Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study

The incidence of breast cancer among Japanese women, a traditionally low-risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38,159 Japanese women, aged 40-79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow-up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P=0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P=0.05), the association being very apparent among menopausal women (trend P=0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72-6.21) and 3.33 (1.07-10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women.     

Role and impact of menstrual and reproductive factors on breast cancer risk in Japan.

The aim of this study was to clarify the role and impact of menstrual and reproductive factors in relation to breast cancer and its hormone receptor-defined subtype, overall and separately among premenopausal and postmenopausal women in a low-risk population, using data from the Japan Public Health Center-based Prospective study. A total of 55 537 women aged 40-69 years completed a self-administered questionnaire, which included items about menstrual and reproductive history. During 1990-2002, 441 newly diagnosed cases of breast cancer were identified. Early age at menarche for premenopausal women, late age at natural menopause, nulliparity and low parity for both premenopausal and postmenopausal women, and late age at first birth for postmenopausal women were significantly associated with an increased risk of breast cancer. No overall significant associations were seen between the use of exogenous female hormones or breast feeding and breast cancer risk. Age at menarche and age at natural menopause were somewhat more closely associated with the risk of progesterone receptor-negative than positive breast cancer although no difference was observed for estrogen receptor status. Risks associated with parity, number of births and age at first birth did not significantly differ by hormone receptor-defined breast cancer. Our findings suggest that menstrual and reproductive factors may play an important role in the development of breast cancer among low-risk populations, similarly as they do in Western populations, and that risk factors might differ by hormone receptor status.     

A prospective study of reproductive and menstrual factors and colon cancer risk in Japanese women: findings from the JACC study

The effects of reproductive factors on the etiology of colon cancer in Asian populations remain unexplored. So we examined 38,420 Japanese women aged 40-79 years who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During an average 7.6 years of follow-up, we documented 207 incident colon cancers. Multivariate analysis indicated that colon cancer risk was likely to be lower among parous women than among nulliparous. Women who had two abortions or more had a 72% higher risk of developing colon cancer [relative risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared with women who never had an abortion. The RR of colon cancer among postmenopausal women significantly decreased with increasing age at menarche (trend P = 0.01). No apparent association between colon cancer and gravida, age at first birth, age at menopause, or duration of menstruation was seen. These prospective data support the hypothesis that female reproductive events modify colon cancer risk, and suggest that reproductive factors, particularly age at menarche and having an abortion, may be of importance in the etiology of colon cancer among Japanese women.     

Parity and other reproductive factors and risk of adenomatous polyps of the distal colorectum (United States)

Evidence for an effect of reproductive factors on colorectal carcinogenesis is inconsistent and little is known about their role in development of precursor adenomatous polyps. We evaluated the relation between reproductive factors and distal colorectal adenomas (n = 982) during14 years of follow up of 26,983 participants in the Nurses' Health Study(United States). The women were free of diagnosed cancer or polyps in 1980,underwent endoscopy 1980-94, and had reported on their parity, oral contraceptive (OC) use, and ages at menarche, first term-pregnancy, and menopause. We calculated relative risks (RR) and 95 percent confidence intervals (CI) using multiple logistic regression. Women with higher parity had an increased risk of adenomas of the distal colorectum (P trend = 0.004;6+ cf 0 parity: RR = 1.3, CI = 0.9-1.8) or distal colon (P trend = 0.002, RR= 1.7, CI = 1.2-2.6). This association was significantly stronger among women with a family history of colorectal cancer ( P interaction = 0.03); comparing6+ term-pregnancies with nulliparity, among those with a family history, the RR for distal colon adenoma was 3.2 (CI = 1.4-7.2), while among those without a family history, the RR was 1.3 (CI = 0.8-2.2). We observed no association for distal colorectal adenoma and age at menarche, age at first term-pregnancy, ever use of OCs, or menopausal status. Further work is needed to clarify the relation of parity with colon adenoma risk. This revised version was published online in July 2006 with corrections to the Cover Date.     

Bladder cancer and reproductive factors among women in Spain

Hormonal factors, possibly related to reproductive characteristics, may play a role in the risk of bladder cancer among women. To study this, we investigated the effects of reproductive factors on female bladder cancer risk. Information on reproductive and other risk factors was gathered in personal interviews from 152 female cases and 166 matched controls from 18 hospitals in five regions of Spain during 1998–2001. Logistic regression was used to estimate the association between bladder cancer and reproductive factors, including ever-parous status, age at first live birth, age at last live birth, age at menarche, age at menopause, menopausal status, and duration of menstruation. After adjustment for age, smoking, and high-risk occupation, ever-parous women were at decreased risk relative to nulliparous women (odds ratio = 0.43, 95% confidence interval = 0.21–0.87). There was no consistent pattern in risk with the age- or duration-related reproductive factors (e.g., age at first live birth, age at last live birth, age at menarche, age at menopause, menopausal status, and duration of menstruation) that we evaluated. Women have a lower risk of bladder cancer than men, and hormonal factors related to childbearing may play a role.     

