Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery

Objective  Some forms of ovarian neoplasms may be preventable through the removal of precursor lesions. We assessed the risk associated with a prior diagnosis of, and ovarian surgery following, ovarian cysts and endometriosis, with a focus on characterizing risk among tumor subgroups. Methods  Information was collected during in-person interviews with 812 women with ovarian cancer diagnosed in western Washington State from 2002 to 2005 and 1,313 population-based controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results  The risk of a borderline mucinous ovarian tumor associated with a history of an ovarian cyst was increased (OR=1.7, 95% CI: 1.0–2.8), but did not vary notably according to receipt of subsequent ovarian surgery. While risk of invasive epithelial ovarian cancer was slightly increased among women with a cyst who had no subsequent ovarian surgery, it was reduced when a cyst diagnosis was followed by surgery (OR = 0.6, 95% CI: 0.4–0.9). This reduction in risk was most evident for serous invasive tumors. Women with a history of endometriosis had a threefold increased risk of endometrioid and clear cell invasive tumors, with a lesser risk increase among women who underwent subsequent ovarian surgery. Conclusions  Our results suggest differences in the relation of ovarian cysts and endometriosis with risk of specific subtypes of ovarian cancer as well as the possibility that ovarian surgery in women with these conditions may lower the risk of invasive disease. Funding for this work was provided by the National Institutes of Health (RO1 CA87538).     

Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study

New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08-3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26-4.03)] as did those who had smoked less than 15 pack-years of cigarettes [HR = 2.18 (95% CI 1.07-4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.     

Cigarette smoking and risk of epithelial ovarian cancer (Australia)

Objectives: We studied the association between cigarette smoking and ovarian cancer in a population-based case–control study. Methods: A total of 794 women with histologically confirmed epithelial ovarian cancer who were aged 18–79 years and resident in one of three Australian states were interviewed, together with 855 controls aged 18–79 years selected at random from the electoral roll from the same states. Information was obtained about cigarette smoking and other factors including age, parity, oral contraceptive use, and reproductive factors. We estimated the relative risk of ovarian cancer associated with cigarette smoking, accounting for histologic type, using multivariable logistic regression to adjust for confounding factors. Results: Women who had ever smoked cigarettes were more likely to develop ovarian cancer than women who had never smoked (adjusted odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.2–1.9). Risk was greater for ovarian cancers of borderline malignancy (OR = 2.4; 95% CI = 1.4–4.1) than for invasive tumors (OR = 1.7; 95% CI = 1.2–2.4) and the histologic subtype most strongly associated overall was the mucinous subtype among both current smokers (OR = 3.2; 95% CI = 1.8–5.7) and past smokers (OR = 2.3; 95% CI = 1.3–3.9). Conclusions: These data extend recent findings and suggest that cigarette smoking is a risk factor for ovarian cancer, especially mucinous and borderline mucinous types. From a public health viewpoint, this is one of the few reports of a potentially avoidable risk factor for ovarian cancer.     

Active and passive tobacco smoking and the risk of borderline and invasive ovarian cancer (United States)

Objective: A population-based case–control study was conducted to examine the hypothesis that active and passive tobacco smoking were associated with the risk of epithelial ovarian cancer. Methods: In-person interviews were obtained from 558 women with epithelial ovarian cancer (431 invasive, 127 borderline) and 607 population controls regarding active lifetime tobacco smoking, environmental tobacco smoke exposure in utero and during childhood, and other factors that may be related to the development of ovarian cancer. Results: No significant associations of ever or former tobacco smoking with the risk of invasive or borderline ovarian cancer were found, although long-term ex-smokers of 20 years or more were at significantly reduced risk of invasive cancer. Significant, positive dose–response relations of the number of cigarettes smoked per day and pack-years with the odds ratios for borderline cancer were evident. No association of active tobacco smoking with risk was found by histologic subtype of invasive ovarian cancer. Smokers were at significantly increased risk for borderline serous cystadenoma (OR: 1.91; 95% confidence intervals, CI: 1.09–3.34), but not for borderline mucinous cystadenoma. When we limited the analyses to current smokers, age-started smoking was significantly inversely related to the risk of invasive, but not borderline ovarian cancer. We found no association of gestational or childhood environmental tobacco smoke exposure with the risk of invasive or borderline ovarian cancer among never smokers. Conclusions: These findings do not support an association of active tobacco smoking with the risk of invasive ovarian cancer. An increased risk of borderline serous cystadenoma among smokers must be viewed with caution.     

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case‐control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study‐specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow‐up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08–1.28) and former smokers (pHR = 1.10, 95% CI: 1.02–1.18) had worse survival compared with never smoking women. In histotype‐stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01–3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00–1.23; former smoking: pHR = 1.12, 95% CI: 1.04–1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis.     

