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.     

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.     

Risk factors for breast cancer: A case-control study of screen-detected breast cancer in Miyagi Prefecture, Japan

We examined the associations between reproductive factors and the risk of breast cancer on the basis of information from a total of 201,363 breast cancer screening program participants in Miyagi Prefecture, Japan, during 1987-1991. A case-control study method was applied on analysis. Data on 204 breast cancer cases identified and 810 screening year-, age- and screening area-matched normal controls were extracted. After adjustment for potential confounders, a trend of decreasing risk of breast cancer with increasing number of parity was observed (p for trend=0.03). Among parous women, lactation for the last child decreased the risk of breast cancer (odds ratio (OR) = 0.61, 95% confidence interval (95% CI) 0.39–0.94). These findings were consistent with those in clinical breast cancer reported previously. When cases were divided into two age groups, younger ( 49 y.o.) and older (50 y.o. ), family history of breast cancer among mother and sisters (OR=3.51, 95% CI 1.05–11.80), and lactation for the last child (OR=0.46, 95% CI 0.25–0.84) were associated with younger age breast cancer, whereas number of parity was associated with older age breast cancer (p for trend=0.03). The results by age group suggest that different mechanisms may exist in breast cancer developing at early and late onsets.     

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.     

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.     

Birth intervals and breast cancer risk

Background:

The interval between successive births (birth interval) may affect breast cancer risk, whereas interval from last birth to cancer onset may modify its behaviour.

Methods:

The study cohort consisted of 29 488 Finnish grand multiparous (GM) women, including 628 women with breast cancer. Conditional logistic regression for case–control design nested within the cohort was used to estimate proportional hazards (referred as relative risks, RR). Age at first birth and parity were co-variables.

Results:

Short interval (<1 year) between first and second birth increased the risk of advanced ductal breast cancer at ages < 50 years (RR=5.29; 95% CI 2.00–14.0) as compared to interval 3+ years. The risk of advanced ductal cancer was also large (RR = 4.00; 95% CI 1.19–13.4) shortly (<3 years) after last birth as compared with the period 15+ years.

Conclusions:

Short birth interval-associated excess breast cancer risk may be related to stimulatory effects of female steroid hormones produced during two closely connected pregnancies, or defective breast maturation owing to failures in breastfeeding.     

A cohort study of reproductive factors and family history of breast cancer in southern Sweden

Background. Studies have been contradictory regarding the hypothesis that reproductive risk factors of breast cancer as parity and age at first full-term pregnancy (AFFP) operate differently in women with and without a family history of breast cancer. Methods. The overall tumour incidence and breast cancer incidence related to fertility factors were followed in a population based cohort of 29,508 women aged 25–65 when interviewed between 1990 and 1992 in south Sweden. At the end of the follow up in December 1999, the cohort constituted 226,611 person years. The risk of breast cancer in relation to reproductive factors were studied in women with at least one first degree relative with breast cancer and compared with women without a family history. Findings. A total of 1145 malignant tumours were seen and 1166.6 were expected (SIR = 0.98, 95% CI = 0.93–1.04). Slightly more breast cancer cases were seen 434 than expected 387.69 (SIR = 1.12, 95% CI = 1.02–1.23). A family history of breast cancer among a first degree relative was present in 1615 women. Forty-five breast cancers were seen among these women while 24.27 was expectecd (SIR = 1.85, 95% CI = 1.35–2.48). Nulliparous women with a family history of breast cancer had a higher risk of breast cancer, SIR = 1.76, 95% CI = 0.64–3.82, compared with nulliparous women without a family history, SIR = 1.13, 95% CI 0.99–1.29. Similarly women with parity 1–2 with a family history had a higher SIR = 1.81, 95% CI = 1.16–2.69 compared with women without a family history having 1–2 children, SIR = 1.13, 95% CI = 0.99–1.29. In women with 3 children those with a family history continued to have a high SIR = 1.98, 95% CI = 1.11–3.27 compared with women without a family history SIR = 0.90, 95% CI = 0.73–1.09. An early full-term pregnancy was protective in both groups. A higher risk than nulliparous women were seen after age 25 in the family history group and after age 30 in the sporadic cancer group. Interpretation. Women with a first degree family history of breast cancer do not experience the same protection from a high number of pregnancies as women without a family history. However, an early first full-term pregnancy seems to offer a substantial protection in the family history group if undertaken before age 20. This suggest that reproductive factors tend to operate differently in the two groups of women.     

