Dietary inflammatory index, risk and survival among women with endometrial cancer.

PURPOSE: Chronic inflammation has been implicated in endometrial carcinogenesis yet the impact of potentially modifiable exposures that might affect inflammation, like diet, has been understudied. This study examined the association between the dietary inflammatory index (DII®), a literature-derived tool to assess the inflammatory potential of diet, and risk of developing, and survival after a diagnosis of endometrial cancer (EC). METHODS: This study included data from 1,287 women with EC and 1,435 population controls who participated in the Australian National Endometrial Cancer Study. Energy-adjusted DII (E-DII) scores were calculated from pre-diagnostic dietary intake obtained using a semi-quantitative food frequency questionnaire. Logistic regression was used to assess the association between E-DII scores and risk of EC and proportional-hazards models were used for survival analyses. RESULTS: Higher E-DII scores, reflecting a more pro-inflammatory diet, were not associated with risk of EC [adjusted odds ratio (OR) 0.98, 95% CI 0.77-1.24, p-trend = 0.7]. However, in stratified analyses, higher E-DII scores were associated with increased risk of EC among very obese (BMI 35 + kg/m2) women (OR 1.60, 95% CI 0.80-3.21, p-trend = 0.049, p-interaction = 0.045). After a median follow-up of 7.2 years there were 160 deaths, of which 110 (69%) were from EC. We found no association between E-DII score and survival. CONCLUSION: Greater inflammatory potential of pre-diagnostic diet was not associated with EC risk or survival. Secondary stratified analysis suggested greater inflammatory potential may be associated with EC risk in very obese women.

The association between the inflammatory potential of diet and risk of developing, and survival following, a diagnosis of ovarian cancer.

PURPOSE: Inflammation has been implicated in ovarian carcinogenesis. This study evaluated two dietary indices: the Dietary Inflammatory Index (DII®) and the Empirical Dietary Inflammatory Pattern (EDIP), in relation to risk of developing, and survival following, a diagnosis of ovarian cancer. METHODS: Data came from the Australian Ovarian Cancer Study (1375 cases, 1415 population controls). DII and EDIP scores were computed from dietary information obtained using a semiquantitative food-frequency questionnaire. Logistic regression was used to assess the association between DII and EDIP scores and risk of ovarian cancer and proportional hazards models were used for survival analysis. RESULTS: A high DII score, reflecting a more pro-inflammatory diet, was associated with a modest increased risk of ovarian cancer [odds ratio (OR) DII scoreQ4 vs.Q1 = 1.31, 95% CI 1.06-1.63, ptrend = 0.014]. Likewise a high EDIP score was associated with an increase in risk of ovarian cancer [OR EDIP scoreQ4 vs.Q1 = 1.39, 95% confidence interval (CI) 1.12-1.73, ptrend = 0.002]. We found no association between DII or EDIP score and overall or ovarian cancer-specific survival. CONCLUSION: In conclusion, our results suggest that a pro-inflammatory diet modestly increases the risk of developing ovarian cancer.

Correction to: The association between the inflammatory potential of diet and risk of developing, and survival following, a diagnosis of ovarian cancer.

In the original publication of this article on page 6, paragraph "Discussion", line 4, 'In a U.S. population-based case-control study (n = 493 cases) Peres et al., reported a non-significant association between DII score and risk of developing ovarian cancer of similar magnitude (OR DII scoreQ4 vs. Q1 1.35, 95% CI 0.93-1.97) [20]'. It should read as 'In a U.S. population-based case-control study (n = 493 cases) Peres et al., reported a significant association between DII score and risk of developing ovarian cancer (OR DII scoreQ4 vs. Q1 1.72, 95% CI 1.18-2.51) [20]'.

The association between diabetes, comorbidities, body mass index and all-cause and cause-specific mortality among women with endometrial cancer.

OBJECTIVE: Although endometrial cancer (EC) is associated with relatively good survival rates overall, women diagnosed with high-risk subtypes have poor outcomes. We examined the relationship between lifestyle factors and subsequent all-cause, cancer-specific and non-cancer related survival. METHODS: In a cohort of 1359 Australian women diagnosed with incident EC between 2005 and 2007 pre-diagnostic information was collected by interview at recruitment. Clinical and survival information was abstracted from women's medical records, supplemented by linkage to the Australian National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific survival (EC death vs. non-EC death) associated with each exposure, overall and by risk group (low-grade endometrioid vs. high-grade endometrioid and non-endometrioid). RESULTS: After a median follow-up of 7.1 years, 179 (13%) women had died, with 123 (69%) deaths from EC. As expected, elevated body mass index (BMI), diabetes and the presence of other co-morbidities were associated with a significantly increased risk of all-cause and non-cancer related death. Women with diabetes had higher cancer-specific mortality rates (HR 2.09, 95% CI 1.31-3.35), particularly those who had were not obese (HR 4.13, 95% CI 2.20-7.76). The presence of ≥2 other co-morbidities (excluding diabetes) was also associated with increased risk of cancer-specific mortality (HR 3.09, 95% CI 1.21-7.89). The patterns were generally similar for women with low-grade and high-grade endometrioid/non-endometrioid EC. CONCLUSION: Our findings demonstrate the importance of diabetes, other co-morbidities and obesity as negative predictors of mortality among women with EC but that the risks differ for cancer-specific and non-cancer related mortality.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival.

