A population-based cohort study of HRT use and breast cancer in southern Sweden

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93-1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02-1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86-1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09-1.64) compared with never users (SIR = 1.07, 95% CI 0.96-1.19). Breast cancer increased with increasing duration of use and for 48-120 months use the SIR was 1.92 (95% CI 1.32-2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use.     

Reproductive factors and risk of oesophageal cancer, a population-based nested case-control study in Sweden

Background:

The role of sex hormonal influence in explaining the strong male predominance in oesophageal adenocarcinoma (EA) needs attention.

Methods:

A nation-wide nested case–control study was initiated from the Swedish Multi-Generation Register with subjects born since 1932. The study exposures were the number of children and age at having the first child. Cases of EA, gastroesophageal junctional adenocarcinoma (EJA), and oesophageal squamous cell carcinoma (SCC) were identified. Ten age- and sex-matched controls were randomly selected for each case. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results:

In women, 115 EA, 246 EJA, and 363 SCC were identified. Comparing parous with non-parous women, a decreased risk of EA was indicated (OR=0.66, 95% CI 0.38–1.14), which became statistically significant when EA and EJA were combined (OR=0.73, 95% CI 0.53–0.99). All these associations were, however, at least as strong in men. Age at first birth did not show significant risk in women, but showed risk in men. In addition, the results were similar for SCC in both sexes.

Conclusion:

These findings indicate that associations between the reproductive factors parity and age at first birth, and risk of EA might not be explained by sex hormonal influence.     

Risk factors for breast cancer in Turkish women: a hospital-based case-control study

The aim of this study was to investigate the association between risk factors and breast cancer in Turkish women. In a hospital-based case-control study in Istanbul, 405 patients with histologically confirmed breast cancer were compared with 1050 controls, who were admitted to different departments of the same hospital. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor were obtained from logistic regression analyses. Risk factors for breast cancer were found to be early menarche age (OR 3.87, 95% CI 2.46-6.08), use of alcohol (OR 3.87, 95% CI 1.79-8.37), history of diabetes (OR 3.31, 95% CI 2.36-4.64) or hypertension (OR 3.44, 95% CI 2.07-5.71), oral contraceptive use (OR 1.98, 95% CI 1.38-2.85) and hormone replacement therapy (HRT) use (OR 1.94, 95% CI 1.15-3.29). The findings of the present study indicated that history of diabetes or hypertension, use of alcohol, oral contraceptive and HRT, never having breastfed and delayed age at first birth associated with changing of lifestyle led to an increased risk of breast cancer in Turkish women.     

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

Family history of breast cancer and short-term effects of childbirths on breast cancer risk

The long-term protective effect of a pregnancy on breast cancer risk is preceded by a short-term adverse effect, possibly reflecting a promoting effect of pregnancy hormones. In the present study, we explore whether a family history of breast cancer modifies time-related effects of pregnancies, with special emphasis on the transient increase in risk of breast cancer shortly after birth. Our study cohort comprises 1,067,289 Norwegian women aged 20-74 years. The mean follow-up time was 18 years. Incidence rate ratios were estimated by Poisson regression analyses of person-years at risk. Of the 7,377 women diagnosed with breast cancer during follow-up, a total of 828 (11%) had a mother or a sister with breast cancer diagnosis. Women with a family history of breast cancer had a 2-3-fold higher risk of breast cancer than did women without any affected family member, highest for those with a relative diagnosed before they were 50 years. Similar to women without a familial excess risk, increasing parity was associated with an overall protective effect among women with a familial predisposition, regardless of age at diagnosis of the relative. Whereas women with no familial excess risk experienced a transient increase in risk mainly after late age births, women with a family history of breast cancer experienced an adverse effect of pregnancies also at younger ages. The present results give further support to the hypothesis that the adverse effect of a term birth can be explained by a promoting effect of pregnancy hormones.     

