Estrogen receptor-alpha polymorphism in a Taiwanese clinical breast cancer population: a case-control study

Introduction  

Receptor-mediated estrogen activation participates in the development and progression of breast cancer. Estrogen receptor (ER)-α polymorphism has been found to be associated with breast cancer and clinical features of the disease in Caucasians. Epidemiologic studies have revealed that age–incidence patterns of breast cancer in Asians differ from those in Caucasians. Genomic data for ER-α in either population is therefore of value in the clinical setting for that ethnic group.     

Risk factors for subsequent invasive breast cancer and breast cancer death after ductal carcinoma in situ: a population-based case-control study in Sweden.

In a case-control study derived from a cohort of 4661 women with a primary carcinoma in situ of the breast, we investigated age at diagnosis, mode of detection, tumor characteristics, and primary therapy, as prognostic factors for developing invasive breast cancer or dying from breast cancer. From all of the women with a primary carcinoma in situ reported to the Swedish Cancer Registry from 1960 through 1992, we selected as cases all of the women with a ductal carcinoma in situ who later died of breast cancer (n = 39) or who developed a subsequent invasive cancer in either breast (n = 118). From this cohort, we also selected controls matched to the cases by year of diagnosis and health care region. We conducted univariate and multivariate analyses to study the association between risk of invasive cancer or death and the different risk factors. Large size, diameter > or = 25 mm [odds ratio (OR), 3.5; 95% confidence interval (CI), 1.1-11.4] and multifocality (OR, 3.9; 95% CI, 1.2-12.7) increased the risk of breast cancer death in univariate analysis. Postoperative radiotherapy (OR, 0.1; 95% CI, 0.0-1.0) and mastectomy (OR, 0.1-95% CI, 0.0-0.5) lowered the risk of an ipsilateral invasive cancer in multivariate analysis. The risk pattern by treatment category differed between those who had an ipsilateral invasive cancer and those who either had a contralateral cancer or died from breast cancer. The driving forces behind local and generalized disease may differ. Because confounding by indication may influence the effects of different treatments, the results should be interpreted with caution.     

Organochlorines and breast cancer: a case-control study in Brazil.

Breast cancer is an important cause of morbidity and mortality in Brazil. Some studies have analyzed the potential role of organochlorine compounds in breast cancer etiology. These chemical compounds have been widely used in agriculture and in vector-control programs in Brazil. A case-control study was carried out in the main cancer hospital of the Instituto Nacional de Cancer in Rio de Janeiro to investigate exposure to organochlorinated pesticides as a risk factor for breast cancer. We investigated 177 cases of invasive breast cancer at the hospital, between May 1995 and July 1996, and 350 controls selected among female visitors at the same hospital. In addition to information obtained from interviews, blood samples were taken, to analyze residual amounts of organochlorine by gas chromatography using an electron capture detector. [1,1-Dichloro-2, 2-bis(p-chlorophenyl)ethylene] (DDE) was determined in sera of 457 women from a total of 493 participants who had serum samples available. Residues of hexachlorobenzene were found in 11 women only. No statistically significant association was found between breast cancer risk and serum level of DDE or history of exposure to pesticides. Serum levels of DDE (ng/ml) were similar in patients (median = 3.1, mean = 5.1) and controls (median = 3.1, mean = 4.8) (p = 0.93). The age-adjusted odds ratio of breast cancer for women in the upper quintile compared with those in the lowest quintile was 0.90 (95% confidence interval 0.47-1.73). When adjusted for other variables, the risk remained not statistically significant (upper quintile odds ratio = 0.79, 95% confidence interval 0.39-1.60). In our hands, exposure to organochlorinated pesticides measured by history or serum analysis was thus not a risk factor for breast cancer.     

Fatty-acid composition in serum phospholipids and risk of breast cancer: an incident case-control study in Sweden.

