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.     

Benign thyroid disease and dietary factors in thyroid cancer: a case-control study in Kuwait

We conducted a population-based study of 313 case-control pairs in Kuwait to examine the aetiology of thyroid cancer, the second most common neoplasm among women in this and several other countries in the Gulf region. Among the demographic variables, individuals with 12+ years of education had a significantly reduced risk of thyroid cancer (OR=0.6; 95% CI: 0.3-0.9). The average age at diagnosis (+/-s.d.) of thyroid cancer was 34.7+/-11 years in women and 39+/-13.4 years in men. History of thyroid nodule was reported only by cases (n=34; 10.9%; lower 95% CI: 12.0); and goitre by 21 cases and four controls (OR=5.3; 95% CI: 1.8-15.3). There was no significant increase in risk with history of hypothyroidism (OR=1.8) or hyperthyroidism (OR=1.7). For any benign thyroid disease, the OR was 6.4 (95% CI: 3.4-12.0); and the population attributable risk was about 26% (95% CI: 21.1-30.9). Stepwise regression analysis showed that high consumption of processed fish products (OR=2.2; 95% CI: 1.6-3.0) fresh fish (OR=0.5; 95% CI: 0.4-0.7) and chicken (OR=1.7; 95% CI: 1.2-2.3) were independently associated with thyroid cancer with significant dose-response relationships. Among the thyroid cancer patients who reported high consumption of fish products, a large majority also reported high consumption of fresh fish (98%) and shellfish (68%). No clear association emerged with consumption of cruciferous vegetables. These data support the hypothesis that hyperplastic thyroid disease is strongly related to thyroid cancer; and that habitual high consumption of various seafoods may be relevant to the aetiology of thyroid cancer. The association with chicken consumption requires further study.     

Family history of benign thyroid disease and cancer and risk of thyroid cancer

In a population-based study of 313 case-control pairs in Kuwait, we evaluated whether a family history of benign thyroid disease (BTD) and thyroid or other cancers was associated with an increased risk of thyroid cancer, the second most common neoplasm among women in this and several other Arab countries in the Gulf region. Family history of BTD was reported by 78 (24.9%) cases and 40 (12.8%) controls in 132 and 57 relatives, respectively. There was an approximately 2-fold increased risk of thyroid cancer in individuals who had a mother (Odds Ratio (OR)=2.3; 95% Confidence Intervals (95% CI): 1.1-5.1), sister(s) (OR=2.6; 95% CI: 1.3-5.3) or aunt(s) (OR=2.1; 95% CI: 0.9-5.3) with BTD; there was also a significant trend in increasing risk with an increasing number of affected female relatives (P<0.0001). Stratification by age at diagnosis of the case showed that individuals aged 相似文献   

Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.     

Do thyroid disorders increase the risk of breast cancer?

The objective of this study was to determine whether thyroid disorders or treatment of such disorders affects the risk of breast cancer. Subjects aged 35-64 years were participants in the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study, a population-based, case-control study of invasive breast cancer that was carried out at five sites in the United States. In-person interviews were completed for 4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682 control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression methods. Models included adjustment for age (5-year age groups), race (white or black), and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9-1.2) was not associated with breast cancer risk. Only women with a history of thyroid cancer had an increased risk, but this was restricted to parous women (parous OR = 3.4, 95% CI = 1.5-8.1; nulliparous OR = 0.5, 95% CI = 0.04-5.1). Breast cancer risk was not associated with treatment for thyroid disorders. There was no statistical interaction between thyroid disorders, thyroid treatments, and race, menopausal status, or parity. We found no association between thyroid disorders or their associated treatments and 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.     

Differences in breast cancer risk factors by tumor marker subtypes among premenopausal Vietnamese and Chinese women.