A cohort study of reproductive and hormonal factors and renal cell cancer risk in women

We examined the association of reproductive and hormonal factors with renal cell cancer risk in a cohort study of 89 835 Canadian women. Compared with nulliparous women, parous women were at increased risk (hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.02-3.09), and there was a significant gradient of risk with increasing levels of parity: relative to nulliparous women, women who had > or =5 pregnancies lasting 4 months or more had a 2.4-fold risk (HR=2.41, 95% CI=1.27-4.59, P for trend 0.01). Ever use of oral contraceptives was associated with a modest reduction in risk. No associations were observed for age at first live birth or use of hormone replacement therapy. The present study provides evidence that high parity may be associated with increased risk of renal cell cancer, and that oral contraceptive use may be associated with reduced risk.     

Prognostic significance of etiological risk factors in early breast cancer

Several risk factors for the etiology of breastcancer have also been correlated with the prognosisof breast cancer. However, the published studies haveyielded conflicting results.Women under 71 years of age with stageI, II, or III breast cancer were eligiblefor inclusion in a clinical study. 866 patientswith breast cancer entered the study, of whom463 had positive lymph nodes.Survival was analysed using Cox's proportional hazards model.Age at menarche, parity, age at menopause andfamily history were not consistently related to survival.Young age at first full-term pregnancy was relatedto decreased survival (adjusted relative risk (RR): 1.69,95% confidence intervals (95% CI): 1.04–2.68), but itcannot be excluded that this result was dueto chance alone. Use of oral contraceptives wasnot correlated with survival (RR: 1.10, 95% CI:0.80–1.51) nor was family history (RR: 0.93, 95%CI: 0.66–1.30).This study provided little support for the hypothesisthat risk factors for breast cancer are relatedto survival.     

Young women with family history of breast cancer and their risk factors for benign breast disease

BACKGROUND:

Breast cancer (BC) patients wonder how their daughters might reduce their risk. The authors investigated childhood/adolescent risk factors for benign breast disease (BBD), a well‐documented risk factor for BC, among girls with a family history.

METHODS:

GUTS (the Growing Up Today Study) includes females, aged 9 to 15 years in 1996, who completed annual questionnaires during 1996 to 2001, then in 2003, 2005, and 2007. Participants provided information regarding alcohol, menarche, height, and body mass index (BMI; kg/m²). Peak height growth velocity (PHV; in./y) was estimated from longitudinal heights. On 2005‐2007 surveys, 6888 women (18‐27 years old) reported whether they were diagnosed with biopsy‐confirmed BBD (n = 67 cases); 6741 women (noncases) reported no BBD. Participants' mothers reported their own biopsy‐confirmed BBD and BC, and BC in their sisters and mothers. Stratified by family history, logistic models investigated BBD risk factors.

RESULTS:

Young women whose mothers or aunts had BC were more likely to be diagnosed with BBD (odds ratio [OR], 2.34; P = .01), as were those with maternal BBD (OR, 1.59; P = .095). Adolescents with BC family history (mother, aunt, grandmother) who consumed alcohol (7 drinks/wk) doubled their BBD risk (OR, 2.28; P = .01), similar to those with maternal BBD (OR, 1.96; P = .02). Girls whose mother or aunt had BC saw their BBD risk elevated with higher PHV (OR, 1.82 [inch/yr]; P = .05). Among girls with no family history, BBD risk appeared to be related to other factors: childhood BMI, adolescent waist circumference, and adult height.

CONCLUSIONS:

Adolescents with family history may reduce their risk by avoiding alcohol. Separate risk factors were observed among girls with family history versus girls with no family history, possibly reflecting different causes of BC. Cancer 2011;. © 2011 American Cancer Society.     

Lifestyle and cancer incidence and mortality risk depending on family history of cancer in two prospective cohorts

