Smoking duration before first childbirth: an emerging risk factor for breast cancer? Results from 302,865 Norwegian women

This article is part of Eivind Bjerkaas' doctoral thesis which is available in Munin at http://hdl.handle.net/10037/6799Purpose: Recently, The International Agency for Research on Cancer classified cigarette smoking as possibly carcinogenic to the human breast. Since some new cohort studies have suggested that this risk is confined to women who started to smoke before first childbirth, we wanted to examine the association between smoking and breast cancer, with a focus on time of smoking initiation in relation to the first childbirth. Methods: We followed 302,865 Norwegian women born between 1899 and 1975, recruited from 1974 to 2003, by linkage to national registries through December 2007. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95 % confidence intervals (CI). Results: During more than 4.1 million person-years of follow-up, we ascertained 7,490 cases of primary invasive breast cancer. Compared with never smokers, ever smokers had a 15 % (HR = 1.15, 95 % CI 1.10–1.21) increased risk of breast cancer overall and also a significantly increased risk of breast cancer in the three most exposed categories of age at smoking initiation (parous women), number of cigarettes smoked per day, years of smoking duration and number of pack-years. Ever smokers who started to smoke more than 1 year after the first childbirth had not an increased risk (HR = 0.93, 95 % CI 0.86–1.02), while those who initiated smoking more than 10 years before their first childbirth had a 60 % (HR = 1.60, 95 % CI 1.42–1.80) increased risk of breast cancer, compared with never smokers

Aspects of Active Smoking and Breast Cancer

Summary: According to the WHO, breast cancer is by far the most frequently diagnosed cancer, and the most frequent cause of cancer death among women in the world. Tobacco smoking is the single largest cause of cancer worldwide and has been linked to cancer in most organ systems. The aim of this thesis was to illuminate the association between smoking and breast cancer incidence, mortality, and to study the socioeconomic consequences of smoking-associated breast cancer in a large Norwegian cohort with a high number of female smokers. In Paper I we investigated the association between active smoking and breast cancer incidence. We found an increased risk of 15% for ever smokers overall, as well as an increased breast cancer risk with increasing number of cigarettes smoked per day, smoking duration, number of pack-years smoked, and lower age at smoking initiation. We found an increasing risk with longer smoking duration before first childbirth, and no increased risk among those who started to smoke after first childbirth. In Paper II we investigated the association between smoking and breast cancer mortality, which revealed a 15% increased risk of breast cancer mortality for ever smokers. Most of the results for the different smoking exposures considered were not statistically significant. In Paper III, we used level of education as a validated measure of socioeconomic status, and investigated whether level of education had an impact on the risk of smoking-associated breast cancer. We did not find an increased risk of smoking-associated breast cancer in women with high level of education, but we were able to confirm that smoking before first childbirth remains a risk factor for breast cancer, regardless of educational achievement. Smoking-associated breast cancer does not seem to have an important impact on social inequalities in health. Active smoking, in particular active smoking before first childbirth, emerges as a risk factor for breast cancer incidence

Smoking increases rectal cancer risk to the same extent in women as in men: results from a Norwegian cohort study

Background: Smoking has recently been established as a risk factor for rectal cancer. We examined whether the smoking-related increase in rectal cancer differed by gender. Methods: We followed 602,242 participants (49% men), aged 19 to 67 years at enrollment from four Norwegian health surveys carried out between 1972 and 2003, by linkage to Norwegian national registries through December 2007. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazard models and adjusting for relevant confounders. Heterogeneity by gender in the effect of smoking and risk of rectal cancer was tested with Wald χ2. Results: During a mean follow-up of 14 years, 1,336 men and 840 women developed invasive rectal cancer. Ever smokers had a significantly increased risk of rectal cancer of more than 25% for both men (HR = 1.27, 95% CI = 1.11-1.45) and women (HR = 1.28, 95% CI = 1.11-1.48) compared with gender-specific never smokers. Men smoking ≥20 pack-years had a significantly increased risk of rectal cancer of 35% (HR = 1.35, 95% CI = 1.14-1.58), whereas for women, it was 47% (HR = 1.47, 95% CI = 1.13-1.91) compared with gender-specific never smokers. For both men and women, we observed significant dose–response associations between the risk of rectal cancer for four variables [Age at smoking initiation in years (both ptrend <0.05), number of cigarettes smoked per day (both ptrend <0.0001), smoking duration in years (ptrend <0.05, <0.0001) and number of pack-years smoked (both ptrend <0.0001)]. The test for heterogeneity by gender was not significant between smoking status and the risk of rectal cancer (Wald χ2, p -value; current smokers = 0.85; former smokers = 0.87; ever smokers = 1.00). Conclusions: Smoking increases the risk of rectal cancer to the same extent in women as in men

Cigarette smoking and colorectal cancer mortality among 602,242 Norwegian males and females

Background: Colorectal cancer (CRC) is one of the main cancer types, with high incidence and mortality in Norway. We examined the association between different measures of smoking exposure and CRC mortality overall and by subsite in a large Norwegian cohort. Methods: We followed 602,242 participants from four Norwegian health surveys, aged 19–67 years at enrollment between 1972 and 2003 by linkage to the national registries through December 2007. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) by smoking categories for different CRC endpoints. Results: During a mean follow-up of 14 years, 2,333 Norwegian males and females died of CRC (60% men). Male and female ever smokers had a 20% (HR 1.23, CI 1.08–1.40 and HR 1.22, 95% CI 1.06–1.40, respectively) increased risk of death from CRC compared with sex-specific never smokers. For proximal colon cancer mortality, female ever smokers had a 50% (HR 1.49, 95% CI 1.20–1.87) increased risk compared with female never smokers. The increased risk of rectal cancer mortality was about 40% higher for male ever smokers (HR 1.43, 95% CI 1.14–1.81) compared with male never smokers. A test for heterogeneity by sex showed an increased risk of rectal cancer mortality among men which was significant for former smokers (Wald χ2=0.02) and an increased risk of proximal colon cancer mortality among women which was significant for ever and former smokers (Wald χ2=0.02 and χ2=0.04, respectively). Conclusion: Smoking is associated with increased CRC mortality in both sexes. The risk of rectal and proximal colon cancer mortality was most pronounced among male and female smokers respectively

Social inequalities and smoking-associated breast cancer - Results from a prospective cohort study

Objective. The association between smoking and breast cancer has been found in most recent, large cohort studies. We wanted to investigate how smoking-associated breast cancer varies by level of education, a wellestablished measure of socioeconomic status. Methods. We included 302,865 women with 7490 breast cancer cases. Participants were assigned to low, moderate or high level of education and analyzed by smoking status (ever/never), and stratified by birth cohorts (≤1950N). We used Cox proportional hazard to estimate hazard ratios (HRs) and confidence intervals (CIs), adjusting for age, number of children, age at first childbirth, BMI, age at enrollment and physical activity. Results. Women born ≤1950 with low and moderate levels of education had a 40% increase in smokingassociated breast cancer risk (HR = 1.40, 95% CI 1.25–1.57 and HR = 1.14, 95% CI 1.05–1.24, respectively). Women in the same age group with high level of education did not have an increase in risk. No increased breast cancer risk was found among women born after 1950 for any level of education, when analyzed by smoking status. Longer duration of smoking before first childbirth was consistently associated with increasing risk of breast cancer in all three categories of education (all p for trends b 0.01). Conclusion. Smoking for several years before first childbirth increases the risk of breast cancer, regardless of educational level

Active and passive cigarette smoking and breast cancer risk: Results from the EPIC cohort

Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious