Intrauterine environments and breast cancer risk: meta-analysis and systematic review

Introduction

Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses.

Methods

We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results.

Results

We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for ≥4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for ≥3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk.

Conclusion

Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.     

Obstetric history and mammographic density: a population-based cross-sectional study in Spain (DDM-Spain)

High mammographic density (MD) is used as a phenotype risk marker for developing breast cancer. During pregnancy and lactation the breast attains full development, with a cellular-proliferation followed by a lobular-differentiation stage. This study investigates the influence of obstetric factors on MD among pre- and post-menopausal women. We enrolled 3,574 women aged 45-68 years who were participating in breast cancer screening programmes in seven screening centers. To measure MD, blind anonymous readings were taken by an experienced radiologist, using craniocaudal mammography and Boyd's semiquantitative scale. Demographic and reproductive data were directly surveyed by purpose-trained staff at the date of screening. The association between MD and obstetric variables was quantified by ordinal logistic regression, with screening centre introduced as a random effect term. We adjusted for age, number of children and body mass index, and stratified by menopausal status. Parity was inversely associated with density, the probability of having high MD decreased by 16% for each new birth (P value < 0.001). Among parous women, a positive association was detected with duration of lactation [>9 months: odds ratio (OR) = 1.33; 95% confidence interval (CI) = 1.02-1.72] and weight of first child (>3,500 g: OR = 1.32; 95% CI = 1.12-1.54). Age at first birth showed a different effect in pre- and post-menopausal women (P value for interaction = 0.030). No association was found among pre-menopausal women. However, in post-menopausal women the probability of having high MD increased in women who had their first child after the age of 30 (OR = 1.53; 95% CI = 1.17-2.00). A higher risk associated with birth of twins was also mainly observed in post-menopausal women (OR = 2.02; 95% CI = 1.18-3.46). Our study shows a greater prevalence of high MD in mothers of advanced age at first birth, those who had twins, those who have breastfed for longer periods, and mothers whose first child had an elevated birth weight. These results suggest the influence of hormones and growth factors over the proliferative activity of the mammary gland.     

Risk factors for breast cancer at young ages in twins: an international population-based study

BACKGROUND: Breast cancer etiology in women may relate to exposures early in life as well as in adulthood, but it has been difficult to gain information on childhood variables, and evidence on their effects is very limited. Comparison of risk factor levels between affected probands and unaffected twins in twin pairs can provide a unique method to investigate risk factors that act in early life. METHODS: We conducted four population-based case-control studies of breast cancer risk in twins in Denmark, England and Wales, Finland, and Sweden and pooled the data from these studies. The case patients were 400 women with incident breast cancer before the age of 50 years, and the control subjects were their twin sisters who had not had breast cancer by that time. Data on risk factors (e.g., demographic and anthropomorphic variables, reproductive history, and family history) were collected by interview and by a mailed questionnaire and were analyzed by calculating matched odds ratios [ORs]. All statistical tests were two-sided. RESULTS: The risk of breast cancer was increased for women who were less obese (OR = 1.44, 95% confidence interval [CI] = 1.08 to 1.91) or taller (OR = 1.27, 95% CI = 0.95 to 1.70) than their co-twin at age 10 years, for women who developed breasts earlier than their co-twin (OR = 1.53, 95% CI = 1.14 to 2.06), and for women who had a smaller waist-to-hip ratio at age 20 years than their co-twin (OR = 1.79, 95% CI = 1.00 to 3.21). Analysis according to family history of breast cancer showed that the associations of childhood height and weight with risk of breast cancer were only apparent in women without a family history of breast cancer. CONCLUSIONS: Childhood growth before puberty may affect the risk of premenopausal breast cancer, at least in women without a family history of breast cancer. The distribution of body fat in young adulthood may also be related to breast cancer risk.     