OBJECTIVE: Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis. METHODS: This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA samples were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 µg 1.30 and 1.43, respectively) and smokers (HRs per 100 µg 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 µg 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98). CONCLUSIONS: Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation.

Impact of weight change and weight cycling on risk of different subtypes of endometrial cancer.

AIM: Obesity is an established risk factor for endometrial cancer. Associations tend to be stronger for the endometrioid subtype. The role of adult weight change and weight cycling is uncertain. Our study aimed to determine whether there is an association between different adult weight trajectories, weight cycling and risk of endometrial cancer overall, and by subtype. METHODS: We analysed data from the Australian National Endometrial Cancer study, a population-based case-control study that collected self-reported information on height, weight at three time points (age 20, maximum and 1 year prior to diagnosis [recent]), intentional weight loss/regain (weight cycling) from 1398 women with endometrial cancer and 1538 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis. RESULTS: Relative to women who maintained a stable weight during adulthood, greater weight gain after the age of 20 was associated with increased risk of endometrial cancer (OR for gain 40+kg all subtypes 5.3, 95% CI 3.9-7.3; endometrioid 6.5, 95% CI 4.7-9.0). The strongest associations were observed among women who were continually overweight from the age of 20 (all subtypes OR 3.6, 95% CI 2.6-5.0). Weight cycling was associated with increased risk, particularly among women who had ever been obese (OR 2.9 95% CI 1.8-4.7), with ~3-fold risks seen for both endometrioid and non-endometrioid tumour subtypes. Women who had intentionally lost weight and maintained that weight loss were not at increased risk. CONCLUSION: These results suggest that higher adult weight gain, and perhaps weight cycling, independently increase the risk of endometrial cancer, however women who lost weight and kept that weight off were not at increased risk.

Intake of omega-3 and omega-6 fatty acids and risk of ovarian cancer.

OBJECTIVES: Limited experimental evidence suggests that omega-3 polyunsaturated (n-3) fatty acids inhibit the proliferation of ovarian cancer cells in vitro, whereas omega-6 polyunsaturated (n-6) fatty acids have been shown to promote carcinogenesis, but epidemiological studies to date have been inconclusive. Our aim was to evaluate the role of polyunsaturated fatty acids in ovarian carcinogenesis. METHODS: Participants in the Australian Ovarian Cancer Study (1,366 cases and 1,414 population controls) self-completed risk factor and food frequency questionnaires. Logistic regression models were used to calculate adjusted odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: We found no association between intake of total n-3 fatty acids from foods, or the individual n-3 fatty acids-alpha-linolenic, eicosapentaenoic, docosapentaenoic, docosahexaenoic acids-and ovarian cancer risk. High intake of total n-6 fatty acids was inversely associated with risk (OR for highest vs. lowest category 0.78, 95 % CI 0.60-1.00, p-trend 0.04); however, the association was restricted to n-6 fatty acids from avocado, vegetables, and nuts. Neither higher intake of the individual n-6 fatty acids nor the ratio of n-3 to n-6 fatty acids was associated with ovarian cancer risk. We found no evidence that risk varied by supplement use. CONCLUSIONS: Our data provide no evidence of a protective role for n-3 fatty acids in ovarian carcinogenesis. The benefit, if any, of higher intake of n-6 fatty acids is due to general properties of the food sources, rather than due to the n-6 fatty acids per se.

Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer.