The extent to which a favorable lifestyle may lower cancer risk in subjects with a family history of cancer is unknown. We conducted a prospective study in two Swedish cohorts, the Malmö Diet and Cancer Study (MDCS; n = 25,604) and the Malmö Preventive Project (MPP; n = 16,216). The association between a favorable lifestyle (based on nonsmoking, normal weight, absence of excessive drinking, regular physical activity and healthy diet) and cancer incidence and mortality risk was assessed using Cox regression stratified by family history of cancer (all types). A favorable lifestyle was associated with a 22% (95% confidence interval [CI]: 18–26%) and 40% (95% CI: 36–44%) lower risk of cancer incidence and mortality, respectively, compared to an unfavorable lifestyle. No significant effect modification by family history was observed but there was a null association between lifestyle and cancer incidence among subjects with two or more affected first-degree relatives. The observed relative risk estimates comparing an unfavorable with a favorable lifestyle corresponded to standardized 10-year cancer incidence rates of 11.2 vs. 9.5% in the MDCS, and 4.4 vs. 3.2% in the MPP, and a reduction in 20-year cancer mortality rate from 11.7% to 7.4% in the MDCS and 6.7% to 3.9% in the MPP. Improved adherence to cancer prevention recommendations may reduce cancer incidence and mortality risk in the general population, however, further studies are needed to assess the impact of lifestyle on cancer incidence among subjects with strong familial or polygenic risk for specific cancers.     

Family history and breast cancer tumour characteristics in screened women

Women with a family history of breast cancer have an increased risk of the disease. However, since they tend to experience greater surveillance for the disease, their breast cancers may be detected at an earlier stage, thus making it difficult to assess reliably whether tumour characteristics vary by family history. Information on 9,731 Million Women Study participants with screen-detected breast cancer, diagnosed in 1996-2003, and 37,983 matched controls, who also attended routine screening but were not diagnosed with breast cancer, was used to estimate adjusted relative risks (RRs) of screen-detected breast cancer in women with a family history of the disease. Women with a family history of breast cancer had an increased risk of screen-detected breast cancer (RR 1.57; 95% CI:1.47-1.68) compared with those without such a family history. The RRs were 1.58 (1.46-1.71) and 1.55 (1.34-1.80) for invasive and in situ breast cancer; 1.63 (1.49-1.79) and 1.55 (1.32-1.83) for node-negative and node-positive disease; and 1.56 (1.42-1.70), 1.75 (1.39-2.21) and 1.71 (1.28-2.29) for ductal, lobular and tubular cancers. There was no significant difference in the RR of screen-detected breast cancer associated with a family history of the disease according to invasiveness, size, nodal status, malignancy grade or morphological type of the breast cancer.     

Breast cancer risk factors and age at diagnosis: an Icelandic cohort study

An increasing number of studies indicates that the strength and even direction of association between breast cancer and established risk factors differ according to the woman's age when she develops the disease. This was studied in the setting of a population based cancer registry using a databank with information on age at menarche, parity, age at first birth, oral contraceptive (OC) use, lactation, height and weight. From a cohort of 80.219 women attending population-based cervical and breast cancer screening in Iceland, 1120 cases were identified, aged 26-90 years at diagnosis and 10,537 controls, individually matched to the cases on birth year and age when attending. Information given at last visit before diagnosis was used in the analysis, applying conditional logistic regression. Odds ratios and statistical strength of relationships varied according to age at diagnosis for age at first birth, number of births, duration of lactation, height and weight. The decreased risk associated with young age at first birth and increasing duration of breast feeding became less pronounced with advancing age at diagnosis. A reduced risk associated with an increasing number of births was not detected in women diagnosed under the age of 40. An increased risk associated with giving first birth after 30 years of age was mainly detected in women who had only given 1 birth and were diagnosed under the age of 40 (OR = 7.06 95% CI = 2.16-23.01). A positive association with height and especially with weight was confined to women diagnosed after the age of 55. The results confirm that age at diagnosis should be taken into account when studying the effects of breast cancer risk factors.     

Incidence and mortality in epithelial ovarian cancer by family history of any cancer

BACKGROUND:

Practically all data on familial risk in ovarian and other cancers are based on incident cancer, whereas familiality in cancer mortality is largely unknown. If fatal forms of cancer are a highly familial subtype, then familial risk for mortality may exceed that of incidence, which is relevant for clinical decision making and counseling.

METHODS:

Ovarian cancer patients in the nationwide Swedish Family Cancer Database were classified according to fatal and nonfatal (incident) family history. Familial risks for incident and fatal ovarian cancer were calculated for offspring based on their parental or sibling family history of any cancer using standardized incidence ratios (SIRs) for incidence and standardized mortality ratios (SMRs) for mortality. Offspring without family history were referents.