The study of the relationship between dietary intake of fatty acids and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis of possible protection of n-3 polyunsaturated fatty acids (PUFA) against breast cancer in women, we examined the fatty-acid composition of phospholipids in pre-diagnostic sera of 196 women who developed breast cancer, and of 388 controls matched for age at recruitment and duration of follow-up, in a prospective cohort study in Umea, northern Sweden. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Conditional logistic-regression models showed no significant association between n-3 PUFA and breast-cancer risk. In contrast, women in the highest quartile of stearic acid had a relative risk of 0.49 (95% confidence interval, 0.22-1.08) compared with women in the lowest quartile (trend p = 0.047), suggesting a protective role of stearic acid in breast-cancer risk. Besides stearic acid, women in the highest quartile of the 18:0/18:1 n-9c ratio had a relative risk of 0.50 (95% confidence interval, 0.23-1.10) compared with women in the lowest quartile (trend p = 0.064), suggesting a decrease in breast-cancer risk in women with low activity of the enzyme delta 9-desaturase (stearoyl CoA desaturase), which may reflect an underlying metabolic profile characterized by insulin resistance and chronic hyper-insulinemia.     

Reproductive history and risk of breast cancer: a case-control study in an unselected Swedish population

Variables in reproductive histories were studied in 179 consecutively detected, unselected breast cancer patients and age-matched controls selected from a computerized population register. The comparison between patients and controls showed no significant difference in age at meanarche, age at first birth, age at menopause or number of children. A subdivision into pre- and post-menopausal women yielded no further information. These results are at variance with most earlier reports, possible because the controls here were selected from the whole female population instead of hospitalized patients. Our data do not support the view that it is possible to define groups at high risk for breast cancer on the basis of productive histories.     

Diet and breast cancer: a case-control study in Greece

A case-control study of the role of diet in the etiology of breast cancer was conducted in Athens, Greece. There are reasons to believe that the diet of the Greek population is characterized by greater heterogeneity than that in most countries where such studies have been undertaken. The case series consisted of 120 consecutive patients with histologically confirmed breast cancer admitted to either of two teaching hospitals over a 12-month period. The controls were 120 patients admitted to a teaching hospital for trauma and orthopedic conditions during the same period. Dietary histories concerning the frequency of consumption of 120 foods and drinks were obtained by interview. Cases reported significantly less frequent consumption of vegetables as a group and, within that group, specifically of cucumber, lettuce and raw carrot. After adjustment for potential external confounding variables and for confounding between food categories, the odds ratio for persons in the highest quintile of vegetable consumers, relative to those in the lowest quintile, was 0.09 with 95% confidence limits 0.03-0.30. That is to say, the lowest quintile of vegetable consumers had about 10 times the breast cancer risk of the highest quintile. For a score based on consumption of only the 3 specified salad items the odds ratio over the extreme quartiles was 0.12 (0.05-0.32). There was no association with consumption of fats and oils, alcohol or coffee, and no significant association with any other major food category (including alcohol and coffee) after adjustment for confounding variables.     

Rauwolfia use and breast cancer: a case-control study

Breast cancer risk among 1,362 cases and 1,250 controls participating in a large multicenter screening program was examined in relation to hypertension and the use of rauwolfia derivatives. A previous diagnosis of hypertension, reported by 22% of the cases and 23% of the controls, was not associated with an increased risk of breast cancer [odds ratio (OR) = 0.9]; nor was there any excess risk for long-term hypertensives. In addition, there was no significant increase in risk associated with use of either rauwolfia derivatives (OR = 1.2), thiazide preparations (OR = 1.2), or methyldopa (OR = 1.1). However, there were significant excess risks among long-term users and those with extended intervals since first use of rauwolfia. Rauwolfia users of 10 or more years' duration or those whose initial use occurred greater than or equal to 10 years before diagnosis had risk ratios of 4.5 (95% Cl, 1.2-19.8) and 3.8 (95% Cl, 2.3-11.6), respectively. These results suggest that women exposed to long-term rauwolfia use have an elevated risk of developing breast cancer, although the results fail to support previous observations of a generalized adverse effect.     

Endocrine profile in a patient with familial breast cancer: a case-control study.

