Despite the increasing incidence of thyroid cancer, there is limited information on its etiology. The strikingly higher rates in young women, compared to men, suggest that sex steroid hormones may be involved in the development of this disease.
We investigated the effects of menstrual, reproductive, and other hormonal factors on papillary thyroid cancer risk in the prospective California Teachers Study (CTS) cohort. Among 117,646 women, 233 were diagnosed with invasive histologically-confirmed papillary thyroid cancer after cohort enrollment and before January 1, 2008. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models.
Among younger women (age <45 years at baseline; approximately one-third of the cohort), but not older women, later age at menarche (age ≥14 years) was associated with increased risk (RR=1.88, 95% CI: 1.13–3.13; pinteraction by age=0.06). Risk was also increased among young women who had longer (>30 days) adolescent menstrual cycles (RR=1.78, 95% CI: 1.01–3.14) and whose last pregnancy had ended within five years of cohort enrollment (RR=2.21, 95% CI: 1.13–4.34). Among older women (age ≥45 years at baseline), ever use of estrogen-only therapy was associated with a statistically non-significant increase in risk (RR=1.69, 95% CI: 0.95–2.98).
The findings from this prospective analysis suggest that several factors related to delayed pubertal development and the transient effects of pregnancy may be particularly important in influencing risk in young women.
These results suggest the importance of future research into the role of progesterone and the estrogen-to-progesterone ratio.
papillary thyroid cancer; menstrual factors; reproductive factors; exogenous hormone use; epidemiology
Overall, the incidence of papillary thyroid cancer in Hispanic women residing in the United States (US) is similar to that of non-Hispanic white women. However, little is known as to whether rates in Hispanic women vary by nativity, which may influence exposure to important risk factors.
Nativity-specific incidence rates among Hispanic women were calculated for papillary thyroid cancer using data from the California Cancer Registry (CCR) for the period 1988–2004. For the 35% of cases for whom birthplace information was not available from the CCR, nativity was statistically imputed based on age at Social Security number issuance. Population estimates were extracted based on US Census data. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were also estimated.
In young (age <55 years) Hispanic women, the incidence of papillary thyroid cancer among US-born (10.65 per 100,000) was significantly greater than that for foreign-born (6.67 per 100,000; IRR=1.60, 95% CI: 1.44–1.77). The opposite pattern was observed in older women. The age-specific patterns showed marked differences by nativity: among foreign-born, rates increased slowly until age 70 years, whereas, among US-born, incidence rates peaked during the reproductive years. Incidence rates increased over the study period in all subgroups.
Incidence rates of papillary thyroid cancer vary by nativity and age among Hispanic women residing in California. These patterns can provide insight for future etiologic investigations of modifiable risk factors for this increasingly common and understudied cancer.
papillary thyroid cancer; incidence rates; nativity; Hispanic women; cancer surveillance
Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies.
We analyzed primary data from 14 prospective cohort studies that included 319 716 men and 542 948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided.
During 7–20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, Ptrend = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, Ptrend = .90). No between-study heterogeneity was observed (for dietary folate, Pheterogeneity = .15; for total folate, Pheterogeneity = .22).
Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.
Adult body size has long been known to influence breast cancer risk, and there is now increasing evidence that childhood and adolescent body size may also play a role.
We assessed the association with body size at ages 10, 15, and 20 years in 475 premenopausal and 775 postmenopausal Hispanic women who participated in a population-based case-control study of breast cancer conducted from 1995 to 2004 in the San Francisco Bay Area. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations with self-reported relative weight compared to peers and body build at ages 10, 15, and 20 years.
In premenopausal women, we found inverse associations with relative weight compared to peers, with ORs of 0.63 (Ptrend = 0.05), 0.31 (Ptrend < 0.01), and 0.44 (Ptrend = 0.02) for heavier vs. lighter weight at ages 10, 15, and 20 years, respectively. These inverse associations were stronger in currently overweight women and US-born women and did not differ significantly for case groups defined by estrogen receptor status. Inverse associations were stronger in US-born than foreign-born Hispanics. In postmenopausal women not currently using hormone therapy, inverse associations with relative weight were limited to US-born Hispanics.