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

In order to thoroughly analyze risk factors of breast cancer (BC) in premenopausal Uruguayan women, a case-control study was carried out at the Pereira Rossell Women's Hospital, Montevideo, where 253 incident BC cases and 497 frequency-matched healthy controls were interviewed on menstrual and reproductive story, were administered a short food frequency questionnaire and undertook a series of body measurements necessary to calculate body composition and somatotype. Odds ratio (OR) coefficients were taken as estimates of relative risk derived from unconditional logistic regression. Among the classical risk factors, only the family history of BC in first degree relatives was significantly associated with risk of premenopausal BC (OR=2.20, 95% CI 1.33-3.62). Interestingly, this risk factor was found to be stronger in women of ages >40 (OR=4.05, 95% CI 2.10-7.81), late menarche (OR= 2.39, 95% CI 1.18-4.85), early age for their first delivery (OR=3.02, 95% CI 1.26-7.22), short time between menarche and first delivery (OR=3.22, 95% CI 1.29-8.07), and with high parity (OR=4.10, 95% CI 1.79-9.36), although heterogeneity was detected only for age and parity. High consumption of red meat was positively associated with the disease risk (OR=2.20, 95% CI 1.35-3.60), in the same way as fried foods (OR=1.79, 95% CI 1.12-2.84). Conversely, a high intake of plant foods displayed a protective effect (OR=0.41, 95% CI 0.26-0.65). Except for hypertension (OR=1.55, 95% CI 1.03-2.35), none of the analyzed components of metabolic syndrome were associated to BC risk. Particular increases of risk for premenopausal BC were found for family history in first degree relatives in certain subsets derived from the menstrual-reproductive history. Preventive strategies could broaden their scope if new studies confirm the present results, in view of the limited prevention measures that premenopausal BC currently has.     

Effect of obesity and other lifestyle factors on mortality in women with breast cancer

A few lifestyle characteristics before cancer diagnosis have been suggested to modify the prognosis of breast cancer. Follow-up information from 1,453 women with incident invasive breast cancer, diagnosed between 1991 and 1994 and interviewed within the framework of an Italian multicenter case-control study, was used to assess the effect of obesity and of a large spectrum of other factors on breast cancer mortality. Five hundred and three deaths, including 398 breast cancer deaths, were identified. Hazard ratios (HR) for all-cause and breast cancer mortality and corresponding 95% confidence intervals (CI), were calculated using Cox proportional hazards models and adjusted for age and breast cancer characteristics (stage and receptor status). Increased risk of death for breast cancer emerged for body mass index (BMI) >/= 30 kg/m(2) (HR = 1.38; 95% CI: 1.02-1.86), compared to <25, or waist-to-hip ratio (WHR) >/= 0.85 (HR = 1.27; 95% CI: 0.98-1.64), compared to <0.80, and the strongest association was observed for women with BMI >/=30 and high WHR (>/=0.85), compared to women with BMI <25 and WHR < 0.85 (HR = 1.57, 95% CI: 1.08-2.27). The unfavorable effect of high BMI was similar in women <55 and >/=55 years of age, whereas it was stronger in women with I-II stage than III-IV stage breast cancer. Low vegetable and fruit consumption and current or past smoking were also associated to marginally worse breast cancer survival. No significant relationship with survival after breast cancer emerged for several other major lifestyle factors, including physical activity, alcohol drinking, exogenous hormones use and fat intake. High BMI was the lifestyle risk factor that most consistently modified breast cancer prognosis in our study.     

Grand multiparity and incidence of endometrial cancer: a population-based study in Finland

The hormonal background of endometrial cancer is insufficiently characterised. We investigated the significance of parity, age at first birth, intensity between births, length of time from the first to the last birth and length of delivery-free premenopausal period in a cohort of grand multiparous (GM) women, i.e., women with at least 5 births. Data of the Population Register of Finland (86,978 GM-women) and the population-based Finnish Cancer Registry were combined. Standardised incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases by the expected number based on the national incidence rates. Multivariate relative risks (RRs) were estimated by Poisson regression analysis. The SIR for endometrial cancer among GM-women was low [419 cases; SIR=0.57, 95% confidence interval (CI) 0.52-0.63]. The RR of endometrial cancer was 0.58 (95% CI 0.34-0.97) among women giving their first birth at an age of more than 30 years compared to women with first birth before the age of 20. In ages 50+ (94% of endometrial cancer cases), the RR for women with at least 8 births was 0.63 (95% CI 0.44-0.92) compared to those with 5 births, and those with a birth period of 20+ years had RR=0.57 (95% CI 0.34-0.96) compared to those with a period of <10 years, while prolonged average intensity between births showed only a small protective effect. The RR of endometrial cancer also correlated with the length of premenopausal delivery-free period (RR = 0.61, 95% CI 0.44-0.86) for women with a short (<10 years) period compared to women with a long (>15 years) period. Our findings, that a large number of births, old age at first birth, a long birth period and a short premenopausal delivery-free period reduced the risk of postmenopausal endometrial cancer of GM-women, emphasise the protective role of progesterone and the stimulatory role of estradiol in the hormonal background of this disease.     