We evaluated associations between reproductive and lifestyle risk factors with breast cancer tumor marker status in a case-control study. Cases were premenopausal women living in Vietnam and China who were eligible for a clinical trial of oophorectomy and tamoxifen as treatment for breast cancer (n = 682). Controls were nonrelative hospital visitors, matched on age to the cases (n = 649). Immunohistochemical analysis was used to identify the presence of estrogen receptor (ER) and progesterone receptor and the overexpression of HER-2/neu oncogene. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression, adjusted for known confounders. Overall, 280 (61%) tumor samples were ER positive and 176 (38%) were ER negative. HER-2/neu overexpression was detected in 161 (35%) samples, whereas 286 (26%) samples were HER-2/neu negative. We observed an inverse trend between increasing parity and decreasing breast cancer risk (P = 0.002). Women ages > or =25 years at first birth had increased breast cancer risk compared with women ages <25 years at first birth (OR, 1.53; 95% CI, 1.20-1.95). Women who consumed alcohol had increased risk of breast cancer compared with women who did not (OR,1.85; 95% CI, 1.32-2.61). Compared with controls, OR estimates for breast cancer by parity and age at first birth were significantly associated with ER and/or HER-2/neu tumor status by Wald test (P < 0.05). Family history, age at menarche, cumulative lactation, body mass index, and education were not significantly related to breast cancer risk. Our findings support the hypothesis that some breast cancer risk factors differ by ER and HER-2/neu tumor marker subtypes.     

Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger

Differences in incidence, prognosis, and treatment response suggest gene expression patterns may discern breast cancer subtypes with unique risk factor profiles; however, previous results were based predominantly on older women. In this study, we examined similar relationships in women ≤ 56 years, classified by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 for 890 breast cancer cases and 3,432 frequency-matched population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) for tumor subtypes were calculated using multivariate polytomous regression models. A total of 455 (51.1%) tumors were considered luminal A, 72 (8.1%) luminal B, 117 (13.1%) non-luminal HER-2/neu+, and 246 (27.6%) triple negative. Triple negative tumors were associated with breast feeding duration (per 6 months: OR = 0.76, 95% CI 0.64-0.90). Among premenopausal women, increasing body size was more strongly associated with luminal B (OR = 1.73, 95% CI 1.07-2.77) and triple negative tumors (OR = 1.67, 95% CI 1.22-2.28). A history of benign breast disease was associated only with increased risk of luminal A tumors (OR = 1.89, 95% CI 1.43-2.50). A family history of breast cancer was a risk factor for luminal A tumors (OR = 1.93, 95% CI 1.38-2.70) regardless of age, and triple negative tumors with higher risks for women <45 (OR = 5.02, 95% CI 2.82-8.92; P for age interaction = 0.005). We found that little-to-no breastfeeding and high BMI were associated with increased risk of triple negative breast cancer. That some risk factors differ by molecular subtypes suggests etiologic heterogeneity in breast carcinogenesis among young women.     

Tubal ligation,hysterectomy and epithelial ovarian cancer in the New England Case–Control Study

Previous studies have observed that tubal ligation and hysterectomy are associated with a decreased risk of ovarian cancer; however, little is known about whether these associations vary by surgical characteristics, individual characteristics or tumor histology. We used logistic regression to examine tubal ligation, simple hysterectomy and hysterectomy with unilateral oophorectomy in relation to risk of epithelial ovarian cancer in the New England Case–Control Study. Our primary analysis included 2,265 cases and 2,333 controls. Overall, tubal ligation was associated with a lower risk of epithelial ovarian cancer [odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.68–0.97], especially for endometrioid tumors (OR = 0.45, 95% CI: 0.29–0.69). The inverse association between tubal ligation and ovarian cancer risk was stronger for women who had undergone the procedure at the time of last delivery (OR = 0.60, 95% CI: 0.42–0.84) rather than at a later time (OR = 0.93, 95% CI: 0.75–1.15). Overall, simple hysterectomy was not associated with ovarian cancer risk (OR: 1.09, 95% CI: 0.83–1.42), although it was associated with a nonsignificant decreased risk of ovarian cancer among women who underwent the procedure at age 45 or older (RR: 0.64, 95% CI: 0.40–1.02) or within the last 10 years (OR = 0.65, 95% CI: 0.38–1.13). Overall, women who had a hysterectomy with a unilateral oophorectomy had significantly lower risk of ovarian cancer (OR = 0.65, 95% CI: 0.45–0.94). In summary, tubal ligation and hysterectomy with unilateral oophorectomy were inversely associated with ovarian cancer risk in a large population‐based case–control study. Additional research is necessary to understand the potential biologic mechanisms by which these procedures may reduce ovarian cancer risk.     