Large body size at a young age may have a long-lasting influence on breast cancer risk in premenopausal, and possibly postmenopausal, Hispanic women that is independent of current BMI.
These findings need to be weighed against adverse health effects associated with early-life obesity.
Adolescence; BMI; body size; breast cancer; estrogen receptor
Epidemiologic studies of pancreatic cancer risk have reported null or non-significant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently.
A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model.
Compared to individuals with a body mass index (BMI) at baseline between 21–22.9kg/m2, pancreatic cancer risk was 47% higher (95%CI:23–75%) among obese (BMI≥30kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI=1.09–1.56 comparing BMI≥25kg/m2 to a BMI between 21–22.9kg/m2). Compared to individuals who were not overweight in early adulthood (BMI<25kg/m2) and not obese at baseline (BMI<30kg/m2), pancreatic cancer risk was 54% higher (95%CI=24–93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≥10kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR=1.35 comparing the highest versus lowest quartile, 95%CI=1.03–1.78).
BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.
Pancreatic Cancer; Anthropometry; Pooled Analysis
To investigate how birthplace influences the incidence of papillary thyroid cancer among Asian American women.
Birthplace- and ethnic-specific age-adjusted and age-specific incidence rates were calculated using data from the California Cancer Registry for the period 1988–2004. Birthplace was statistically imputed for 30% of cases using a validated imputation method based on age at Social Security number issuance. Population estimates were obtained from the US Census. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated for foreign-born vs. US-born women.
Age-adjusted incidence rates of papillary thyroid cancer among Filipina (13.7 per 100,000) and Vietnamese (12.7) women were more than double those of Japanese women (6.2). US-born Chinese (IRR=0.48, 95% CI: 0.40–0.59) and Filipina women (IRR=0.74, 95% CI: 0.58–0.96) had significantly higher rates than those who were foreign-born; the opposite was observed for Japanese women (IRR=1.55, 95% CI: 1.17–2.08). The age-specific patterns among all foreign-born Asian women and US-born Japanese women showed a slow steady increase in incidence until age 70. However, among US-born Asian women (except Japanese), substantially elevated incidence rates during the reproductive and menopausal years were evident.
Ethnic- and birthplace-variation in papillary thyroid cancer incidence can provide insight into the etiology of this increasingly common and understudied cancer.
papillary thyroid cancer; incidence rates; birthplace; Asian American women; cancer surveillance
We examined whether dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or specific foods rich in these compounds is associated with reduced risk of B-cell non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or Hodgkin lymphoma (HL) in a large, prospective cohort of women.
Between 1995-1996 and December 31, 2007, among 110,215 eligible members of the California Teachers Study cohort, 536 women developed incident B-cell NHL, 104 developed MM, and 34 developed HL. Cox proportional hazards regression, with age as the time-scale, was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for risk of lymphoid malignancies.
Weak inverse associations with risk of diffuse large B-cell lymphoma were observed for isothiocyanates (RR for ≥12.1 vs. <2.7 mcM/day=0.67, 95% CI: 0.43-1.05) and an antioxidant index measuring hydroxyl radical absorbance capacity (RR for ≥2.2 vs. <0.9 μM Trolox equiv/g/day=0.68, 95% CI: 0.42-1.10; ptrend=0.08). Risk of other NHL subtypes, overall B-cell NHL, MM, or HL was not generally associated with dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or major food sources of these compounds.
Isoflavones, lignans, isothiocyanates, and antioxidant compounds are not associated with risk of most B-cell malignancies, but some phytocompounds may decrease risk of selected subtypes.