Reproductive factors, exogenous hormone use and bladder cancer risk in a prospective study

Sex is a consistent predictor of bladder cancer: men experience 2-4-fold higher age-adjusted rates than women in the U.S. and Europe. The objective of this study was to examine whether hormone-related factors are associated with bladder cancer in women. We examined parity, age at menarche, age at first birth, age at menopause, oral contraceptive use and menopausal hormone therapy (HT) use and bladder cancer risk in the Breast Cancer Detection Demonstration Project Follow-Up Study. Endpoint and exposure information was collected on 54,308 women, using annual telephone interviews (1980-86) and 3 mailed, self-administered questionnaires (1987-98). During an average follow-up time of 15.3 years, 167 cases of bladder cancer were identified. Univariate and adjusted rate ratios (RRs) were estimated using Poisson regression. Parity, age at menarche, age at first birth, age at menopause, and oral contraceptive use were not associated with bladder cancer risk. The majority of menopausal women who took HT used estrogen therapy (ET). Postmenopausal women with less than 4 years, 4-9 years, 10-19 years and 20 or more years of ET use had RRs of 1.55 (95% CI = 0.96-2.51), 1.00 (95% CI = 0.49-2.04), 1.23 (95% CI = 0.62-2.43) and 0.57 (95% CI = 0.14-2.34), respectively, compared with nonusers (p = 0.50). Findings from this study are not consistent with the hypothesis that hormone-related factors in women are associated with bladder cancer.     

Reproductive factors,exogenous female hormone use and breast cancer risk in Japanese: the Miyagi Cohort Study

The incidence of breast cancer among Japanese women is substantially increasing. This population-based prospective cohort study in Japan evaluated the associations of reproductive factors and exogenous female hormone use with breast cancer risk, both overall and separately among premenopausal and postmenopausal women. A total of 24,064 women aged 40–64 were followed from 1990 to 2003. During 309,424 person-years of follow-up, 285 breast cancer cases were documented. In overall evaluation, nulliparity was significantly associated with an increased risk of breast cancer. There was a significant decrease in risk with increasing parity number among parous women (trend P = 0.008). No association was observed between age at menarche or age at first birth and breast cancer risk. Neither oral contraceptive (OC) use nor the use of exogenous female hormones other than OC was associated with breast cancer risk. The evaluation according to menopausal status revealed that nulliparity and parity number were significantly related to breast cancer risk only among postmenopausal women. Later age at natural menopause was associated with an increased risk of breast cancer among postmenopausal women (trend P = 0.02). Our findings suggest that parity number and age at menopause have great effects on breast cancer risk among Japanese women.     

Reproductive factors,exogenous hormone use and risk of lymphoid neoplasms among women in the National Institutes of Health‐AARP Diet and Health Study Cohort

Reasons for higher incidence of lymphoid neoplasms among men than women are unknown. Because female sex hormones have immunomodulatory effects, reproductive factors and exogenous hormone use may affect risk for lymphoid malignancies. Previous epidemiologic studies on this topic have yielded conflicting results. Within the National Institutes of Health‐AARP Diet and Health Study cohort, we prospectively analyzed detailed, questionnaire‐derived information on menstrual and reproductive factors and use of oral contraceptives and menopausal hormone therapy among 134,074 US women. Using multivariable proportional hazards regression models, we estimated relative risks (RRs) for 85 plasma cell neoplasms and 417 non‐Hodgkin lymphomas (NHLs) identified during follow‐up from 1996 to 2002. We observed no statistically significant associations between plasma cell neoplasms, NHL, or the 3 most common NHL subtypes and age at menarche, parity, age at first birth, oral contraceptive use or menopausal status at baseline. For menopausal hormone therapy use, overall associations between NHL and unopposed estrogen and estrogen plus progestin were null, with the potential exception of an inverse association (RR = 0.49, 95% CI, 0.25–0.96) between use of unopposed estrogen and diffuse large B‐cell lymphoma (DLBCL), the most common NHL subtype, among women with a hysterectomy. These data do not support an important role for reproductive factors or exogenous hormones in modulating lymphomagenesis. © 2008 Wiley‐Liss, Inc.     

Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition

Background:

It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear.

Methods:

We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use.