Urinary and blood hormonal profiles were studied throughout a monthly cycle in a patient with familial breast cancer. Two comparison cohorts (one high-risk and one low-risk) were studied concurrently. Findings disclosed that our breast cancer-affected patient showed a distinctive hormonal pattern characterized by significant elevation throughout the cycle of plasma estrone, estradiol, and prolactin. Save for a depression in plasma FSH in the early follicular phase, this hormone, as wells as LH and progesterone patterns in our patient, were similar to the comparison cohorts. Urinary estrone and estradiol patterns in our patient were elevated early in the follicular phase. Our patient also showed a depression in urinary estrone, estradiol, and estriol following ovulation, which persisted throughout the luteal phase. Blood and urinary hormone patterns in the high-risk cohort were not demonstrably different from the low-risk cohort, with the exception of plasma prolactin. The results on the latter hormone showed an unexpected significant depression throughout most of the menstrual cycle in this low-risk cohort. We conclude that estrone and estradiol elevations, as clearly evidenced in our breast-cancer-affected patient, may provide clues that ultimately might be used as an etiologic discriminant for breast cancer risk and which may also play a pathogenic role in this disease. Since this involved a single patient, our conclusions must be interpreted cautiously.     

Aspirin and risk for gastric cancer: a population-based case-control study in Sweden

While aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) are associated with gastric mucosal damage, they might reduce the risk for gastric cancer. In a population-based case-control study in 5 Swedish counties, we interviewed 567 incident cases of gastric cancer and 1165 controls about their use of pain relievers. The cases were uniformly classified to subsite (cardia/non-cardia) and histological type and information collected on other known risk factors for gastric cancer. Helicobacter pylori serology was tested in a subset of 542 individuals. Users of aspirin had a moderately reduced risk of gastric cancer compared to never users; odds ratio (OR) adjusted for age, gender and socioeconomic status was 0.7 (95% CI = 0.6-1.0). Gastric cancer risk fell with increasing frequency of aspirin use (P for trend = 0.02). The risk reduction was apparent for both cardia and non-cardia tumours but was uncertain for the diffuse histologic type. No clear association was observed between gastric cancer risk and non-aspirin NSAIDs or other studied pain relievers. Our finding lends support to the hypothesis that use of aspirin reduces the risk for gastric cancer.     

Common ERBB2 polymorphisms and risk of breast cancer in a white British population: a case-control study

IntroductionAbout two-thirds of the excess familial risk associated with breast cancer is still unaccounted for and may be explained by multiple weakly predisposing alleles. A gene thought to be involved in low-level predisposition to the disease is ERBB2 (HER2). This gene is involved in cell division, differentiation, and apoptosis and is frequently amplified in breast tumours. Its amplification correlates with poor prognosis. Moreover, the coding polymorphism I655V has previously been associated with an increased risk of breast cancer.MethodsWe aimed to determine if common polymorphisms (frequency ≥ 5%) in ERBB2 were associated with breast cancer risk in a white British population. Five single-nucleotide polymorphisms (SNPs) were selected for study: SNP 1 near the promoter, SNP 2 in intron 1, SNP 3 in intron 4, SNP 4 in exon 17 (I655V), and SNP 5 in exon 27 (A1170P). We tested their association with breast cancer in a large case–control study (n = 2192 cases and 2257 controls).ResultsThere were no differences in genotype frequencies between cases and controls for any of the SNPs examined. To investigate the possibility that a common polymorphism not included in our study might be involved in breast cancer predisposition, we also constructed multilocus haplotypes. Our set of SNPs generated all existing (n = 6) common haplotypes and no differences were seen in haplotype frequencies between cases and controls (P = 0.44).ConclusionsIn our population, common ERBB2 polymorphisms are not involved in predisposition to breast cancer.     

Risk factors for breast cancer in Iran: a case-control study

Background  

Iranian breast cancer patients are relatively younger than their Western counterparts. The objective of the present study was to investigate risk factors for breast cancer in Iranian women.     

Lactation and breast cancer risk: a case-control study in Connecticut

In this report, we examined the relationship between lactation and breast cancer risk, in a case-control study of breast cancer, conducted in Connecticut between 1994 and 1998. Included were 608 incident breast cancer cases and 609 age frequency matched controls, aged 30-80 years old. Cases and controls were interviewed by trained study interviewers, using a standardized, structured questionnaire, to obtain information on lactation and other major risk factors. Parous women who reported ever lactation had a borderline significantly reduced risk of breast cancer (OR = 0.83, 95% CI, 0.63-1.09). An OR of 0.53 (95% CI, 0.27-1.04) was observed in those having breastfed more than 3 children compared to those who never lactated. Women having breastfed their first child for more than 13 months had an OR of 0.47 (95% CI, 0.23-0.94) compared to those who never breastfed. Lifetime duration of lactation also showed a risk reduction while none of the ORs were statistically significant. Further stratification by menopausal status showed a risk reduction related to lactation for both pre- and postmenopausal women, while the relationship is less consistent for the latter. These results support an inverse association between breastfeeding and breast cancer risk.     