lymphoma; diet; isothiocyanates; antioxidants; cohort studies
Large body size has been associated with a reduced risk of premenopausal breast cancer in non-Hispanic white women. Data on other racial/ethnic populations are limited. The authors examined the association between premenopausal breast cancer risk and adult body size in 672 cases and 808 controls aged ≥35 years from a population-based case-control study conducted in 1995–2004 in the San Francisco Bay Area (Hispanics: 375 cases, 483 controls; African Americans: 154 cases, 160 controls; non-Hispanic whites: 143 cases, 165 controls). Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. Height was associated with increased breast cancer risk (highest vs. lowest quartile: odds ratio = 1.77, 95% confidence interval: 1.23, 2.53; Ptrend < 0.01); the association did not vary by hormone receptor status or race/ethnicity. Body mass index (measured as weight (kg) divided by height (m) squared) was inversely associated with risk in all 3 racial/ethnic groups, but only for estrogen receptor– and progesterone receptor–positive tumors (body mass index ≥30 vs. <25: odds ratio = 0.42; 95% confidence interval: 0.29, 0.61). Other body size measures (current weight, body build, adult weight gain, young adult weight and body mass index, waist circumference, and waist-to-height ratio) were similarly inversely associated with risk of estrogen receptor– and progesterone receptor–positive breast cancer but not estrogen receptor– and progesterone receptor–negative disease. Despite racial/ethnic differences in body size, inverse associations were similar across the 3 racial/ethnic groups when stratified by hormone receptor status.
African Americans; body size; breast neoplasms; Hispanic Americans; premenopause; receptors, estrogen; receptors, progesterone
Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995–1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18–22 years, at ages 30–35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.
alcohol drinking; cohort studies; lymphoma, non-Hodgkin; multiple myeloma
The role of moderate physical activity and life patterns of activity in reducing endometrial cancer risk remains uncertain.
We assessed lifetime histories of activity from recreation, transportation, chores, and occupation and other risk factors in a population-based case-control study of endometrial cancer conducted in the San Francisco Bay area. The analysis was based on 472 newly diagnosed cases ascertained by the regional cancer registry and 443 controls identified by random-digit dialing who completed an in-person interview.
Reduced risks associated with greater lifetime physical activity (highest vs. lowest tertile) were found for both total activity (odds ratio (OR) = 0.61 (95% confidence interval (CI) = 0.43–0.87, ptrend = 0.01) and activity of moderate intensity (OR=0.44, 95% CI=0.30–0.64, ptrend < 0.0001). Compared to women with low lifetime physical activity (below median), those with greater activity throughout life had the highest reduction in risk (OR=0.62, 95% CI=0.44–0.88). Inverse associations were stronger in obese and overweight women, but differences were not statistically significantly different from those in normal weight women.
These findings suggest that physical activity in adulthood, even of moderate intensity, may be effective in lowering the risk of endometrial cancer, particularly among those at highest risk for this disease.
The results emphasize the importance of evaluating lifetime histories of physical activity from multiple sources, including both recreational and non-recreational activities of various intensities, in order to fully understand the relation between physical activity and disease risk.
Physical activity; exercise; endometrial cancer; corpus uteri
To investigate whether hormone therapy (HT) and obesity are associated with endometrial cancer risk among postmenopausal women in the California Teachers Study cohort.
Of 28,418 postmenopausal women, 395 developed type 1 endometrial cancer between 1995 and 2006. Multivariate Cox regression was performed to estimate relative risks (RR), stratified by HT use (never used, ever estrogen-alone (ET), or exclusively estrogen-plus-progestin (EPT)).
Among women who never used HT, overall and abdominal adiposity were associated with increased risk; when evaluated simultaneously, abdominal adiposity was more strongly associated (RR 2.2, 95% confidence interval (CI): 1.1–4.5 for waist ≥35 vs. <35 inches). Among women who ever used ET, risk was increased in women with BMI ≥25 kg/m2 (RR 1.6, 95% CI: 1.1–2.3 vs. <25 kg/m2). Neither overall nor abdominal obesity was associated with risk in women who exclusively used EPT (P-interaction<0.001 for BMI by HT use).
Among women who never used HT, risk was strongly positively related to obesity and may have been influenced more by abdominal than overall adiposity; however, due to small numbers, this latter finding requires replication. Among women who ever used ET, being overweight at baseline predicted higher risk, whereas use of EPT mitigated any effect of obesity.