Twinship and risk of postmenopausal breast cancer

BACKGROUND: Intrauterine exposure to high levels of endogenous estrogens has been hypothesized to increase the risk of breast cancer. Because estrogens and other pregnancy hormones are substantially elevated in twin pregnancies, and possibly more so in dizygotic twin pregnancies, we evaluated the association between aspects of twin membership (i.e., belonging to a twin pair) and the risk of breast cancer. METHODS: In a cohort of 29 197 postmenopausal Iowa women with no prior diagnosis of cancer (except for nonmelanoma skin cancer), breast cancer risk factors were determined by use of a mailed questionnaire in 1986 (baseline); twin membership, sex of the twin, and zygosity were determined by use of a follow-up questionnaire in 1992. RESULTS: Within the cohort, 1.8% (n = 538) of the women reported being a twin; of these, 24% (n = 130) were monozygotic twins, 63% (n = 337) were dizygotic twins, and 13% (n = 71) did not know their zygosity. From 1986 through 1996, 1230 breast cancers in the cohort were ascertained by linkage to the Iowa Cancer Registry. Compared with singletons, women who belonged to a twin pair were at elevated risk of breast cancer (multivariate-adjusted risk ratio [RR] = 1.72; 95% confidence interval [CI] = 1.22-2.42), with adjustment for educational level, family history of breast cancer, height, body mass index, body fat distribution, age at menarche, age at first live birth, use of hormone replacement therapy, and alcohol use. Multivariate-adjusted risk was elevated (in comparison with singletons) if the sex of the other twin was female (RR = 1.82; 95% CI = 1.20-2.75); however, this risk was limited to female dizygotic twins (RR = 2.14; 95% CI = 1. 21-3.79), since no excess risk was evident for monozygotic twins (RR = 1.04; 95% CI = 0.43-2.50). The risk to women with a male twin was also elevated (RR = 1.49; 95% CI = 0.80-2.78) in comparison with singletons, but this estimate was not statistically significant. CONCLUSIONS: This cohort study lends further support to the theory that there are important intrauterine influences on carcinogenesis of the breast.     

Intrauterine environment and breast cancer risk in a population-based case-control study in Poland

High estrogen exposure in utero may increase breast cancer risk later in life. However, studies of the associations between perinatal factors presumed to affect the fetal hormonal environment and breast cancer risk are inconsistent. We used data from a population-based case-control study of 2,386 incident breast cancers and 2,502 controls in Poland to evaluate risks associated with various perinatal characteristics. After adjusting for confounders, we found a significant trend (p = 0.01) of breast cancer risk with birth weight (OR = 1.54, 95% CI 1.08-2.19 for birth weights >4,000 g vs. <2,500 g). Subjects with a high birth order (> or =6) were at reduced risk (OR = 0.81, 0.61-1.06) when compared with first born subjects. Birth weight was somewhat a stronger risk predictor among subjects whose cancers were diagnosed at 50 years of age or older (OR = 1.84, 1.19-2.85) than among those with cancers diagnosed at younger ages (OR = 1.14, 0.61-2.12). Subjects whose mothers smoked during their pregnancies were at slightly higher risk than those who never smoked (OR = 1.21, 0.99-1.47), but the risk was similar to mothers who only smoked at other times (OR = 1.22, 0.81-1.84). Breast cancer risk was not related to paternal smoking, maternal age, gestational age or twin status. Our results add support to the growing evidence that some perinatal exposures may relate to breast cancer risk. Additional studies are needed to confirm associations and clarify the biologic mechanisms underlying these associations.     

Co-twin control and cohort analyses of body mass index and height in relation to breast, prostate, ovarian, corpus uteri, colon and rectal cancer among Swedish and Finnish twins

Associations between anthropometric measures and cancer have been studied previously, but relatively few studies have had the opportunity to control for genetic and early shared environmental factors. In this study, we analyzed 2 twin cohorts from Sweden born 1886-1925 (n = 21,870) and 1926-1958 (n = 30,279) and 1 from Finland born 1880-1958 (n = 25,882) including in total 78,031 twins, and studied the association between BMI and height and risk of prostate, breast, ovarian, corpus uteri, colon and rectal cancer. The cohorts were both analyzed through a co-twin control method and as traditional cohorts. In co-twin control analyses, older obese (BMI > or = 30 kg/m(2)) subjects (median age 56 years at baseline) were at higher risk of cancer of the corpus uteri (OR = 3.0; 95% CI 0.9-10.6), colon (OR = 1.9; 95% CI 0.8-4.5) and breast (OR = 2.5; 95% CI 1.3-4.2). For younger obese women (median age 30 years at baseline), an inverse tendency was observed for breast cancer (OR = 0.6; 95% CI 0.3-1.5, p for trend = 0.05). The tallest women had an increased risk of breast (OR = 1.8; 95% CI 1.3-2.7) and ovarian cancer (OR = 1.7; 95% CI 0.8-3.5). No consistent associations were found for prostate cancer either for BMI or height. There are some suggestions in our study that uncontrolled genetic or early shared environmental factors may affect risk estimates in studies of anthropometric measures and cancer risk, but do not explain observations of increased cancer risks related to BMI or height.     

