subjects, only the molar ratio of IGF-I to IGFBP-3 was associated with prostate cancer: comparing those in the highest to lowest quartiles gave an OR = 1.62 (95% CI = 1.02–2.57, trend-p = 0.04). Among men with clinically less aggressive disease, we observed positive associations between prostate cancer and high levels of IGF-I (OR = 2.78, 95% CI = 1.06–6.80, trend-p = 0.03), and IGFBP-3 (OR = 2.68, 95% CI = 1.08–6.80, trend-p = 0.04). Simultaneously modeling both left the IGF-I result essentially unchanged, while substantially weakening the IGFBP-3 association. Conclusions: We found that a high IGF-I to IGFBP-3 molar ratio was associated with an increased risk of prostate cancer. Furthermore, high IGF-I was associated with increased risk of prostate cancer among men with less advanced disease at diagnosis. These results lend support to the hypothesis that IGF-I, or the IGF-I to IGFBP-3 molar ratio, is an important risk factor for prostate cancer.     

Glutathione S-transferase M1 and T1 Polymorphisms,Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles.The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned toevaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. Thestudy was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minorgynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attendingthe cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) usingL1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures.Differences in proportions were tested using Pearson’s Chi-square test with Odds ratio (OR) and 95% confidenceinterval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype(OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes wasobserved in women with normal, precancerous and cervical cancerous lesions among ≤35 or >35 years of agegroups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers(OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervicalcancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) andGSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive nonsmokers. The results demonstrate that the GST null genotypes were alone not associated with the developmentof cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.     

Cigarette smoking and breast cancer risk: a population-based study in Sweden

In a Swedish population-based case-control study, smoking showed no convincing association with risk of postmenopausal breast cancer - regardless of timing or level of smoking exposure - either overall or among subgroups.     

Cigarette Smoking, Alcohol Consumption, and Endometrial Cancer Risk: A Population-based Study in Sweden

Objective: To assess effects of cigarette smoking and alcohol consumption on the risk of endometrial cancer among postmenopausal women. Methods: We performed a nationwide population-based case–control study among postmenopausal women aged 50–74 years in Sweden, including 709 incident endometrial cancer cases and 3368 controls. Results: Compared to never smokers, recent/current smokers had a decreased risk of endometrial cancer (multivariate OR 0.61, 95% CI 0.47–0.80), but former smokers presented no substantial difference in risk (multivariate OR 0.90, 95% CI 0.72–1.14). We observed a decreased risk of endometrial cancer for postmenopausal smoking, but there was no clear impact on risk for premenopausal smoking. The inverse association of smoking with risk was not explained by differences in body mass index between smokers and nonsmokers. Alcohol consumption was not clearly associated with risk of endometrial cancer. The multivariate OR for women consuming up to 1.6 g of alcohol per day was 1.12 (95% CI 0.88–1.44), and 0.92 (95% CI 0.70–1.20) for women consuming more than 4 g per day (p for trend over categories=0.44). Conclusions: Current cigarette smoking reduces the risk of postmenopausal endometrial cancer, but the inverse association dissipates after smoking cessation. Premenopausal smoking might not affect risk of postmenopausal endometrial cancer. Alcohol consumption is not materially associated with risk.     

Transient increase in breast cancer risk after giving birth: postpartum period with the highest risk (Sweden)

Objective: Identify time-points when the elevated postpartum maternal breast cancer risk peaks. Methods: A case–control study nested within the Swedish Fertility Register included 34,018 breast cancer cases from the Swedish Cancer Register between 1961 and 1995. From the Fertility Register, 170,001 eligible subjects matched to the cases by age were selected as controls. Analysis contrasted risk between uniparous (7084 cases and 31,703 controls) and nulliparous (5411 cases and 22,580 controls) women and between biparous (13,239 cases and 65,858 controls) and uniparous women. Logistic regression analysis included indicator variables representing each year of age, ages at delivery, and time since delivery. Results: Comparing uniparous with nulliparous women the transient increase in maternal breast cancer risk peaked 5 years following delivery (odds ratio = 1.49, 95% confidence interval 1.01–2.20) and leveled off 15 years postpartum. Biparous women had a transient increase in risk that was lower at its peak than that of uniparous women, occurring about 3 years following second delivery. Conclusions: A time window of 5 years postpartum when maternal breast cancer risk is highest was observed. Establishing timing of peak transient increase in postpartum breast cancer risk may define the latent period required for pregnancy hormones in promoting progression of breast cells that have undergone early stages of malignant transformation.     

Active cigarette smoking and risk of breast cancer

Although epidemiological evidence on the role of active cigarette smoking in breast cancer risk has been inconsistent, recent literature supports a modest association between smoking and breast cancer. This association is particularly observed in women who smoke for a long duration, or who smoke for a long time prior to their first pregnancy. Here, we provide updated results on cigarette smoking and breast cancer risk in the Canadian National Breast Screening Study (NBSS). The NBSS is a large cohort of 89,835 women, aged 40–59, who were followed for a mean of 22.1 years, resulting in the ascertainment of 6,549 incident cases of breast cancer. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cigarette smoking variables with breast cancer risk. We found breast cancer to be associated with duration (40 years vs. 0: HR = 1.57; 95%CI = 1.29–1.92), intensity (40 cigarettes per day vs. 0: HR = 1.21; 95%CI = 1.04–1.40), cumulative exposure (40 pack‐years vs. 0: HR = 1.19; 95%CI = 1.06–1.13) and latency (40 years since initiation vs. 0: HR = 1.19; 95%CI = 1.10–1.53) of cigarette smoking. Number of years smoked prior to first full‐term pregnancy was associated with higher risk of breast cancer than comparative years smoked post‐pregnancy (among parous women, 5 years pre pregnancy vs. 0: HR = 1.18; 95%CI = 1.10–1.26). These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.