Use of Exogenous Hormones and Risk of Papillary Thyroid Cancer (Washington, United States)

Objectives: Greater incidence of thyroid cancer in women than men, particularly evident during the reproductive years, has led to the suggestion that female hormones may increase risk of this disease. We conducted a population-based case-control study in women aged 18 to 64 years in three counties of western Washington State (United States) to assess the relation of use of exogenous hormones, including oral contraceptives (OC) and hormone replacement therapy (HRT), to risk of papillary thyroid cancer.Methods: Of 558 women with thyroid cancer of the follicular epithelium diagnosed during 1988-94 who were identified as eligible, 468 (83.9 percent) were interviewed; this analysis was restricted to women with papillary histology (n = 410). Controls (n = 574) were identified by random digit dialing, with a response proportion of 73.6 percent. Logistic regression was used to calculate odds ratios (OR) and associated 95 percent confidence intervals (CI) estimating the relative risk of papillary thyroid cancer among users of exogenous hormones.Results: Among women aged 45 to 64 years, we observed no association of use of OCs or HRT with risk of papillary thyroid cancer. Among women less than 45 years of age, risk of papillary thyroid cancer was reduced in women who had ever used OCs (OR = 0.6, CI = 0.4-0.9); beyond the relation with ever-use, there was no further association with specific aspects of exposure such as estrogenic potency, latency, recency, age at first or last use, or use at the reference date.Conclusions: Our data do not support the hypothesis that use of exogenous estrogens increases the risk of female thyroid cancer. Cancer Causes and Control 1998, 9, 341-349     

Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update

Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80%, and following the first diagnosis the 10-year risk of contralateral breast cancer is approximately 30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27-0.65).     

DNA methylation in benign breast epithelium in relation to age and breast cancer risk.

BACKGROUND: Many established breast cancer risk factors are related to the timing and duration of exposure to reproductive hormones, which are known to drive breast epithelial cell proliferation. The epigenetic molecular clock hypothesis suggests that CpG island methylation records the cell division history of benign epithelium. In proliferative epithelium, such as breast, this may provide an individualized cell-based measure of cancer risk. METHODS: Methylation of cyclin D2, APC, HIN1, RASSF1A, and RAR-beta2 was measured by quantitative multiplex methylation-specific PCR in 290 benign and malignant breast epithelial cell samples obtained by palpation-directed fine-needle aspiration biopsy from 164 women. Univariate, multivariate, and unsupervised cluster analysis was used to establish the relationship between TSG methylation and a personal history of breast cancer, predicted breast cancer risk, and specific breast cancer risk factors. RESULTS: RASSF1A methylation was highly correlated with breast cancer risk [odds ratio (OR), 5.28; 95% confidence interval (95% CI), 1.95-14.32; P = 0.001], atypical cytology (OR, 4.11; 95% CI, 1.30-12.98; P = 0.016), and benign breast disease requiring biopsy (OR, 6.12; 95% CI, 1.41-26.51; P = 0.016). RASSF1A methylation increased linearly between ages 32 and 55. Increasing parity was associated with decreased APC methylation. CONCLUSIONS: TSG methylation increases in benign breast epithelium with increasing age. Because it is independently related to a personal history of benign or malignant breast disease and to predicted breast cancer risk, it may have value for breast cancer risk stratification and as a surrogate endpoint marker in prevention trials.     

Family history and risk of breast cancer in hispanic and non-hispanic women: the New Mexico Women's Health Study