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.     

Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population‐based case–control study

Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population‐based case–control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967–2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78–0.97), gestational hypertension (OR 0.90; 95% CI 0.86–0.93) and preeclampsia (OR 0.91; 95% CI 0.88–0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98–1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.     

Breast cancer risk in mothers of twins.

The risk of breast cancer associated with delivering a twin birth was examined in a population-based nested case-control study of nearly 4800 Swedish women with breast cancer and 47000 age-matched control subjects. All were aged less than 50 years and parous. After adjustment for age at first birth and parity, a 29% reduction in breast cancer risk was observed in mothers of twins relative to those who were not (odds ratio = 0.71, 95% confidence interval 0.55-0.91). These results provide evidence that women who bear twins are at reduced risk of breast cancer, one explanation for which may be their unusual levels of hormonal exposure.     

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.     

Risk factors for hormone receptor-defined breast cancer in postmenopausal women.

The effect of classic breast cancer risk factors on hormone receptor-defined breast cancer is not fully clarified. We explored these associations in a Swedish population-based study. Postmenopausal women ages 50 to 74 years, diagnosed with invasive breast cancer during 1993 to 1995, were compared with 3,065 age frequency-matched controls. We identified 332 estrogen receptor (ER-) and progesterone receptor (PR-) negative, 286 ER+PR-, 71 ER-PR+, 1,165 ER+PR+, and 789 tumors with unknown receptor status. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Women ages >or=30 years, compared with those ages 20 to 24 years at first birth, were at an increased risk of ER+PR+ tumors (OR, 1.5; 95% CI, 1.2-1.8) but not ER-PR- tumors (OR, 1.1; 95% CI, 0.8-1.6). Women who gained >or=30 kg in weight during adulthood had an approximately 3-fold increased relative risk of ER+PR+ tumors (OR, 2.7; 95% CI, 1.9-3.8), but no risk increase of ER-PR- tumors (OR, 1.0; 95% CI, 0.5-2.1), compared with women who gained <10 kg. Compared with never users, women who used menopausal estrogen-progestin therapy for at least 5 years were at increased risk of ER+PR+ tumors (OR, 3.0; 95% CI, 2.1-4.1) but not ER-PR- tumors (OR, 1.3; 95% CI, 0.7-2.5). In conclusion, other risk factors were similarly related to breast cancer regardless of receptor status, but high age at first birth, substantial weight gain in adult age, and use of menopausal estrogen-progestin therapy were more strongly related to receptor-positive breast cancer than receptor-negative breast cancer.     

First pregnancy characteristics and subsequent breast cancer risk among young women

There is growing evidence that perinatal factors associated with altered gestational hormones may influence subsequent breast cancer risk in the mother. Events occurring during the first pregnancy may be particularly important. In this matched case-control study, we investigated the relation between characteristics of a woman's first pregnancy and her later breast cancer risk using linked records from the New York State birth and tumor registries. Cases were 2,522 women aged 22 to 55 diagnosed with breast cancer between 1978 and 1995 and who had also completed a first pregnancy in New York State (NY) at least 1 year prior to diagnosis. Controls were 10,052 primiparous women not diagnosed with breast or endometrial cancer in NY and matched to cases on county of residence and date of delivery. Information on factors characterizing the woman's first pregnancy was obtained from the pregnancy record of each subject. The association of these factors to breast cancer risk was assessed using conditional logistic regression. Extreme prematurity (< 32 weeks gestational age) was associated with elevated maternal breast cancer risk [adjusted odds ratio (OR)=2.1, 95% confidence interval (CI) 1.2,3.9], as were abruptio placentae (OR = 1.8, CI 1.1,3.0) and multifetal gestation (OR=1.8, CI 1.1,3.0). Preeclampsia was associated with a marked reduction in breast cancer risk among women who bore their first child after age 30 (OR=0.3, CI 0.2,0.7) and in the first 3 years after delivery (OR=0.2 (0.1-0.9). These findings suggest that certain perinatal factors influence maternal breast cancer risk and offer indirect support for a role of gestational hormones, and particularly gestational estrogens, in the etiology of breast cancer.     