endometrial cancer; obesity; abdominal adiposity; hormone therapy
Background: It is well established that estrogen increases endometrial cancer risk, whereas progesterone opposes the estrogen effects. The PROGINS allele of the progesterone receptor (PGR) gene reduces the function of PGR and has been associated with increased risk of the endometrioid type ovarian cancer. We investigated whether genetic variation in PGR is also associated with endometrial cancer risk using a haplotype-based approach. Methods: We pooled data from two endometrial cancer case–control studies that were nested within two prospective cohorts, the Multiethnic Cohort Study and the California Teachers Study. Seventeen haplotype-tagging single nucleotide polymorphisms (SNPs) across four linkage disequilibrium (LD) blocks spanning the PGR locus were genotyped in 583 incident cases and 1936 control women. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each haplotype were estimated using conditional logistic regression, stratified by age and ethnicity. Results: Genetic variation in LD block 3 of the PGR locus was associated with endometrial cancer risk (Pglobal test = 0.002), with haplotypes 3C, 3D and 3F associated with 31–34% increased risk. Among whites (383 cases/840 controls), genetic variation in all four blocks was associated with increased endometrial cancer risk (Pglobal test = 0.010, 0.013, 0.005 and 0.020). Haplotypes containing the PROGINS allele and several haplotypes in blocks 1, 3 and 4 were associated with 34–77% increased risk among whites. SNP analyses for whites suggested that rs608995, partially linked to the PROGINS allele (r2 = 0.6), was associated with increased risk (OR = 1.30, 95% CI = 1.06–1.59). Conclusions: Our results suggest that genetic variation in the PGR region is associated with endometrial cancer risk.
We estimated trends in breast cancer incidence rates for specific Asian populations in California to determine if disparities exist by immigrant status and age.
To calculate rates by ethnicity and immigrant status, we obtained data for 1998 through 2004 cancer diagnoses from the California Cancer Registry and imputed immigrant status from Social Security Numbers for the 26% of cases with missing birthplace information. Population estimates were obtained from the 1990 and 2000 US Censuses.
Breast cancer rates were higher among US- than among foreign-born Chinese (incidence rate ratio [IRR] = 1.84; 95% confidence interval [CI] = 1.72, 1.96) and Filipina women (IRR = 1.32; 95% CI=1.20, 1.44), but similar between US- and foreign-born Japanese women. US-born Chinese and Filipina women who were younger than 55 years had higher rates than did White women of the same age. Rates increased over time in most groups, as high as 4% per year among foreign-born Korean and US-born Filipina women. From 2000–2004, the rate among US-born Filipina women exceeded that of White women.
These findings challenge the notion that breast cancer rates are uniformly low across Asians and therefore suggest a need for increased awareness, targeted cancer control, and research to better understand underlying factors.
The female sex steroids estrogen and progesterone are important in breast cancer etiology. It therefore seems plausible that variation in genes involved in metabolism of these hormones may affect breast cancer risk, and that these associations may vary depending on menopausal status and use of hormone therapy.
We conducted a nested case-control study of breast cancer in the California Teachers Study cohort. We analyzed 317 tagging single nucleotide polymorphisms (SNPs) in 24 hormone pathway genes in 2746 non-Hispanic white women: 1351 cases and 1395 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by fitting conditional logistic regression models using all women or subgroups of women defined by menopausal status and hormone therapy use. P values were adjusted for multiple correlated tests (PACT).
The strongest associations were observed for SNPs in SLCO1B1, a solute carrier organic anion transporter gene, which transports estradiol-17β-glucuronide and estrone-3-sulfate from the blood into hepatocytes. Ten of 38 tagging SNPs of SLCO1B1 showed significant associations with postmenopausal breast cancer risk; 5 SNPs (rs11045777, rs11045773, rs16923519, rs4149057, rs11045884) remained statistically significant after adjusting for multiple testing within this gene (PACT = 0.019-0.046). In postmenopausal women who were using combined estrogen-progestin therapy (EPT) at cohort enrollment, the OR of breast cancer was 2.31 (95% CI = 1.47-3.62) per minor allele of rs4149013 in SLCO1B1 (P = 0.0003; within-gene PACT = 0.002; overall PACT = 0.023). SNPs in other hormone pathway genes evaluated in this study were not associated with breast cancer risk in premenopausal or postmenopausal women.
We found evidence that genetic variation in SLCO1B1 is associated with breast cancer risk in postmenopausal women, particularly among those using EPT.