Objectives: Many epidemiologic studies have demonstrated that an increased risk of breast cancer is associated with positive family history of this disease. Little information had been available on the relationship of breast cancer risk with family history in Hispanic women. To investigate the association of family history of breast cancer on the risk of breast cancer, we examined the data from the New Mexico Women's Health Study (NMWHS), a statewide case–control study. Methods: In this study 712 women (332 Hispanics and 380 non-Hispanic whites) with breast cancer and 844 controls (388 Hispanics and 456 non-Hispanic whites) were included. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI), adjusted for sociodemographic, medical, and reproductive factors. Results: We found an increased risk in women with a history of breast cancer in one or more first-degree or second-degree relatives (OR = 1.5, 95% CI 1.2–1.9), first-degree relatives (OR = 1.3, 95% CI 1.0–1.8) and second-degree relatives (OR = 1.6, 95% CI 1.2–2.2). Hispanic women had higher risk estimates for a positive family history (OR = 1.7, 95% CI 1.1–2.5) than non-Hispanic white women (OR = 1.4, 95% CI 1.0–2.0); however, the differences were not statistically significant. In both ethnic groups a higher risk was observed in premenopausal women compared with postmenopausal women and women diagnosed with breast cancer before age 50years compared with older women. Conclusions: The results indicate that Hispanic women with a family history of breast cancer are at increased risk of breast cancer.     

Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project

The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women.     

Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico.

A case-control study was carried out in Mexico City during 1995-1997 among women with epithelial ovarian cancer (84 cases) and endometrial cancer (85 cases). The control group consisted of 668 healthy women, matched according to age categories. In a multivariate analysis, the reproductive risk factors for ovarian and endometrial cancer are similar. The risk of ovarian cancer was inversely related to the number of full-term pregnancies; the odds ratio (OR) was 0.17 and the 95% confidence interval (CI) was 0.05-0.54 when comparing nulliparous women versus those with more than seven pregnancies. For endometrial cancer, a similar association was observed (OR, 0.11; 95% CI, 0.04-0.34). The use of oral contraceptive hormones was inversely associated with both ovarian (OR, 0.36; 95% CI, 0.15-0.83) and endometrial cancer risk (OR, 0.36; 95% CI, 0.14-0.90). In women with a history of more than 8.7 years without ovulation, the risk of ovarian cancer decreased four times (OR, 0.23; 95% CI, 0.10-0.50), and that of endometrial cancer decreased more than five times (OR, 0.17; 95% CI, 0.08-0.35). These two neoplasms are clearly typified as hormone dependent, and it is possible to establish that "ovulation" and "exfoliative" mechanisms jointly determine the level of risk for both ovarian and endometrial cancer.     

Association between lifestyle,menstrual/reproductive history,and histological factors and risk of breast cancer in women biopsied for benign breast disease

Purpose

Women with benign breast disease (BBD) have an increased risk of subsequent breast cancer. However, whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD is unclear. In this study, we investigated the associations of lifestyle, menstrual/reproductive, and histological factors with risk of breast cancer among women biopsied for BBD.

Methods

We conducted a case–control study, nested within a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest between 1971 and 2006. Cases were women who developed a subsequent invasive breast cancer during follow-up; controls were individually matched to cases on age at BBD diagnosis. A total of 526 case–control pairs were included in the study. We calculated crude and multivariable OR and 95% CI for the associations between lifestyle, menstrual/reproductive, and histological factors and breast cancer risk using conditional logistic regression.

Results

Compared to premenopausal women, postmenopausal women had reduced risk of subsequent breast cancer (OR 0.60; 95% CI 0.39–0.94), whereas women who ever used hormone replacement therapy (HRT) had increased risk (OR 3.61; 95% CI 1.68–7.75), as did women whose BBD lesion showed atypical hyperplasia (OR 5.56; 95% CI 2.05–15.06). Smoking, BMI, early menarche, multiparity (≥4), history of oophorectomy, and extent of lobular involution were not associated with risk of breast cancer.

Conclusion

This study suggests that use of HRT and having atypical hyperplasia are associated with increased risk of breast cancer among women with BBD, while postmenopausal women with BBD have a reduced risk.

     

Selected medical conditions and risk of breast cancer.