Twinning and the Incidence of Breast and Gynecological Cancers (United States)

Increasing epidemiological and experimental evidence indicates that the carcinogenic pathway in the breast and female reproductive organs is driven, at least in part, by factors associated with reproduction. We conducted a retrospective cohort study, comparing the risk of ovarian, breast, endometrial, and cervical cancers among women who had records of at least one twin pregnancy, compared with women who had given birth to only single children. Subjects were selected from the Utah Population Database, which consists of multiple linked datasets including genealogy, births and deaths and cancer registries. We used Poisson regression to calculate relative risks, adjusted for the number of pregnancies and the age of the mother at the birth of first and last children, with singleton mothers as the reference group in each case. The risks of breast and ovarian cancers did not differ between mothers of twins and mothers of single children. The risk of endometrial cancer was slightly lower in mothers of twins than in mothers of singleton children (RR = 0.90, 95% CI 0.67-1.21). Conversely the risk of cervical cancer was higher among twin mothers (RR = 1.78, 95% CI 0.88-3.52). This latter finding supports previous data suggesting that reproductive hormones act as cofactors in the etiology of cervical cancer.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women: a case-control study

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR = 0.45, 95% CI = 0.30-0.66; OR = 0.34, 95% CI = 0.22-0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR = 0.36, 95% CI = 0.14-0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR=0.45, 95% CI=0.30–0.66; OR=0.34, 95% CI=0.22–0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR=0.36, 95% CI=0.14–0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Effects of Menstrual and Reproductive Factors on the Risk of Breast Cancer: Meta-analysis of the Case-Control Studies in Japan

To elucidate the magnitude of the effect of menstrual and reproductive factors on breast cancer occurrence among Japanese women, we reviewed eight case-control studies previously conducted in Japan and used a quantitative method (meta-analysis) to summarize the data. While individual studies have different methods and populations, the estimated odds ratios (ORs) in the studies were statistically homogeneous for all study variables. It was confirmed that early age at menarche, late age at first birth, and premenopausal status are significantly associated with risk of breast cancer; an estimated combined OR of 0.68 (95% confidence interval (CI): 0.59-0.77) was obtained for women with onset of menstruation after age 16 compared to those before age 14. Nulliparous women had higher risk than women with first birth before age 25 (OR=1.56 95%, CI: 1.27-1.91). The OR for women with first birth after age 35 was 2.26 (95% CI: 1.85-2.77) compared to women at first birth before age 25. Premenopausal women had a higher risk than women with menopause before age 50 (OR=2.21, 95% CI: 1.53-3.20). We also found a significant protective effect of high parity after controlling for age at first birth and the other menstrual factors. The OR estimate for 3 or more births compared to nulliparity was 0.68 (95% CI: 0.54-0.86). The meta-analysis provided quantitative estimates of breast cancer risk among Japanese women with improved precision.     

Gestational age and fetal growth in relation to maternal ovarian cancer risk in a Swedish cohort.

BACKGROUND: Pregnancy influences subsequent maternal ovarian cancer risk. To date, there is limited evidence whether two characteristics of pregnancy, gestational age and birth weight, could modify risk. MATERIALS AND METHODS: We studied 1.1 million Swedish women who delivered singleton births between 1973 and 2001. Information on infant gestational age and birth weight was abstracted from the nationwide Swedish Birth Register. Women were followed prospectively through linkage with other population-based registers for occurrence of ovarian cancer, death, or emigration through 2001. Hazard ratios [relative risk (RR), 95% confidence interval (95% CI)] from Cox models were used to estimate associations between gestational age, birth weight, and epithelial ovarian cancer risk. RESULTS: During 12.6 million person-years, 1,017 epithelial ovarian cancers occurred. Mean age at diagnosis was 43 years. Compared with women with term deliveries (>/=40 weeks), women with moderately (35-36 weeks) or very (<35 weeks) preterm deliveries had increased risks of epithelial ovarian cancer (RR 1.4, 95% CI 1.0-2.0 and RR 2.3, 95% CI 1.3-3.8, respectively). In contrast, women giving birth to small-for-gestational-age babies had a reduced risk (RR 0.7, 95% CI 0.4-1.0). Stratifying on birth weight and gestational age, there was a strong protective effect of low birth weight on maternal risk of epithelial ovarian cancer among term deliveries, whereas birth weight seemed to have little effect among preterm births (P(interaction) = 0.022). CONCLUSIONS: Our results lend further support that the hormonal milieu of a pregnancy may modify long-term risk of developing ovarian cancer. 32).     