Estrogen alone therapy (ET) or estrogen and progestin (EPT) as menopausal hormone therapy (HT) has been commonly used to alleviate menopausal symptoms. Treatments containing ≥10 days/month (d/m) of progestin are considered relatively safe with respect to endometrial cancer risk. However, the endometrial safety of long-term EPT regimens is uncertain.
We conducted a case-control study of 311 invasive endometrial cancer cases and 570 controls nested within the California Teachers Study cohort. We used unconditional logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (95%CIs) for the association between long term HT use and endometrial cancer risk and to assess the modifying effect of body mass index (BMI).
Long-term (≥ 10 years) use of ET, sequential EPT with < 10 d/m progestin, and continuous-combined EPT (≥ 25 d/m progestin) were all associated with an elevated risk of endometrial cancer (OR: 4.5; 95%CI: 2.5–8.1, OR: 4.4, 95%CI: 1.7–11.2, and OR: 2.1; 95%CI: 1.3–3.3, respectively; all P for trend < .0001). Risk associated with short-term use was elevated only for ET preparations. The association for continuous-combined EPT was confined to thinner women (BMI < 25 kg/m2) (P for interaction: 0.03). Among heavier women (BMI ≥ 25 kg/m2), use of continuous-combined EPT was associated with a statistically nonsignificant reduction in risk.
These findings confirm that long-term use of ET, sequential EPT, or, among normal weight women, continuous-combined EPT is associated with increased risk of endometrial cancer.
Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22–84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61–1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.
body mass index; body size; cohort studies; exercise; hip; lymphoma, non-Hodgkin; waist-hip ratio
Obesity is a risk factor for asthma, particularly in women, but few cohort studies have evaluated abdominal obesity, which reflects metabolic differences in visceral fat known to influence systemic inflammation. We examined the relationships of asthma prevalence with measures of abdominal obesity and adult weight gain, in addition to body mass index (BMI), in a large cohort of female teachers. We calculated prevalence odds ratios (ORs) for current asthma using multivariable linear modeling, adjusting for age, smoking, and race/ethnicity. Of the 88,304 women in the analyses, 13% (11,500) were obese (BMI ≥ 30 kg/m2) at baseline; 1,334 were extremely obese (BMI ≥ 40). Compared to those of normal weight, the adjusted OR for adult-onset asthma increased from 1.40 (95% confidence interval (CI): 1.31, 1.49) for overweight women to 3.30 (95% CI: 2.85, 3.82) for extremely obese women. Large waist circumference (> 88 cm) was associated with increased asthma prevalence even among women with a normal BMI (OR = 1.37, 95% CI: 1.18, 1.59). Among obese women, the OR for asthma was greater among those who were also abdominally obese compared to women whose waist was ≤ 88 cm (2.36 vs. 1.57). Obese and overweight women were at greater risk of severe asthma episodes, measured by urgent medical visits and hospitalizations. This study confirms the association between excess weight and asthma severity and prevalence, and showed that a large waist was associated with increased asthma prevalence even among women considered to have normal body weight.
Asthma; Body Fat Distribution; Body Mass Index; Cohort Studies; Obesity; Prevalence
Contralateral second primary breast cancers occur in 4% of female breast cancer survivors. Little is known about differences in risk for second primary breast cancers related to the estrogen and progesterone receptor (hormone receptor [HR]) status of the first tumor.
We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for contralateral primary breast cancers among 4927 women diagnosed with a first breast cancer between January 1, 1992, and December 31, 2004, using the National Cancer Institute’s Surveillance, Epidemiology, and End Results database.
For women whose first breast tumors were HR positive, risk of contralateral primary breast cancer was elevated, compared with the general population, adjusted for age, race, and calendar year (SIR = 2.22, 95% CI = 2.15 to 2.29, absolute risk [AR] = 13 cases per 10 000 person-years [PY]), and was not related to the HR status of the second tumor. For women whose first breast tumors were HR negative, the risk of a contralateral primary tumor was statistically significantly higher than that for women whose first tumors were HR positive (SIR = 3.57, 95% CI = 3.38 to 3.78, AR = 18 per 10 000 PY), and it was associated with a much greater likelihood of an HR-negative second tumor (SIR for HR-positive second tumors = 1.94, 95% CI = 1.77 to 2.13, AR = 20 per 10 000 PY; SIR for HR-negative second tumors = 9.81, 95% CI = 9.00 to 10.7, AR = 24 per 10 000 PY). Women who were initially diagnosed with HR-negative tumors when younger than 30 years had greatly elevated risk of HR-negative contralateral tumors, compared with the general population (SIR = 169, 95% CI = 106 to 256, AR = 77 per 10 000 PY). Incidence rates for any contralateral primary cancer following an HR-negative or HR-positive tumor were higher in non-Hispanic blacks, Hispanics, and Asians or Pacific Islanders than in non-Hispanic whites.