RESULTS:

The database included 24,757 mothers and 8138 daughters with ovarian cancer. When a mother had ovarian cancer, the SIR for incident ovarian cancer in daughters was 2.69, and when a sister had ovarian cancer it was 3.49. The SMRs for fatal cancer by fatal cancer in probands were 3.39 and 5.80, respectively. For fatal serous cancers among siblings, the SMR was 6.16, compared with 10.01 for the endometrioid type. Ovarian cancer was associated with maternal (SIR, 1.22; SMR, 1.56) and sororal breast cancer (SIR, 1.27). Another discordant association was between ovarian and paternal prostate cancer (SIR, 1.12; SMR, 1.66).

CONCLUSIONS:

Fatal familial risks were higher for concordant ovarian, ovarian‐breast, and ovarian‐prostate cancers than the corresponding incident risks. This may suggest that highly fatal subtypes exist for these cancers, calling for genetic dissection. Cancer 2011. © 2011 American Cancer Society.     

Correlations between family history and cancer characteristics in 2256 breast cancer patients

A comparison of 692 early invasive breast cancer with, and 1564 without, a family history of breast cancer showed that the former were younger at diagnosis (P=0.002), had smaller tumours (P=0.012), were more frequently oestrogen receptor positive (P=0.006) and diagnosed preclinically (P<0.001).     

Influence of young age at diagnosis and family history of breast or ovarian cancer on breast cancer outcomes in a population-based cohort study

PURPOSE: The objective of this study was to examine the association of: (i) diagnosis at age 相似文献   

Menstrual and reproductive factors and risk of gastric cancer: a Norwegian cohort study

Objective:To explore relations between menstrual and reproductive factors and incidence of gastric cancer in a cohort study of 63,090 Norwegian women, followed over a period of 29 years. Methods:Associations with potential risk factors were evaluated by Poisson regression analysis, considering 572 cases of gastric cancer diagnosed in women aged less than 80 years. Results:Age at menarche showed a moderate inverse association with overall risk of gastric cancer (incidence rate ratio 0.93 per year; 95% confidence interval 0.88–1.00). No association could be established with age at menopause. Among women aged less than 50 years, an old age at first delivery was related to an increased risk, mainly of cancer of the distal part of the stomach. In multiparous women aged 50 years or more, relations with childbearing history differed significantly between subsites. Women with many pregnancies over a short period of time had an increased risk of cancer of the proximal part of the stomach. In the distal part, pregnancies over a long period seemed to confer a higher risk. Conclusions:Relations between reproductive factors and risk of gastric cancer should be assessed separately for pre- and postmenopausal women and for subsites.     

Reproductive factors and family history of breast cancer in relation to plasma prolactin levels in premenopausal and postmenopausal women

Many reproductive factors are associated with breast cancer risk, potentially through a hormonal pathway. The peptide hormone prolactin is essential in mammary development and lactation and may be a link between risk factors and breast cancer. While higher prolactin levels are associated with increased breast cancer risk, few determinants of prolactin levels are known. We conducted a cross-sectional analysis among 1,089 premenopausal and 1,311 postmenopausal women within the Nurses' Health Study (NHS) and the NHS II to examine the associations of reproductive factors, benign breast disease and family history of breast cancer with plasma prolactin levels. Parous women had significantly lower prolactin levels than nulliparous women (parous vs. nulliparous multivariate-adjusted geometric means = 14.1 ng/mL vs. 16.6 ng/mL, p<0.001 for premenopausal and 9.1 vs. 10.1, p=0.04 for postmenopausal women), although levels did not decrease with increasing number of children for either premenopausal (p-trend = 0.23) or postmenopausal (p-trend = 0.07) parous women. Age at first birth was not associated with prolactin levels. The reduction in prolactin levels among parous premenopausal women appeared to attenuate with increasing time since first birth, but the trend was not statistically significant (p-trend = 0.12). Age at menarche, duration of lactation and benign breast disease were not associated with prolactin levels. Family history of breast cancer was associated with significantly higher prolactin levels when compared with no family history among premenopausal (15.9 ng/mL vs. 14.3 ng/mL, p=0.04) but not postmenopausal (p=0.73) women. In conclusion, the associations of parity and family history with breast cancer risk may be mediated, at least in part, by prolactin levels.     