Results:

Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41–0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59–0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ⩽45 years: HR, 1.46; 95% CI, 1.06–1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk.

Conclusion:

This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.     

Reproductive, menstrual, and other hormone-related factors and risk of renal cell cancer

A role of hormone-related factors in renal cell cancer (RCC) etiology has been hypothesized, but the epidemiological evidence is inconsistent. The present study aimed at evaluating the effect of reproductive, menstrual and other gender-specific variables on RCC risk among women. This study is part of a larger hospital-based, case-control study on RCC risk, conducted in northern, central and southern Italy. Cases were 273 women, below age 80, with histologically confirmed, incident RCC. Controls were 546 women hospitalized for acute, nonneoplastic conditions, frequency-matched to cases by age and center. Odds ratios (OR) and 95% confidence intervals (CI) were computed using multiple logistic regression models. RCC risk was inversely related to age at first birth (OR = 0.7, 95% CI 0.5-1.0, for >/= 25 years vs. <25 years). Hysterectomy was found to double RCC risk (OR = 2.3, 95% CI 1.3-4.2). A negative association of borderline-statistical significance emerged for age at menarche, whereas, no associations were found between RCC risk and parity, menopausal status, age at menopause and use of hormone replacement therapy or oral contraceptives. Our findings give support to a role of hysterectomy in increasing RCC risk without corroborating, however, a major role of female hormone-related factors.     

Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women

The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45-0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12-2.38) and 1.35 (95% CI 1.02-1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60-1.04), 0.69 (95% CI 0.54-0.88), 0.66 (95% CI 0.51-0.85) and 0.64 (95% CI 0.48-0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer.     

Reproductive risk factors for incident bladder cancer: Iowa Women's Health Study

We studied the association between reproductive factors and bladder cancer incidence in a prospective cohort study of 37,459 Iowa women aged 55-69 years and initially free from cancer in 1986. Women reported reproductive history and were followed prospectively through 2003. After adjusting for age and smoking, there was an inverse association between age at menopause and incident bladder cancer (n = 192). Compared with menopause at age > or =48, the hazard ratio (HR) of bladder cancer was 1.32 (95% CI; 0.90-1.94) for menopause at 43-47, and 1.60 (95% CI; 1.06-2.39) for < or =42 (p-trend = 0.02). The associations were similar for ages at natural and surgical menopause. In addition, women with a history of bilateral oophorectomy had an increased risk of bladder cancer compared with those who did not undergo bilateral oophorectomy: HR = 1.58 (95% CI; 1.12, 2.22). Finally, there was an indication of a positive association between bladder cancer and shorter lifetime years of ovulation (p-trend = 0.09). There were no associations between incident bladder cancer and age at first birth, number of births, age at menarche, use of hormone replacement therapy or any other reproductive characteristics. This study provides evidence that increased risk of bladder cancer is associated with earlier age at menopause in postmenopausal women.     

Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis

Estrogens may influence gastric cancer risk, but published studies are inconclusive. We therefore carried out a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors and with use of estrogen- and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and review of citations yielded a total of 28 independent studies, including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95% CIs were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR = 0.74, 95% CI: 0.63-0.86) and HRT (RR = 0.77; 95% CI: 0.64-0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR = 1.82; 95% CI: 1.39-2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms.     

Breast cancer risk factors in Italian women: a multicentric case-control study

To evaluate the importance of several risk factors for breast cancer in the Italian female population, a large multicentric case-control study was conducted in 10 breast clinics in Italy. The study included 1,556 women affected by breast cancer, histologically and/or cytologically confirmed. Controls were 1,505 women admitted to a hospital in the same town, matched with cases for residence and with the same age distribution of the Italian female population. The risk factors considered in this study were family history of breast cancer, reproductive history, height and weight, use of oral contraceptives, other hormonal therapies and smoking history. The results of this study confirm the significant role of a positive family history of breast cancer (RR = 2.37); the relative risk was even higher when a first-degree relative was affected or the breast cancer was bilateral. The analysis of the reproductive history showed a significant trend of increasing risk with increasing age at first birth and, although less evident, with increasing number of children. Quetelet's index (kg/m-2) was positively correlated with breast cancer risk, mostly in postmenopausal women. Among other studied factors, only late age at menopause confirmed an increased risk for breast cancer, whereas age at menarche, use of oral contraceptives and smoking histories did not show any significant correlation with breast cancer risk. These results are in substantial agreement with other international studies, but represent an interesting contribution to studies about the Italian female population.     