Risk for contralateral second primary breast cancers varies substantially by HR status of the first tumor, age, and race and/or ethnicity. Women with HR-negative first tumors have nearly a 10-fold elevated risk of developing HR-negative second tumors, compared with the general population. These findings warrant intensive surveillance for second breast cancers in women with HR-negative tumors.
Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear.
Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia.
Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend < 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors.
These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration.
We investigated the association between hypertension, antihypertensive (AH) medication use, and breast cancer in a large prospective study, the California Teachers Study (CTS).
Information on history of hypertension and lifetime regular use of AH medications was collected from 114,549 women in 1995–1996. Among them, 4,151 invasive breast cancers were diagnosed between 1995 and 2006. Additional information on AH use was collected from 73,742 women in 2000–2001, and 1,714 of these women were subsequently diagnosed with breast cancer. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for breast cancer.
Use of AH medication for ≥5 years, when compared with no use, was associated with a modest increased risk of invasive breast cancer (RR = 1.18, 95%CI 1.02–1.36). This increased risk appeared to be confined to estrogen receptor (ER)-positive tumors (RR = 1.21, 95%CI 1.03–1.43) and pre-/peri-menopausal women (RR = 1.58, 95%CI 1.11–2.25).
Increased risk of invasive breast cancer was observed for long-term (≥5 years) AH use, and this appeared to be confined to ER + breast cancer and younger women.
Hypertension; Breast cancer; Antihypertensive medication
endometrial cancer; epidemiology
Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk.
We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random effects model.
A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate RR =1.22, 95% CI 1.03–1.45 comparing ≥ 30 to 0 grams/day of alcohol; p-value, test for between-studies heterogeneity= 0.80). For this comparison, the positive association was only statistically significant among women although the difference in the results by gender was not statistically significant (p-value, test for interaction = 0.19). Slightly stronger results for alcohol intake were observed when we limited the analysis to cases with adenocarcinomas of the pancreas. No statistically significant associations were observed for alcohol from wine, beer, and spirits comparing intakes of ≥ 5 to 0 grams/day. A stronger positive association between alcohol consumption and pancreatic cancer risk was observed among normal weight individuals compared to overweight and obese individuals (p-value, test for interaction = 0.01).
Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day.
Alcohol; pancreatic cancer; pooled analysis
To evaluate the reproductive and lifestyle correlates of a surgically confirmed diagnosis of endometriosis or adenomyosis in a large prospective cohort.
The California Teachers Study (CTS), an ongoing prospective study of female teachers and school administrators established from the rolls of the California State Teachers Retirement System.
Diagnoses of endometriosis and adenomyosis were identified from California statewide hospital patient discharge records for CTS cohort members with no prior history of endometriosis. Women with an incident surgical diagnosis of endometriosis (n=229) or adenomyosis (n=961) were compared to disease-free women in the same age range (for endometriosis, n=43,493; for adenomyosis, n=79,495).
Main Outcome Measure(s)
Logistic regression methods were used to calculate age-adjusted and multivariable-adjusted prevalence odds ratios (POR) and associated 95 percent confidence intervals (CI) for self-reported menstrual and reproductive characteristics.
Women diagnosed with endometriosis were younger than those diagnosed with adenomyosis. Factors significantly associated with endometriosis were having a mother or sister with endometriosis and nulligravidity. Factors significantly associated with adenomyosis were increasing parity, early menarche (≤10 years of age), and having short menstrual cycles (≤24 days in length). Women who were obese were also more likely to have a diagnosis of adenomyosis.
