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.     

Hydatidiform moles and the long-term risk of breast cancer (Sweden)

Objectives: The etiology of breast cancer is only partially understood. Based on the findings that pregnancies reduce breast cancer risk, a possible inverse association between exposure to the placental hormone human chorionic gonadotropin (hCG) and the risk of breast cancer has been suggested. Hydatidiform mole, a gestational trophoblastic disease, is associated with a high expression of hCG. We performed a population-based cohort study in which women with a history of hydatidiform mole were followed up for future cancer outcomes. Methods: All 3371 women with a notification of hydatidiform mole in the Swedish Cancer Registry between 1958 and 1993 were followed up for future cancer outcomes by record linkages within the registry. Results: In a total of 57,075 person-years of follow-up, 59 women had a diagnosis of breast cancer during follow-up, yielding an overall standardized incidence ratio of 1.3 (95% CI 1.0–1.7). Conclusion: This finding is not consistent with the hypothesis of a protective effect of hCG exposure on breast cancer risk, but rather suggests an adverse association.     

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.     

Active and passive smoking and breast cancer risk in middle-aged Japanese women

To examine the hypothesis that tobacco smoke is associated with the risk of female breast cancer, we estimated the relative risks of active and passive smoke in middle-aged Japanese women in a population-based prospective study. The cohort consisted of residents in 4 public health center areas, aged 40 to 59 years. A self-administered questionnaire survey was conducted in 1990. This analysis included 21,805 subjects, 180 of whom had developed breast cancer by December 31, 1999. When the reference was defined as never-active smokers without passive smoking, adjusted relative risks (RRs) were 1.9 (95% confidence interval [CI] = 1.0-3.6) in current active smokers, 1.2 (95% CI = 0.4-4.0) in ex-active smokers and 1.2 (95% CI = 0.8-1.6) in never-active smokers with passive smoking. The elevated risk for ever-smokers was clearly observed in premenopausal women at baseline (RR = 3.9, 95% CI = 1.5-9.9) but not in postmenopausal women (RR = 1.1, 95% CI = 0.5-2.5). In never-active smokers, the adjusted RR for passive smoking, residential or occupational/public tobacco smoke exposure was 1.1 (95% CI = 0.8-1.6). In premenopausal women, passive smoking increased the risk (RR = 2.6; 95% CI = 1.3-5.2) but not in postmenopausal women (RR = 0.7; 95% CI = 0.4-1.0). We conclude that tobacco smoking increases the risk of female breast cancer in premenopausal women.     

Rapid N-acetyltransferase 2 imputed phenotype and smoking may increase risk of colorectal cancer in women (Netherlands)

Objective: The relationship between smoking and colorectal cancer risk and whether such effect is modified by variations in the NAT2 genotype is investigated. Methods: In the prospective DOM (Diagnostisch Onderzoek Mammacarcinoom; 27,722 women) cohort follow-up from 1976 until 1987 revealed 54 deaths due to colon or rectal cancer, and follow-up from 1987 to 01-01-1996 revealed 204 incident colorectal cancer cases. A random sample (n = 857) from the baseline cohort was used as controls. Four NAT2 restriction fragment length polymorphisms (RFLPs) were analysed using DNA extracted from urine samples. Rapid or slow acetylator phenotype status was attributed to individuals. Results: Smoking may increase the risk for colon cancer (RR = 1.36, 95% CI 0.97–1.92) as well as for rectal cancer (RR = 1.31, 95% CI 0.76–2.25), although not statistically significant. Rapid NAT2 acetylation did not increase colorectal cancer risk, but in combination with smoking the risk was statistically significant increased, compared to women who had a slow NAT2 imputed phenotype and never smoked (RR = 1.56, 95% CI 1.03–2.37). For colon cancer, but not for rectal cancer the increased risk was statistically significant (RR = 1.67, 95% CI, 1.05–2.67 versus RR = 1.30 95% CI 0.63–2.68). Conclusions: Our study points to smoking as a risk factor for colon and rectal cancer and, in addition, especially in women with rapid NAT2 imputed phenotype.     