Menstrual and reproductive factors in relation to risk of endometrial cancer in Chinese women

Menstrual, reproductive and contraceptive factors have been associated with risk of endometrial cancer in populations where the incidence of this tumor is high. To investigate associations between these factors in a low-risk population with a low prevalence of hormone replacement therapy, we conducted a cohort study among 267,400 women employed in the textile industry in Shanghai, China. Menstrual, reproductive and other factors were ascertained at baseline in 1989–1991, and women were followed for incident endometrial cancer through 31 December 1998 (n = 206). Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Risk of endometrial cancer decreased with increasing age at menarche (p-trend = 0.004). Among menopausal women, risk increased with age at menopause and increasing years of menstruation. Compared to women with one live birth, risk was increased in relation to nulliparity (Hazard ratio = 3.95, 95% CI 1.43–10.86). Risk was decreased with increasing age at first live birth (p-trend = 0.03). There was a decreased risk associated with ever use of an intrauterine device (HR = 0.56, 95% CI 0.35–0.88) and use of oral contraceptives for ≥2 years (HR = 0.50, 95% CI 0.23–1.07). This prospective study confirms findings from previous case–control studies relating menstrual, reproductive, and contraceptive factors and endometrial carcinoma.     

International renal-cell cancer study. V. Reproductive factors,gynecologic operations and exogenous hormones

The relationships between reproductive factors, exogenous hormones and renal-cell cancer were examined in an international, multicenter, population-based, case-control study undertaken in 1989-1991. Data from 5 centers situated in Australia, Denmark, Germany, Sweden and the United States included for analysis 608 women with renal-cell cancer and 766 female controls. A significant trend in risk (p = 0.002) was associated with number of births, with an 80% excess risk for 6 or more births [RR = 1.8, 95% confidence interval (CI) = 1.1 to 2.9] compared with one birth. A decreasing risk was seen for increasing age at first birth, although this was confounded by body-mass index and number of births. A suggestive reduction of risk was also seen for increasing age at menarche. Age at menopause was unrelated to risk of renal-cell cancer. An increased risk was observed for women having had both a hysterectomy and an oophorectomy. Use of oral contraceptives in non-smoking women reduced the risk of renal-cell cancer (RR = 0.5, 95% CI = 0.4 to 0.8); this reduction increased with longer duration of use. No association was observed for estrogen replacement therapy. Our results indicate that certain hormonal and reproductive variables may be related to risk of renal-cell cancer and deserve further investigation, both epidemiologically and experimentally. © 1995 Wiley-Liss, Inc.     

Reproductive factors and risk of premenopausal breast cancer by age at diagnosis: Are there differences before and after age 40?

We examined the relationship between reproductive factors and risk of premenopausal breast cancer among women less than age 40 compared with older premenopausal women. We documented 374 incident cases of breast cancer diagnosed before age 40, and 2,533 cases diagnosed at age 40 and older among premenopausal women in the Nurses’ Health Study cohorts. Biennial questionnaires were used to determine age at menarche, age at first birth, parity, breastfeeding, and other reproductive factors. Multivariate relative risks (RR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models within age at diagnosis groups. Tumors in younger women were significantly more likely to be higher grade, larger size, and hormone receptor negative than were tumors in older premenopausal women (p < 0.0001). There was no significant heterogeneity according to age in associations between reproductive factors and risk of premenopausal breast cancer. First birth at age 30 or older increased breast cancer risk in both age groups (age <40: RR 1.10, 95 % CI 0.80–1.50; age ≥40: RR 1.16, 95 % CI 1.02–1.32; p-heterogeneity = 0.44). Risk of premenopausal breast cancer decreased with each additional year of age at menarche in both age groups (age <40: RR 0.93, 95 % CI 0.87–0.99; p trend = 0.02; age ≥40: RR 0.94, 95 % CI 0.91–0.97; p trend = <0.0001). Among premenopausal parous women, breastfeeding was protective regardless of age at diagnosis (age <40: RR 0.84, 95 % CI 0.57–1.22; age ≥40: RR 0.85, 95 % CI 0.72–0.99; p-heterogeneity = 0.79). In the largest prospective examination of reproductive risk factors and risk of breast cancer before and after age 40, we found that younger women were more likely to develop tumors with less favorable prognostic characteristics. However, associations between reproductive factors and risk of breast cancer were similar regardless of age at diagnosis of premenopausal breast cancer.     

Menstrual and reproductive factors, exogenous hormone use, and risk of thyroid carcinoma in postmenopausal women

Purpose

To investigate the association of reproductive factors and hormone therapy, including type of hormone therapy, with risk of thyroid cancer in postmenopausal women.