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.     

Risk factors for breast cancer among women in Bhopal urban agglomerate: a case-control study

Background: Breast cancer is the most common cancer in females worldwide, and the second leading cause of cancer deaths in women. The incidence is on the rise in India, and breast cancer is the second most common malignancy in Indian women. Objective: To assess the risk factors for breast cancer patients living in Bhopal. Study Design and Method: This case-control study was conducted in Bhopal urban agglomerate for a period of a year from October 2008 to August 2009. Demographic data and reproductive risk factor related information was collected using a structured questionnaire with analyses by Epi-info and SPSS 16. Results: A history of oral contraceptive pill use (OR=2.77, 95% CI: 1.15-6.65), history of not having breastfeeding (OR=3.49, 95% CI:1.22-9.97), over weight (OR=0.11, 95%CI:0.02-0.49), obese women ( OR=0.24, 95%CI: 0.06-0.88) and family history of breast cancer (OR=3.89, 95% CI: 1.01-14.92) were associated significantly with the occurrence of breast cancer on multivariate analysis. Conclusions: The findings of the present study suggests that positive family history of breast cancer and history of using OCP may be the epigenetic factors promoting the occurrence of breast cancer while breastfeeding reduces the possibility of acquiring breast cancer.     

Endocrine correlates of male breast cancer risk: a case-control study in Athens, Greece

We studied the relation of certain endocrine-related variables among 23 cases of male breast cancer and 76 apparently healthy male controls. There were significant inverse associations with smoking (P = 0.03), birth order (P = 0.02) and reported frequency of orgasms in later life (P = 0.0004). The study provides strong indirect evidence that endocrine factors are important in the aetiology of male breast cancer.     

Risk factors for breast cancer by age and menopausal status: a case-control study in Singapore

A case-control study was conducted among Singapore Chinese women, comprised of 200 histologically confirmed cases of breast cancer and 420 hospital controls. Subjects were interviewed on family history of breast cancer, social and demographic characteristics, reproductive history, and diet one year prior to interview. Differences in risk factors were observed according to menopausal status. In the premenopausal group, the most consistently significant nondietary effect was an increased risk with late age at first birth. In postmenopausal women, the most consistent nondietary effects were increased risks with nulliparity, tall stature, high educational status, and a family history of breast cancer. In premenopausal women, the strongest dietary effects were low risks with high intakes of polyunsaturated fatty acids (PUFA), -carotene, soya protein as a proportion of all protein, and a high risk with high red-meat intake. No dietary effects were observed in postmenopausal women. Examination of effects by 10-year age groups suggested that the differences in the effects of age at first birth, nulliparity, height, education, -carotene intake, and PUFA intake between premenopausal and postmenopausal women were at least partly attributable to age-related differences in the baseline distributions of these variables. The variation in the effects of red meat and soya protein appeared to be attributable mainly to menopausal status itself, which is consistent with the hypothesis that these factors operate on risk by way of hormonal mechanisms.Drs HP Lee and J Lee are with the Department of Community, Occupational and Family Medicine, National University of Singapore. Ms Gourley is with Gleneagles Hospital, Singapore. Dr Estève is with the International Agency for Research on Cancer, Lyon, France. Mr Duffy and Dr Day are with the Medical Research Council Biostatistics Unit, Cambridge, UK. Address correspondence to Dr HP Lee, Professor and Head, Department of COFM, National University of Singapore, Lower Kent Ridge Road, Singapore 0511. Funding for this study was provided by the International Agency for Research on Cancer.     

Epidemiologic and molecular risk factors for contralateral breast cancer among young women

Women diagnosed with a first breast cancer before the age of 45 years have a greater than 5.0-fold risk of developing a second primary contralateral breast cancer (CBC) than women in the general population have of developing a first breast cancer. Identifying epidemiologic or molecular factors that influence CBC risk could aid in the development of new strategies for the management of these patients. A total of 1285 participants in two case-control studies conducted in Seattle, Washington, who were 21-44 years of age when diagnosed with a first invasive breast carcinoma from 1983 to 1992, were followed through December 2001. Of them, 77 were diagnosed with CBC and 907 tumour tissues from first cancers were analysed. Women with body mass indices (BMIs) >/=30 kg m(-2) had a 2.6-fold greater risk (95% CI: 1.1-5.9) of CBC compared to women with BMIs 相似文献   