BACKGROUND/OBJECTIVE: Folates are essential for DNA synthesis and methylation, and thus may have a role in carcinogenesis. Limited evidence suggests folate-containing foods might protect against some cancers and may partially mitigate the increased risk of breast cancer associated with alcohol intake, but there is little information regarding ovarian cancer. Our aim was to evaluate the role of folate and related micronutrients, polymorphisms in key folate-metabolising genes and environmental factors in ovarian carcinogenesis. SUBJECTS/METHODS: Participants in the Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires. DNA samples (1638 cases, 1278 controls) were genotyped for 49 tag single-nucleotide polymorphisms (SNPs) in the methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) genes. Logistic regression models were used to generate adjusted odds ratios and 95% confidence intervals. RESULTS: We saw no overall association between the intake of folate, B vitamins or other methyl donors and ovarian cancer risk, although increasing folate from foods was associated with reduced risk among current smokers (P(trend)=0.03) and folic acid intake was associated with borderline significant increased risks among women who consumed ≥1 standard alcoholic drinks/day (odds ratio (OR)=1.64; 95% confidence interval (CI) 1.05-2.54, P(trend)=0.05). Two SNPs (rs7365052, rs7526063) showed borderline significant inverse associations with ovarian cancer risk; both had very low minor allele frequencies. There was little evidence for interaction between genotype and micronutrient intake or for variation between different histological subtypes of ovarian cancer. CONCLUSIONS: Our data provide little evidence to support a protective role for folate in ovarian carcinogenesis but suggest further evaluation of the joint effects of folic acid and alcohol is warranted.

Carbohydrate intake, glycemic load, glycemic index, and risk of ovarian cancer.

BACKGROUND: Our objective was to determine the relationship between dietary glycemic load (GL), glycemic index (GI), carbohydrate intake, and ovarian cancer risk in a population-based case-control study. PATIENTS AND METHODS: A self-administered questionnaire was used to collect data on demographic and lifestyle factors, and a food frequency questionnaire was used to collect dietary information from 1366 women with ovarian cancer and 1414 population controls. RESULTS: GL was positively associated with ovarian cancer. The adjusted odds ratio (OR) for the highest versus the lowest quartile of intake was 1.24 [95% confidence interval (CI) 1.00-1.55, P for trend = 0.03]. Fiber intake was inversely associated with risk. The OR comparing women in the highest fiber-intake group with those in the lowest was 0.78 (95% CI 0.62-0.98, P for trend = 0.11). We found no association between GI, carbohydrate intake, and ovarian cancer. In analyses stratified by body mass index, the risk estimates for GL, carbohydrate, and sugar were higher among overweight/obese women; however, the interaction term was only significant for sugar (P for interaction = 0.004). CONCLUSIONS: Our results suggest that diets with a high GL may increase the risk of ovarian cancer, particularly among overweight/obese women, and a high intake of fiber may provide modest protection.

Relative weight at ages 10 and 16 years and risk of endometriosis: a case-control analysis.

BACKGROUND: Although previous epidemiological studies have shown that women with endometriosis are more likely to be thinner and underweight, it is currently not clear whether this is a true characteristic of women who develop endometriosis or a consequence of their disease and its symptoms. The aim of this study was to investigate the relationship between endometriosis and relative weight in childhood and adolescence, prior to diagnosis. METHODS: This case-control study included 268 Australian women with surgically confirmed moderate to severe endometriosis (cases) and 244 women without endometriosis (controls). Relative weight at ages 10 and 16 years, as recalled and classified ('underweight', 'average weight' and 'overweight') separately by the women themselves and their mothers, was analyzed. RESULTS: Women who reported being overweight at 10 years had an increased risk of endometriosis (OR 2.8; 95% CI 1.1-7.5). Mothers' reports and concordant responses among mother-daughter pairs were consistent with this association. There was no clear evidence of an association between relative weight at 16 years and risk of endometriosis. CONCLUSIONS: These data suggest that being overweight during late childhood is associated with the development of endometriosis; however, the results warrant confirmation in larger study populations.

The influence of reproductive and hormonal factors on ovarian cancer survival.

Reproductive and hormonal exposures are known to influence ovarian carcinogenesis, but little is known about the effect of these factors on survival. We have studied survival according to hormonal and reproductive history in a population-based cohort of 676 Australian women aged 18-79, newly diagnosed with invasive epithelial ovarian cancer in the early 1990s. In order to place our findings in context, we have also undertaken a systematic review of the pertinent literature. Detailed information about each woman's reproductive and contraceptive history was obtained from pregnancy and contraceptive calendars at the time of diagnosis. Cox regression was used to obtain multivariate adjusted hazard ratios (HR) and 95% confidence intervals (CI). A total of 419 (62%) of the 676 women died during the follow-up (giving a 5-year survival proportion of 44%). Apart from better survival for women who had ever breastfed (multivariate HR 0.74, 95% CI 0.55-0.98), we found no association between survival from invasive ovarian cancer and a range of hormonal and gynecological factors including parity, use of oral contraceptives, and histories of tubal sterilization or hysterectomy. Systematic review of the literature generally supported the lack of influence of these factors on survival from ovarian cancer. We conclude that, except for a possible survival advantage among women with a history of breastfeeding, reproductive and hormonal exposures prior to diagnosis do not influence survival from invasive ovarian cancer, in contrast to their substantial effects on etiology of this disease.