Risk Factors for Breast Cancer in Iranian Women Aged Less than 40 Years

This case-control study was carried out in a university-affiliated teaching hospital, Tehran city, Iran. A total of312 newly diagnosed cases aged less than 40 years old participated and were matched for age and ethnicity with312 controls. The results showed that in women who never married (OR=2.42 95%CI=1.51-3.88) (P<0.001), hada family history of breast cancer (OR=7.07 95%CI=2.95-16.99) (P<0.001), a low age of menarche (OR=0.1 95%CI=0.04-0.23) (P<0.001)), lower parity (OR=13.3 95% CI=3.89-45.66) (P<0.001) and took oral contraceptive pills(OR= 2.83 95% CI=1.87-4.24) (P<0.000) were at increased risk. A direct association with age at first birth wasalso evident(P=0.041), with a significantly inverse association between duration of lactation and breast cancer risk(p=0.016). On multivariate logistic regression, parity, family history of breast cancer, use of oral contraceptivepills, and age at first birth remained significant. In women lower than 40 years of age, breast cancer risk wassignificantly higher in women with parity ≥4 compared with nulliparity but no association emerged with historyof breast-feeding. Other risk factors were similar to those described in breast cancer epidemiology at any age.     

Birth weight as a predictor of breast cancer: a case-control study in Norway

The hypothesis that birth weight is positively associated with adult risk of breast cancer implies that factors related to intrauterine growth may be important for the development of this malignancy. Using stored birth records from the two main hospitals in Trondheim and Bergen, Norway, we collected information on birth weight, birth length and placenta weight among 373 women who developed breast cancer. From the same archives, we selected as controls 1150 women of identical age as the cases without a history of breast cancer. Information on age at first birth and parity were collected from the Central Person Registry in Norway. Based on conditional logistic regression analysis, breast cancer risk was positively associated with birth weight and with birth length (P for trend=0.02). Birth weights in the highest quartile (3730 g or more) were associated with 40% higher risk (odds ratio, 1.4, 95% confidence interval, 1.1-1.9) of breast cancer compared to birth weights in the lowest quartile (less than 3090 g). For birth length, the odds ratio for women who were 51.5 cm or more (highest quartile) was 1.3 (95% confidence interval, 1.0-1.8) compared to being less than 50 cm (lowest quartile) at birth. Adjustment for age at first birth and parity did not change these estimates. Placenta weight was not associated with breast cancer risk. This study provides strong evidence that intrauterine factors may influence future risk of breast cancer. A common feature of such factors would be their ability to stimulate foetal growth and, simultaneously, to influence intrauterine development of the mammary gland.     

Birth characteristics and adult cancer incidence: Swedish cohort of over 11,000 men and women

Associations between larger size at birth and increased rates of adult cancer have been proposed but few empirical studies have examined this hypothesis. We investigated overall and site-specific cancer incidence in relation to birth characteristics in a Swedish population-based cohort of 11,166 singletons born in 1915-1929 for whom we have detailed obstetric data and who were alive in 1960. A total of 2,685 first primary cancers were registered during follow-up from 1960 to 2001. A standard deviation (SD) increase in birth weight for gestational age (GA) was associated with (sex-adjusted) increases of 13% (95% CI = 0.03-0.23) in the rates of digestive cancers and of 17% (95% CI = 0.01-0.35) in the rates of lymphatic cancers. Women who had higher birth weights also had increased rates of breast cancer under age 50 years (by 39% per SD increase; 95% CI = 0.09-0.79), but reduced rates (by 24%; 95% CI = 0.07-0.38) of endometrial (corpus uteri) cancer at all ages. There was no evidence of associations with other cancer sites. For overall cancer incidence, men had an 8% increased risk at all ages per SD increase in birth weight for GA while women only had an increased risk under age 50 years (mainly driven by the association with breast cancer). These findings provide evidence of a modest association of birth size and adult cancer risk, resulting from positive associations with a few cancer sites and a possible inverse association with endometrial cancer.