Comparison of age at first full-term pregnancy between women with breast cancer and women with benign breast diseases

Benign breast diseases have a broadly similar risk profile to that of breast cancer, possibly reflecting a similar underlying endocrine milieu. We have hypothesized that a crucial distinction between breast cancer and benign breast diseases is that mammary gland terminal differentiation has not been successfully accomplished among women who tend to develop breast cancer. From October 2001 to December 2002, information concerning breast cancer risk factors and sociodemographic characteristics was collected from 174 women with breast cancer and 116 women with benign breast diseases, all 30 years old or older, who were histologically diagnosed at a major prevention center in Athens, Greece. Among the examined breast cancer risk factors, only age at first full-term pregnancy was significantly associated with the odds of having breast cancer rather than benign breast disease, and the association was evident among premenopausal [odds ratio (OR) per 5 years = 1.76, 95% confidence interval (CI) 1.10-2.93] and postmenopausal (OR = 2.10, 95% CI 1.16-3.71) women, as well as among all women (OR = 1.93, 95% CI 1.34-2.70). There was no evidence that any of the remaining breast cancer risk factors could discriminate between breast cancer and benign breast diseases. We conclude that early age at first pregnancy may convey substantial protection against breast cancer risk among women with benign breast diseases, probably operating through induction of terminal differentiation of mammary gland cells. The finding is accentuated by the fact that women with benign breast diseases are already at a relatively high risk for breast cancer.     

Population-based case-control study of soyfood intake and breast cancer risk in Shanghai

We evaluated the association of soyfood intake and breast cancer risk in a population-based case-control study among Chinese women in Shanghai. Included in the study were 1459 cases and 1556 age-matched controls, with respective response rates of 91.1% and 90.3%. Usual soyfood intake was assessed using a food frequency questionnaire (FFQ). Separate analyses were performed for all subjects and for the subset who reported no recent change in soyfood intake. The intake levels of soyfoods among women in Shanghai are high, with 96.6% women reporting soyfood consumption at least once a week. A statistically non-significant reduced risk (odds ratio (OR) = 0.78 95% CI = 0.52-1.16) of breast cancer was observed among those who reported eating soyfood at least once a week. Compared to those in the lowest decile intake group, women in the highest decile intake group had a 30% reduced risk of breast cancer (OR = 0.66, 95% CI = 0.46-0.95), but no monotonic dose-response relation was observed (P for trend, 0.28). Stratified analyses showed that the inverse association was restricted primarily among women who had a high body mass index (BMI), with an adjusted OR of 0.30 (95% CI = 0.10-0.94) observed for the highest intake group. The reduction in risk was stronger for breast cancer positive for both oestrogen receptor (ER) and progesterone receptor (PR) (OR = 0.44, 95% CI = 0.25-0.78) than those with other ER/PR status. More pronounced inverse associations were observed in analyses among those who reported no recent change in soyfood intake than those conducted in all subjects. A dose-response relation between soyfood intake and breast cancer risk was observed in this subset of women (P for trend, 0.02), with an OR of 0.46 (95%CI = 0.28-0.75) for those in the highest decile intake group. No clear monotonic dose-response relation was found between soyfood intake and breast cancer risk among regular soy eaters, but nevertheless the results suggest that regular soyfood consumption may reduce the risk of breast cancer, particularly for those positive for ER and PR; the effect may be modified by body mass index.     

Breast cancer in Swedish women before age 50: evidence of a dual effect of completed pregnancy

We set out to detect a transient increase in risk of breast cancer following childbirth, the existence of which has been postulated, but for which empirical evidence is contradictory. Breast cancers and births occurring among the cohort of Swedish women born after 1939 were linked, yielding 3,439 cases and 25,140 age-matched controls with at least two children. Within three years of their last childbirth, women had an estimated rate of breast cancer of 1.21 (95 percent confidence interval [CI]=1.02–1.44) times that of women whose last birth was 10 or more years earlier, after adjustment for parity and age at first birth. Further analyses suggested that this effect reflected, in part, a small transient increase in breast cancer risk that lasts for about three years following completed pregnancy. The effect of age at first birth on breast cancer risk appears to be confounded by time since last birth; the parity-adjusted rate ratio for having a first birth at age 35 years or more compared with under 20 years is reduced from 1.72 (CI=1.14–2.58) to 1.36 (CI=0.88–2.09) on additional adjustment for time since last birth. A transient increase in breast cancer risk after childbirth thus appears to account for part of the effect of age at first birth on breast cancer risk.Ms Broeders contributed to the analyses during a three-month placement at LSHTM under the ERASMUS scheme.