Benign breast disease and breast cancer: a case-control study in a cohort in Italy

Sixty-two cases of invasive breast cancer were identified in a large cohort of women previously treated for biopsy-proven benign breast disease (BBD) at the Breast Unit of CSPO, in Florence, along with a group of 315 controls, strictly matched by age and year of diagnosis. A pathologist reviewed and reclassified all the original BBD slides according to recently proposed criteria (no evidence of epithelial proliferation, epithelial proliferation without or with atypia). Information about potential confounding factors was collected during personal interviews. In comparison to the women with "non-proliferative" BBD, women classified as having "proliferative disease without atypia" showed a weak and non-significant increase in risk (OR 1.3; 95% CI: 0.5-3.5). In contrast, women with "atypical hyperplasia" were at very high risk of developing breast cancer (OR 13.0; 95% CI: 4.1-41.7). When planning mammography screening or other large-scale early-diagnosis programmes for breast cancer in the general female population, follow-up of high-risk subgroups of BBD patients should be considered.     

Coffee and methylxanthines and breast cancer: a case-control study

A dietary case-control study based on 818 newly diagnosed breast cancer (BC) patients was conducted in Israel between 1975 and 1978. The role of coffee and total methylxanthine intake from coffee, tea, cola, chocolate, and cocoa drinks was evaluated in the BC patients as compared to that in two matched control populations [surgical controls (SC) and neighborhood controls (NC)]. Because it has been suggested that caffeine enhances mammary carcinogenesis in rats fed high polyunsaturated fat diets, analysis was done also in relation to fat consumption. When comparison was done to both matched control groups, a nonsignificant negative association was found between consumption of cups of coffee and BC (odds ratios of greater than or equal to 4 cups of coffee/day vs. less than or equal to 1 per week = 0.6 for BC/NC and 0.7 for BC/SC). This association was observed in all 3 ethnic subgroups studied. The pattern was stronger among the high-fat consumers after controlling for several hormonal confounding factors (two-tailed P-value for linear trend = 0.06 for SC and P = 0.05 for NC). In addition, when the consumption of methylxanthine of BC patients was compared to that of benign breast patients, adjusted by age and ethnic group, a diminished risk was found (odds ratio for BC of the highest level of methylxanthine vs. lowest level = 0.59).     

Endometrial cancer following treatment for breast cancer: a case-control study in Denmark

To evaluate the risk of endometrial cancer subsequent to breast cancer, a case-control study was carried out in Denmark. Between 1943-1977, 115 cases of histologically confirmed endometrial carcinoma developed more than 3 months after the diagnosis of a primary breast cancer in 51,638 women. A total of 235 breast cancer patients with no second primary cancer were matched to the cases on age, calendar year of diagnosis, and survival with an intact uterus. Identification of cases and controls relied upon records available in the Danish Cancer Registry. Information on risk factors and reproductive histories was abstracted from hospital records. Increased relative risks (RR) for endometrial cancer were associated with menopausal oestrogen use (RR = 4.9), nulliparity (RR = 2.1), late age at natural menopause (RR = 2.9), and pelvic irradiation (RR = 1.4). No association was apparent for drugs used to treat breast cancer. This study indicates that breast and endometrial cancer share several common aetiologic factors and that studies of second primary cancers have the potential to provide information on risk factors other than those associated with therapy.     

Nutrients and gastric cancer risk. A population-based case-control study in Sweden

A population-based case-control study of gastric cancer was conducted in areas with contrasting incidence rates in Sweden. Face-to-face interviews were carried out with 338 (74.1 %) of all eligible cases and 679 (77.3%) of the selected controls. Consumption of selected nutrients during adolescence and 20 years prior to interview was estimated, together with life-time intake of vitamin supplements. Ascorbic acid and β-carotene had an unequivocal protective effect, but α-tocopherol and nitrate were also negatively associated with gastric-cancer risk. In a multivariate analysis including all of these factors, only ascorbic acid remained a significant protective factor. The only macronutrient positively associated with the risk of gastric cancer was fat: intake 20 years prior to interview, but not during adolescence, was found to have a significant impact. Supplementation with vitamins almost halved the risk after adjustment for dietary intake of the corresponding vitamins. While the protective effect of vitamin C and β-carotene could conceivably be ascribed to other agents in the diet, the strong negative association between supplementation with vitamin C and risk of gastric cancer supports the hypothesis of a protective role of this anti-oxidant.     