These observations provide the first epidemiologic profile of women with a surgical diagnosis of adenomyosis and indicate that this profile differs from that of women with a surgical diagnosis of endometriosis. Our results also suggest that adenomyosis but not endometriosis is associated with increased endogenous exposure to estrogen.
Adenomyosis; endometriosis; epidemiology
Results of several case–control studies suggest that high consumption of meat (all meat, red meat, or processed meat) is associated with an increased risk of renal cell cancer, but only a few prospective studies have examined the associations of intakes of meat, fat, and protein with renal cell cancer.
We conducted a pooled analysis of 13 prospective studies that included 530 469 women and 244 483 men and had follow-up times of up to 7–20 years to examine associations between meat, fat, and protein intakes and the risk of renal cell cancer. All participants had completed a validated food frequency questionnaire at study entry. Using the primary data from each study, we calculated the study-specific relative risks (RRs) for renal cell cancer by using Cox proportional hazards models and then pooled these RRs by using a random-effects model. All statistical tests were two-sided.
A total of 1478 incident cases of renal cell cancer were identified (709 in women and 769 in men). We observed statistically significant positive associations or trends in pooled age-adjusted models for intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, total protein, and animal protein. However, these associations were attenuated and no longer statistically significant after adjusting for body mass index, fruit and vegetable intake, and alcohol intake. For example, the pooled age-adjusted RR of renal cell cancer for the highest vs the lowest quintile of intake for total fat was 1.30 (95% confidence interval [CI] = 1.08 to 1.56; Ptrend = .001) and for total protein was 1.17 (95% CI = 0.99 to 1.38; Ptrend = .02). By comparison, the pooled multivariable RR for the highest vs the lowest quintile of total fat intake was 1.10 (95% CI = 0.92 to 1.32; Ptrend = .31) and of total protein intake was 1.06 (95% CI = 0.89 to 1.26; Ptrend = .37). Intakes of red meat, processed meat, poultry, or seafood were not associated with the risk of renal cell cancer.
Intakes of fat and protein or their subtypes, red meat, processed meat, poultry, and seafood are not associated with risk of renal cell cancer.
To evaluate the reproducibility and validity of the food-frequency questionnaire (FFQ) used in the California Teachers Study (CTS) cohort and to use this data to quantify the effects of correcting nutrient-breast cancer relative risks for measurement error.
195 CTS cohort members participated in a 10-month dietary validation study that included four 24-hour dietary recalls and pre- and post-study FFQs. Shrout-Fleiss intraclass correlations for reproducibility were computed. Under several standard assumptions concerning the correlations of errors in the FFQs and 24-hour recalls, we calculated energy-adjusted deattenuated Pearson correlations for validity and tested for differences in validity according to a number of demographic and other risk factors. For each nutrient, we compared ot performance of the FFQ versus the 24-hour recalls, estimating the number of days of recalls that give equivalent information about true intake as does a single FFQ.. Finally, the effects of adjustment for measurement error on risk estimates were evaluated in 44,423 postmenopausal cohort members, 1,544 of whom developed breast cancer during seven years of follow-up. Relative risks (RR) and confidence intervals (CI) were calculated using Cox proportional hazards with and without correction for measurement error.
Reproducibility correlations for the nutrients ranged from 0.60 to 0.87. With a few exceptions, validity correlations were reasonably high (range: 0.55–0.85), including r=0.74 for alcohol. Performance of the FFQ differed by age for percent of calories from fat and by body mass index and hormone therapy use for alcohol consumption. For most nutrients examined, our FFQ is comparable to two to six recalls for each subject in capturing true intake. In the measurement error-adjusted risk analyses, corrected RRs were within 13% of uncorrected values for all nutrients examined except for linoleic acid. For alcohol consumption the corrected RR (per 20g/1000kcal/d) was 1.36 (95% CI: 1.03–1.51) compared to the uncorrected estimate of 1.25 (95% CI: 1.10–1.42).
The FFQ dietary assessment used in the CTS is reproducible and valid for all nutrients except the unsaturated fatty acids. Correcting relative risk estimates for measurement error resulted in relatively small changes in the associations between the majority of nutrients and the risk of postmenopausal breast cancer.
dietary assessment; reproducibility; validity; calibration; breast cancer; alcohol