Breast density and risk of breast cancer

Early studies reported a 4- to 6-fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case-control studies, we took advantage of a population-based screening program to study density and breast cancer incidence in a cohort design. In the Capital Region, Denmark, women aged 50 to 69 are invited to screening biennially. Women screened November 2012 to December 2017 were included, and classified by BI-RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RRs) and 95% confidence intervals (CI) were compared across density groups using Poisson-regression. We included 189 609 women; 1 067 282 person-years; and 4110 incident breast cancers/DCIS. Thirty-three percent of women had BI-RADS density code 1; 38% code 2; 24% code 3; 4.7% code 4; and missing 0.3%. Using women with BI-RADS density code 1 as baseline; women with code 2 had RR 1.69 (95% CI 1.56-1.84); women with code 3, RR 2.06 (95% CI 1.89-2.25); and women with code 4, RR 2.37 (95% CI 1.05-2.74). Results differed between observations accumulated during screening and above screening age. Our results indicated less difference in breast cancer risk across level of breast density than normally stated. Translated into absolute risk of breast cancer after age 50, we found a 6.2% risk for the one-third of women with lowest density, and 14.7% for the 5% of women with highest density.     

Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility

The influence of polymorphisms of the glutathione S-transferase gene GSTM1 in breast cancer susceptibility has been assessed in this study. Previous studies correlated the absence of the GSTM1 protein with an increased risk of developing some cancers, especially lung or bladder cancers, in heavy smokers. In this study, we determined GSTM1 polymorphisms in a population of 437 female controls from the west of France and 361 community breast cancer patients. Three distinct alleles of this gene exist: GSTM1* A, GSTM1*B and GSTM1*0 (deleted allele). Null subjects (GSTM1 null) are homozygous for this deletion. The comparative analysis of GSTM1 allelotypes in our two populations did not demonstrate a statistically significant difference in distribution (P = 0.22), although the null genotype was more frequent in cancer patients. However, breast cancer risk was increased in null subjects ≥ 50 years of age compared with non-null subjects [odds ratio = 1.99 (1.19–3.32), P = 0.009], but not in null subjects < 50 years of age compared with non-null subjects (P = 0.86). Our results suggest that the GSTM1 null genotype may play a role in post-menopausal breast cancer development. They also point to a putative protective role of the A allele in the older female control group, especially in hemizygous subjects [odds ratio = 0.42 (0.23–0.77), P = 0.03]. © 1999 Cancer Research Campaign     

Adherence to cancer prevention guidelines and risk of breast cancer

Healthy eating patterns and keeping physically active are potentially more important for chronic disease prevention than intake or exclusion of specific food items or nutrients. To this end, many health organizations routinely publish dietary and lifestyle recommendations aimed at preventing chronic disease. Using data from the Canadian National Breast Screening Study, we investigated the association between breast cancer risk and adherence to two sets of guidelines specific for cancer prevention, namely the American Cancer Society (ACS) Guidelines and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Recommendations. At baseline, 49,613 women completed dietary and lifestyle questionnaires and height and weight measurements were taken. During a mean follow‐up of 16.6 years, 2,503 incident cases of breast cancer were ascertained. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of meeting each guideline, and number of guidelines met, with breast cancer risk. The two sets of guidelines yielded similar results. Specifically, adherence to all six ACS guidelines was associated with a 31% reduction in breast cancer risk when compared to subjects adhering to at most one guideline (HR = 0.69; 95% CI = 0.49–0.97); similarly, adherence to six or seven of the WCRF/AICR guidelines was also associated with a 31% reduction in breast cancer risk (HR = 0.69; 95% CI = 0.47–1.00). Under either classification, meeting each additional guideline was associated with a 4–6% reduction in breast cancer risk. These results suggest that adherence to cancer prevention guidelines is associated with a reduced risk of breast cancer.     

Alcohol consumption and cigarette smoking in combination: A predictor of contralateral breast cancer risk in the WECARE study

Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population‐based case‐control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24–2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18–1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08–2.08; p‐trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.     