Risk for endometrial cancer following breast cancer: a prospective study in Sweden

The risk for endometrial cancer among women with breast cancer might increase following use of tamoxifen, recently classified as a carcinogen of the human endometrium. However, the strength of the association remains uncertain and it is unknown whether use of this drug - widely prescribed in Sweden since the mid-1980s - has had any measurable effect at the population level. We analyzed all cases of breast cancer (n = 131,614) detected in the nationwide Swedish Cancer Registry in 1958-93. Incident cases of endometrial cancer during follow-up were identified also through the Cancer Registry. Standardized incidence ratios (SIR) and their 95 percent confidence intervals(CI) were computed by use of nationwide rates of endometrial cancer, adjusted for age and calendar year. During follow-up of up to 35 years of the breast cancer cohort, 803 incident endometrial cancers were identified, yielding an overall SIR of 1.58 (CI = 1.47-1.70). In univariate analyses, there was no increase in SIR in recent years. However, the excess risk increased linearly with increasing age at breast cancer diagnosis (P trend < 0.0001) and decreased markedly with longer follow-up (P trend < 0.0001). A multivariate regression analysis, with adjustment for age and year of follow-up, revealed no increased risk for subsequent endometrial cancer among breast cancer cases diagnosed more recently (P trend = 0.19); compared with the period 1958-63,the risk estimate in the last time period (1989-93) was 0.72 (CI =0.51-1.01). We conclude that the risk for endometrial cancer following breast cancer has not increased over time in Sweden. This revised version was published online in July 2006 with corrections to the Cover Date.     

Fatty fish consumption lowers the risk of endometrial cancer: a nationwide case-control study in Sweden.

The consumption of fatty fish, which contains large amounts of omega-3 fatty acids, may lower the risk of hormone-responsive cancers. Our aim was to study the association of fish consumption and endometrial cancer risk in Sweden, a country with a wide range of high fatty fish consumption. Using data from a large, nationwide case-control study (709 cases and 2888 controls), we analyzed consumption of both fatty (e.g., salmon and herring) and lean (e.g., cod and flounder) fish in relation to endometrial cancer risk, adjusting estimates for a wide range of potentially confounding variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models fit by maximum likelihood methods. Consumption of fatty fish was inversely associated with endometrial cancer risk. The multivariate OR for women in the highest quartile level (median, 2.0 servings per week), compared to women with in the lowest (median, 0.2 servings per week), was 0.6 (95% CI, 0.5-0.8; P for trend, 0.0002). The corresponding OR for women in the highest quartile level of lean fish (median, 2.5 servings per week), compared to women in the lowest (median, 0.6 servings per week), was 1.0 (95% CI, 0.8-1.3; P-value for trend, 0.72). Total fish consumption was inversely associated with risk, although weakly. Our results suggest that the consumption of fatty fish, but not other types of fish, may decrease the risk of endometrial cancer.     

Familiality of breast cancer and socioeconomic status in blacks

Familial patterns of the occurrence of breast cancer were studied in a population-based case-control series of black women from the Cancer and Steroid Hormone study. The risks of breast cancer among relatives of breast cancer cases were compared to those of controls who were matched for age and locale. Using the term "proband" to indicate either case or control status, significant predictors of risk to the relatives of probands included case/control status of the proband and the number of years of education completed by the proband. Genetic segregation analysis of the case families using external risks generated from SEER data indicated that the familial aggregation was consistent with Mendelian recessive transmission of a single major gene. The use of internally estimated risks, which are much less stable than the SEER risks, no longer permitted discrimination among the major locus models examined. To avoid possible reporting bias, we also performed segregation analysis on families of probands who had completed at least 12 years of education. The results from this analysis reflected the results from the entire data.     

Abortions and breast cancer: record-based case-control study

The original article to which this Erratum refers was published in International Journal of Cancer (2003) 108(2) 269–276