Family history of breast cancer,age and benign breast disease

A major risk factor for breast cancer is having a first-degree family history of the disease. Benign breast disease (BBD), particularly atypical hyperplasia, is also associated with an increased risk of breast cancer. However, the relationship between family history of breast cancer and BBD is unclear. From 1989 through 1997, 80,995 participants in the Nurses' Health Study II were followed; 16,849 reported a first diagnosis of BBD. Pathology slides were reviewed for 1,465 women who reported having a tissue biopsy, and these were classified as nonproliferative BBD, proliferative BBD without atypia or atypical hyperplasia. Women with a family history of breast cancer were more likely to report a physician diagnosis of BBD [rate ratio (RR) = 1.38, 95% confidence interval (CI) 1.29-1.46]. The magnitude of this association declined with age from RR = 1.96 (95% CI 1.55-2.47) at 25-29 years to RR = 1.20 (95% CI 0.95-1.52) at age 45-50 years. Among women with proliferative disease, those with a family history of breast cancer were almost 3 times as likely to have atypia (prevalence odds ratio = 2.72, 95% CI 1.23-5.89) than those with no family history. In conclusion, women with a family history of breast cancer appear to be at increased risk of being diagnosed with BBD, in particular the high-risk types of BBD associated with a greatly increased risk of breast cancer. This link adds weight to the belief that BBD with atypia is a precursor or marker lesion for breast cancer.     

Consistency of self-reported first-degree family history of cancer in a population-based study

The aim of this study was to assess the prevalence and consistency of self-reported family history of cancer among first-degree relatives (FDR) in a population-based study. Women at primary care units (PCU) were submitted to a questionnaire about cancer family history. Consistency of the report was determined by comparing self-reported history at the PCU to data from subsequent genetic evaluations and/or cancer confirmatory documents. Consistency in relation to degree of education, reported tumor type and reported age at cancer diagnosis in FDR was assessed. In 8,881 women interviewed, the prevalence of cancer in an FDR was 25.14% (CI 95%: 24.14; 25.94). Mean age was 40.29 years and most (70.26%) had ≤8 years of education. There was a good agreement of self-reported cancer history at the PCU and in subsequent genetic evaluations [Kappa coefficient = 0.76 (P < 0.05)]. Inconsistencies were not related to low literacy (χ ² = 2.027; P = 0.363). Consistency of the reported information for cancer status, cancer type and age of onset was 92.59%, 85.33% and 92.64%, respectively. The prevalence of cancer history in an FDR was similar to previous reports in other populations. Consistency and reliability of the self-reported information was high, regardless of educational level.     

Grand multiparity and the risk of breast cancer: population-based study in Finland

Objectives: The significance of reproductive factors on breast cancer risk has so far been characterized in populations with 5-paras as the highest category of parity. We extended these studies to a nationwide cohort of women with at least five births (grand multiparas = GM) by assessing the significance of parity, age at first birth, and average birth interval to the risk of breast cancer. Methods: The study cohort obtained from the Population Register of Finland comprised 86,978 GM-women; the incidence of cancer cases was obtained from the populated-based Finnish Cancer Registry. During a follow-up of about 2 million person-years, 1508 breast cancers were obtained. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cases by the number expected on the basis of national rates. Results: In the GM cohort the incidence of breast cancer was low (SIR 0.55, 95% confidence interval 0.52–0.58). The relative risk decreased significantly from 5-paras (SIR 0.60, adjusted for the other study variables) to 8-paras (SIR 0.40). The increase in the age at first birth from less than 20 years to 30+ years nearly doubled the risk (SIR from 0.40 to 0.73). Parity was a significant risk determinant only in ductal cancer, while shortening the birth interval was protective only in lobular cancer. The incidence of advanced breast cancer among GM-women exceeded the population rate in premenopausal women and in women with first birth at the age of 30 years or more. Conclusions: Our study demonstrated that young age at first birth and increasing number of births were independent and powerful protective factors from the fifth child onwards, while birth interval was weak in this respect. The tumor morphology and the clinical advancement of malignancy modified the dependence of breast cancer risk on reproductive variables.