Several diseases are known or suspected to be associated with altered levels of hormones and growth factors that may influence breast cancer risk. To elucidate this possibility, we studied the relationship between 23 medical conditions or procedures and breast cancer risk by means of data from a multicentric case-control study conducted between 1991 and 1994 in six Italian areas. The study included 2569 histologically confirmed incident cases of breast cancer (median age 55 years, range 23-74 years) and 2588 control women (median age 56 years, range 20-74 years) admitted to the same hospitals as cases for a variety of acute conditions unrelated to known or suspected risk factors for breast cancer. After allowance for education, parity and body mass index, elevated odds ratios (ORs) emerged for history of diabetes mellitus in post-menopausal women (OR = 1.5, 95% CI 1.1-2.0), hypertension in pregnancy (OR = 1.8, 95% CI 1.0-3.4) and breast nodules (OR = 1.3, 95% CI 1.0-1.7). Risk decreases were associated with ovarian ablation for ovarian cysts (OR = 0.5, 95% CI 0.3-0.7) and with thyroid nodules (OR = 0.7, 95% CI 0.5-0.9) but not with the combination of any type of benign thyroid disease. While most examined conditions seemed unrelated to breast cancer risk, the association with late-onset diabetes is of special interest as it suggests a role of hyperinsulinaemia and insulin resistance in breast cancer promotion. It also points to preventive lifestyle modifications.     

Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers.

BACKGROUND: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. METHODS: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. RESULTS: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0. 28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. CONCLUSIONS: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.     

Risk Factors for breast cancer among japanese women: A case-control study in Ibaraki, Japan

BACKGROUND: The number of epidemiologic studies on breast cancer risk factorsin Japanese women is still quite limited. Our objective was to clarify the relationship between lifestyle, body size and breast cancer risk. METHODS: A matched case-control study was conducted in Ibaraki, Japan. The participants were 148 women aged 26-69 diagnosed with breast cancer at Tsukuba University Hospital or Tsukuba Medical Center Hospital between January, 1990 and March, 1997. Two controls were individually matched to the cases by age and residence. A self-administered questionnaire was used to obtain information on the family history of breast cancer, reproductive history, education, body size and lifestyle factors. Conditional logistic regression analysis was used to estimate oddsratios (ORs)and 95% confidence intervals (95% CI). RESULTS: After adjustment for potential confounders, heavy weight and higher body mass index were associated with an increased risk of breast cancer among postmenopausal women (OR = 1.76, 95% CI = 0.69, 4.48; OR = 1.57, 95% CI=0.61, 3.99, respectively). Current or ex-smokers were found to be at an increased risk for breast cancer (OR = 3.33; 95% CI = 1.63, 6.80). Women who take hot baths had a decreased risk for breast cancer (OR = 0.67; 95% CI = 0.43, 1.06). Recreational physical activity was associated with a reduced risk of breast cancer (PTrend = 0.005).OR for breast cancer among physically active women was 0.36 (95% CI = 0.19, 0.70), as compared with inactive women. Taller women had an increased risk of breast cancer relative to shorter women (OR = 1.49; 95% CI = 0.83, 2.70). No significant association between alcohol consumption and breast cancer risk was detected. CONCLUSION: Our results suggest that several potentially modifiable lifestyle factors may be useful for the prevention of breast cancer.     

A pooled analysis of case-control studies of thyroid cancer ¶II. Menstrual and reproductive factors

Objective: It has been suggested that female hormones, and hence menstrual and reproductive factors, play a role in thyroid cancer etiology. Epidemiological data, however, are limited and inconsistent, partly because of the small number of cases included in each study. To clarify the etiology of thyroid cancer, we conducted a pooled analysis of original data from 14 case-control studies, 4 from the United States, 2 from Asia, and 8 from Europe.Methods: This analysis included a total of 2,247 female cases of thyroid cancer (80% papillary) and 3,699 control women. Pooled odds ratios (OR) were estimated using logistic regression, conditioning on study and (i) matching sets for individually matched studies, or (ii) quinquennia of age for the other studies. Additional terms for age and history of radiation exposure were included in the regression equations.Results: The OR per year of later menarche was 1.04 (95% confidence interval (CI) 1.0–1.1). Compared to pre-menopausal women, the OR was 1.3 for women with natural menopause, and 1.8 for those with artificial menopause, but the studies were heterogeneous and the association may be due, at least in part, to diagnostic or ascertainment bias. Parity, spontaneous or induced abortions and history of infertility were not associated with thyroid cancer risk. The OR was above unity in women reporting later age at first birth (OR=1.1, 95% CI 1.0–1.3 for 5-year delay) and higher in the first years after a birth.Conclusions: The associations of menstrual and reproductive factors with thyroid cancer risk were generally weak, but appeared stronger among women diagnosed with thyroid cancer at younger ages.