Left-handedness and risk of breast cancer

Left-handedness may be an indicator of intrauterine exposure to oestrogens, which may increase the risk of breast cancer. Women (n=1786) from a 1981 health survey in Busselton were followed up using death and cancer registries. Left-handers had higher risk of breast cancer than right-handers and the effect was greater for post-menopausal breast cancer (hazard ratio=2.59, 95% confidence interval 1.11-6.03).     

Tubal sterilization and risk of breast cancer mortality in US women

Objective: To investigate the hypothesis that tubal sterilization is associated with a reduced risk of breast cancer. Methods: We examined this hypothesis in a large prospective study of US adults. After 14 years of mortality follow-up, 3837 deaths from breast cancer were observed in a cohort of 619,199 women who were cancer-free at study entry in 1982. Results: Cox proportional hazards models (adjusted for multiple breast cancer risk factors) showed a significant inverse association between tubal sterilization and breast cancer mortality (adjusted rate ratio (RR) = 0.82, 95% confidence interval (CI) 0.70–0.96). Women who were sterilized before age 35 had a lower risk (adjusted RR = 0.69, 95% CI 0.53–0.88) than women who were sterilized at 35 years of age or older (adjusted RR = 0.92, 95% CI 0.75–1.13). Also, sterilizations performed before 1975 resulted in a lower risk (RR = 0.75, 95% CI 0.62–0.91) than those performed during or after 1975 (RR = 0.98, 95% CI 0.74–1.29), possibly reflecting the likelihood of greater tissue damage with earlier procedures. Conclusions: These results suggest that tubal sterilization may lower subsequent risk of breast cancer, especially among women who are sterilized at a relatively young age. Additional studies are needed to confirm or refute these findings.     

Secondhand smoke exposure in early life and the risk of breast cancer among never smokers (United States)

Evidence is increasing that some early life exposures affect breast cancer risk. Exposure to secondhand smoke (SHS) during childhood may be one such exposure. As part of the WEB Study (Western New York Exposures and Breast Cancer Study), we conducted a population-based, case-control study with 1166 women aged 35 to 79 diagnosed with histologically confirmed, primary, incident breast cancer. Controls (n = 2105) were randomly selected from the Department of Motor Vehicles driver’s license list (≤age 65) and the Center for Medicare & Medicaid Services rolls (>age 65). Participants were queried regarding household and workplace SHS exposure. Person-years of lifetime cumulative SHS exposure were computed as well as cumulative exposure up to 21 years of age. Unconditional logistic regression adjusting for potential confounders was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Lifetime cumulative exposure to household SHS was not associated with an increase in breast cancer risk for premenopausal (OR = 1.17, 95% CI = 0.54–2.56) or postmenopausal (OR = 1.29; 95% CI = 0.82–2.01) women. Neither was risk increased among women exposed to SHS before the age of 21 or at the time of birth, menarche, or a women’s first birth. In this study, exposure to SHS either in adult or early life does not appear to be associated with the risk of breast cancer.     

Prospective study on the role of glucose metabolism in breast cancer occurrence

High circulating glucose, insulin resistance and obesity appear to be associated with increased risk of breast cancer (BC). We sought further insight into the relation of these variables to BC. We assessed associations of BC risk with serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) index and sex-binding hormone globulin (SHBG) in women recruited to the ORDET cohort who gave blood samples in 1987-1992. After a median 13.5 years of follow-up, 356 women developed BC. Four matched controls per case were selected by incidence density sampling, and rate ratios (RR) were estimated by conditional logistic regression. Women in the highest glucose quartile had a significantly greater risk of BC than those in the lowest glucose quartile (RR 1.63; 95% CI: 1.14-2.32; p for trend of 0.003). The association was significant in pre and post menopausal women separately and in women diagnosed after 55 years. Women in the highest HOMA-IR quartile had higher BC risk than the lowest quartile (RR 1.44; 95% CI: 1.03-2.02). Significantly increased BC risk in women diagnosed after 55 years was also present in the highest HOMA-IR quartile; in the same group decreased BC risk was significantly associated with high SHBG. The results of this study add to the existing epidemiological evidence that hyperglycemia and insulin resistance increase BC risk.     

Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC)

Smoking has recently been recognised as causally associated with the development of gastric cancer (GC). However, evidence on the effect by sex, duration and intensity of smoking, anatomic subsite and cessation of smoking is limited. Our objective was to assess the relation between tobacco use and GC incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC). We studied data from 521,468 individuals recruited from 10 European countries taking part in the EPIC study. Participants completed lifestyle questionnaires that included questions on lifetime consumption of tobacco and diet in 1991-1998. Participants were followed until September 2002, and during that period 305 cases of stomach cancer were identified. After exclusions, 274 were eligible for the analysis, using the Cox proportional hazard model. After adjustment for educational level, consumption of fresh fruit, vegetables and preserved meat, alcohol intake and body mass index (BMI), there was a significant association between cigarette smoking and gastric cancer risk: the hazard ratio (HR) for ever smokers was 1.45 (95% confidence interval [CI] = 1.08-1.94). The HR of current cigarette smoking was 1.73 (95% CI = 1.06-2.83) in males and 1.87 (95% CI = 1.12-3.12) in females. Hazard ratios increased with intensity and duration of cigarette smoked. A significant decrease of risk was observed after 10 years of quitting smoking. A preliminary analysis of 121 cases with identified anatomic site showed that current cigarette smokers had a higher HR of GC in the cardia (HR = 4.10) than in the distal part of the stomach (HR = 1.94). In this cohort, 17.6 % (95% CI = 10.5-29.5 %) of GC cases may be attributable to smoking. Findings from this large study support the causal relation between smoking and gastric cancer in this European population. Stomach cancer should be added to the burden of diseases caused by smoking.     

Changes in mammographic density over time in breast cancer cases and women at high risk for breast cancer

High mammographic breast density is one of the strongest intermediate markers of breast cancer risk, and decreases in density over time have been associated with decreases in breast cancer risk. Using repeated measures of mammographic density in a cohort of high‐risk women, the Women at Risk (WAR) cohort at Columbia University Medical Center (N = 2670), we examined whether changes in prediagnostic mammographic density differed among 85 prospectively‐ascertained breast cancer cases and 85 age‐matched controls, using a nested case–control design. Median age at first mammogram was 51 years (range, 29–77 years), with a median of 4 years between first and second prediagnostic mammogram (range, 1–15 years). Using linear regression with change in percent density as the outcome, we found that in women who did not go on to be diagnosed with breast cancer, change in percent density decreased as time between first and second mammogram increased (β = ?1.62% per year, p = 0.004). However, in women who did go on to be diagnosed with breast cancer, there was no overall change in percent density associated with time between first and second mammogram (β = 0.29% per year, p = 0.61); the change over time was statistically significantly different between cases versus controls (p <0.009). If replicated in larger cohorts, these results suggest that within‐individual changes in mammographic density as measured by percent density may be a useful biomarker of breast cancer risk.     

Nucleotide excision repair polymorphisms may modify ionizing radiation-related breast cancer risk in US radiologic technologists

Exposure to ionizing radiation has been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base-excision repair pathway, certain types of multiple-base damage can only be repaired through the nucleotide excision repair pathway. In a nested case-control study of breast cancer in US radiologic technologists exposed to low levels of ionizing radiation (858 cases, 1,083 controls), we examined whether risk of breast cancer conferred by radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (OR(GC) = 1.1, OR(CC) = 1.3; p-trend = 0.08), with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/Gy(GG) = 1.0, 95% CI = <0, 6.0; EOR/Gy(GC/CC) = 5.9, 95% CI = 0.9, 14.4; p(het) = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation dose on risk of breast cancer (EOR/Gy(AA) = 9.1, 95% CI = 2.1-21.3; EOR/Gy(AC/CC) = 0.6, 95% CI = <0, 4.6; p(het) = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk.     