Methods

We assessed these associations with risk of incident thyroid cancer in a cohort of 145,007 postmenopausal women enrolled in the Women’s Health Initiative. Over 12.7?years of follow-up, 296 cases of thyroid cancer were identified, including 243 with papillary thyroid cancer. Cox proportional hazards models were used to estimate hazard ratios and 95?% confidence intervals for exposures of interest.

Results

In both age-adjusted and multivariable-adjusted analyses, menstrual and reproductive factors including age at menarche, age at menopause, age at first birth, age at last live birth, parity, duration of breastfeeding, miscarriages, stillbirths, hysterectomy, bilateral oophorectomy, and use of oral contraceptives were not associated with risk of all thyroid cancer or papillary thyroid cancer. In addition, ever use of menopausal hormone therapy, current or former use, duration of use, and type were not associated with risk.

Conclusion

We found little support for associations of reproductive or hormonal factors with risk of developing thyroid cancer. Importantly, our study showed no association of type of hormone therapy used with thyroid cancer risk.     

Epidemiology of reproductive and hormonal factors in thyroid cancer: evidence from a case-control study in the Middle East.

Thyroid cancer is the second most common neoplasm among women in Kuwait and several other countries in the Middle East. Most of these countries also have relatively high birth and total fertility rates. To examine potential relationships between reproductive and hormonal factors and thyroid cancer, we conducted a population-based case-control interview study among 238 women diagnosed with thyroid cancer and a similar number of individually matched controls in Kuwait. Among the demographic variables, women with 12+ years of education had a significantly reduced risk of thyroid cancer (OR = 0.4; 95% CI: 0.2-0.8; p-trend <0.05). The average age at diagnosis (+/-SD) of thyroid cancer was 34.7 +/- 11 years. Events such as age at menarche, pregnancy, menopausal status and age at menopause were not associated with thyroid cancer. There was an association with age at last pregnancy and parity. Women who had their last pregnancy at ages > or = 30 years were at a significantly increased risk (OR = 2.1; 95% CI: 1.2-3.8); there was also a significant trend in risk with increasing age at last pregnancy. There was a modest increase in risk among women who had borne > or = 5 children (OR = 1.5; 95% CI: 0.9-2.5). A joint analysis of these factors showed that childbearing during the latter half of reproductive life had a substantial effect on the incidence of thyroid cancer; for any given level of parity, there was about a 2-fold increased risk if the age at last pregnancy was > or = 30 years. A substantial recent-birth effect, in relation to subsequent diagnosis of thyroid cancer, was observed during the second and third year after a birth (OR = 2.0; 95% CI: 1.0-4.1). In contrast, spontaneous abortion seemed to have a protective effect. There was a significant decrease in risk among women who had a miscarriage as outcome of first pregnancy (OR = 0.1; 95% CI: 0.03-0.4) and those who had experienced > or = 3 miscarriages (OR = 0.3; 95% CI: 0.1-0.8; p-trend <0.05). Overall, any female hormone use was not associated with thyroid cancer risk. New association is suggested for a history of post-partum thyroiditis (OR = 10.2; 95% CI: 2.3-44.8). These data support the hypothesis that reproductive factors and patterns may influence, or contribute to, the risk of thyroid cancer among women.     

Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study

The importance of age at menarche, age at menopause, height, and obesity as risk factors for breast cancer, and the possible interactions among these factors in breast cancer causation were investigated in a data set collected in the late 1960's, in an international multicenter case-control study. Multiple logistic regression procedures were used to model data from 3,993 breast cancer cases and 11,783 controls from 7 study centers representing the range of international variation of breast cancer incidence. Height and obesity (measured through the weight/height2 index) were independent risk factors for breast cancer among post-menopausal but not pre-menopausal women; post-menopausal women taller by 10 cm had a 12% higher risk of breast cancer (95% confidence interval, CI, 3-21%) and post-menopausal women of average height (say 158 cm) had an 11% higher risk of breast cancer (CI 7-16%) when they were heavier by 10 kg (and, therefore, more obese by 4 kg/m2). Age at menarche was a risk factor among both pre-menopausal and post-menopausal women, a delay of 2 years corresponding to a 10% reduction in breast cancer risk (CI 6-15%). Age at menopause was also a breast cancer risk factor, women with menopause at each 5 year age difference having a 17% higher risk of breast cancer (CI 11-22%). There is evidence of an interaction (deviation from the logistic regression-postulated multiplicativity) between obesity and age at menarche, implying that the protective effect of late menarche may not apply to overweight women or that late menarche may become detrimental in obese women. The estimated relative risk coefficients, when applied to average risk factor levels observed among control women, can explain only a small fraction of the difference in breast cancer incidence between Boston and Tokyo.