Prospective study of alcohol consumption and breast cancer risk in Japanese women

Epidemiologic evidence is lacking for the association between alcohol consumption and the risk of breast cancer in Japanese women. We addressed this association in a prospective cohort study with an average follow-up of 7.6 years. At baseline (1988-1990), cohort participants completed a self-administered questionnaire that included alcohol use, reproductive history and hormone use. The women were followed up for breast cancer incidence through December 31, 1997. Cox proportional hazards models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer incidence and any association with alcohol consumption. During a follow-up of 271,412 person-years, we identified 151 women with breast cancer, of whom 45 were current drinkers and 11 drank > or =15 g of alcohol/day. After adjustment for age and other potential risk factors for breast cancer, the RR for current drinkers was 1.27 (95% CI 0.87-1.84) compared to nondrinkers. Average alcohol intake of <15 g/day did not significantly increase the risk for breast cancer. However, risk was significantly increased for women who consumed > or =15 g/day of alcohol (RR = 2.93, 95% CI 1.55-5.54). Age at starting drinking and frequency of consumption per week were not significantly associated with breast cancer risk. Our cohort study demonstrated that Japanese women who consume at least a moderate amount of alcohol have an increased risk of breast cancer.     

Decreased rates of advanced breast cancer due to mammography screening in The Netherlands

The effect of the implementation of the Dutch breast cancer screening programme during 1990-1997 on the incidence rates of breast cancer, particularly advanced breast cancer, was analysed according to stage at diagnosis in seven regions, where no screening took place before 1990. The Netherlands Cancer Registry provided detailed data on breast cancer incidence in 1989-1997 by tumour stage, age and region. Annual age-adjusted incidence rates of all breast cancers and advanced cancers, defined as large tumours T2+ with lymph node and/or distant metastases, were compared with rates in 1989. In general, breast cancer incidence rose strongly in the early 1990s, especially in the age category 50-69 years (estimated annual percentage change (EAPC) 4.25; 95% CI 1.70, 6.86). The increase was mainly due to the increase in small T1 cancers and ductal carcinoma in situ. However, in women aged 50-69, advanced cancer incidence rates showed a significant decline by 12.1% in 1997 compared with 1989 (EAPC -2.14, 95% CI -3.47, -0.80), followed by a breast cancer mortality reduction of similar size after approximately 2 years. We confirm that breast cancer screening initially leads to a temporary strong increase in the breast cancer incidence, which is followed by a significant decrease in advanced diseases in the women invited for screening. It is evident that breast cancer screening contributes to a reduction in advanced breast cancers and breast cancer mortality.     

Cigarette smoking,glutathione-s-transferase M1 and t1 genetic polymorphisms,and breast cancer risk (United States)

Objective: It has been suggested that functional polymorphisms in genes encoding tobacco carcinogen-metabolizing enzymes may modify the relationship between tobacco smoking and breast cancer risk. We sought to determine if there is a gene–environment interaction between GSTM1 (GSTM1A and GSTM1B), and GSTT1 genotypes and cigarette smoking in the risk of breast cancer. Methods: Cases and controls were recruited in a case–control study conducted in Connecticut from 1994 to 1998. Cases were histologically confirmed, incident breast cancer patients, and controls were randomly selected from women histologically confirmed to be without breast cancer. A total of 338 cases and 345 controls were genotyped for GSTM1 and GSTT1. Results: None of the GSTM1 genotypes, either alone or in combination with cigarette smoking, was associated with breast cancer risk. There was, however, a significantly increased risk of breast cancer among postmenopausal women with a GSTT1 null genotype (OR = 1.9, 95% CI 1.2–2.9). There were also indications of increased risk of breast cancer associated with cigarette smoking for postmenopausal women with GSTT1-null genotype, especially for those who commenced smoking before age 18 (OR = 2.9, 95% CI 1.0–8.8). Conclusion: Women with a GSTT1-null genotype may have an increased breast cancer risk, especially postmenopausal women who started smoking at younger ages.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.