Association of Reproductive Factors, Oral Contraceptive Use and Selected Lifestyle Factors with the Risk of Ovarian Borderline Tumors: A Danish Case-control Study

Objective The aim was to examine risk factors for ovarian borderline tumors overall, and according to histological subtype (serous vs. mucinous), in a large Danish population-based case-control study. Methods Ovarian borderline cases and controls were recruited from 1995 to 1999, and personal interviews were conducted. In all, 202 cases and 1,564 randomly selected controls were included. The analysis was performed using multiple logistic regression models. Results The risk of ovarian borderline disease decreased with increasing parity (OR=0.79 per birth, 95% CI: 0.63–0.98) and older age at first birth (OR=0.67 per 5 years, 95% CI: 0.53–0.84). Both a history of breastfeeding and use of oral contraceptives reduced the risk of borderline tumor, the effect being most pronounced for serous tumors. Increasing body mass index (BMI) was associated with elevated risk of serous borderline tumor (OR=1.05 per BMI unit; 95% CI: 1.00–1.10), whereas current smoking was a strong risk factor only for mucinous tumors (OR=2.10; 95% CI: 1.22–3.60). Finally, increasing consumption of milk (all types) was found to increase the risk of borderline disease (OR=1.04 per glass milk per week; 95% CI: 1.02–1.06), and increasing intake of total lactose also increased the risk significantly (OR=1.16 per 50 gram lactose per week; 95% CI: 1.06–1.26). Conclusion The risk profile of ovarian borderline tumors is similar to that of ovarian carcinomas, and we observed significant etiological differences between serous and mucinous borderline tumors.     

Association of cigarette smoking with the risk of ovarian cancer

Cigarette smoking may be associated with ovarian cancer risk. This association may differ by histological type. The authors conducted a population-based case-control study in Canada of 442 incident cases of ovarian cancer and 2,135 controls 20-76 years of age during 1994-1997 to examine this association, overall and by histological type. Compared to women who never smoked, those who smoked had higher odds (odds ratio [OR] = 1.22; 95% confidence interval [CI] = 0.98-1.53) of having ovarian cancer, and the OR was larger for ex-smokers (1.30; 95% CI = 1.01-1.67) than for current smokers (1.10; 95% CI = 0.81-1.49). The association with cigarette smoking was stronger for mucinous tumors (OR = 1.77; 95% CI = 1.06-2.96) than for nonmucinous tumors (OR = 1.13; 95% CI = 0.89-1.44). In addition, the odds of smokers having mucinous tumors increased with years of smoking (OR = 1.36, 1.88, 1.19, 4.89 for <20, 21-30, 31-40 and >40 years, respectively; p for trend = 0.002), number of cigarettes smoked per day (OR = 1.55, 1.89, 2.28 for <10, 11-20 and >20 cigarettes/day, respectively; p for trend = 0.014) and smoking pack-years (OR = 1.13, 2.65, 1.77 and 2.39 for <10, 11-20, 21-30 and >30 pack-years, respectively; p for trend = 0.004). Our data suggest that cigarette smoking is associated with an increased risk of ovarian cancer, especially for mucinous types.     

Recreational physical activity and risk of epithelial ovarian cancer

Background

Physical activity may influence ovarian cancer risk through hormonal, inflammatory, or immune-mediated processes or by suppressing ovulation. In a population-based case–control study of epithelial ovarian cancer, we assessed risk associated with recreational physical activity with a focus on characterizing risk within histologic subtypes.

Methods

Information was collected during in-person interviews with 812 women with ovarian cancer diagnosed in western Washington State from 2002–2005 and 1,313 controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Exercise was assessed according to the average hours and metabolic equivalent (MET)-hours per week and the number of years in which regular recreational activity occurred.

Results

Relative to women who reported no regular exercise throughout adulthood, the overall risk of invasive, but not borderline, ovarian cancer was reduced among more active women. Reductions in risk of invasive disease were most evident among women with the greatest frequency of high-intensity activity during adulthood. For serous invasive cancer, women in the uppermost category of MET-hours per week of recreational activity in adulthood had 60% the risk of inactive women (95% CI 0.4–0.9), whereas this level of activity was associated with more than a doubling in risk of endometrioid and clear cell invasive tumors.

Conclusions

Our findings are compatible with an overall reduction in risk of invasive epithelial ovarian cancer associated with recreational activity but suggest that this association may differ in women with different histologic types of disease. Inconsistent findings across studies that have considered histologic type indicate that this issue is not yet resolved.     

Risk of specific types of ovarian cancer after borderline ovarian tumors in Denmark: A nationwide study

Population-based evidence regarding risk of ovarian cancer after a borderline ovarian tumor (BOT) is sparse. We aimed to examine the incidence of specific types of ovarian cancer in women with serous or mucinous BOTs in a nationwide cohort study with up to 36 years of follow-up. Using the nationwide Danish Pathology Data Bank, we identified 4,281 women with a BOT (2,058 serous BOTs and 2,223 mucinous BOTs) in Denmark during 1978–2012. We computed standardized incidence ratios (SIRs) to compare the incidence of ovarian cancer among women with BOTs compared to general population rates. We found that a serous BOT was especially and strongly associated with subsequent serous ovarian cancer (SIR = 9.2; 95% CI: 6.8–12.2), and that a mucinous BOT was strongly related to mucinous ovarian cancer (SIR = 18.6; 95% CI: 10.8–29.8). The SIRs remained elevated ≥10 years after a serous BOT and up to 5–9 years after a mucinous BOT. The increased incidence of serous ovarian cancer in women with a serous BOT was mostly pronounced in women <50 years at the serous BOT diagnosis. In conclusion, women with a serous BOT experience long-term increased incidence of serous ovarian cancer, and women with a mucinous BOT have long-term elevated incidence of mucinous ovarian cancer compared to the general population. This is the first population-based study to show compelling evidence of the histo-specific increased risk of ovarian cancer following specific types of BOTs. Thus, these results are supportive of the hypothesis that BOTs may be precursor lesions to carcinomas of the corresponding histologic type.     

Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study

Few cohort studies have examined the association between cigarette smoking and ovarian cancer risk, either overall, or by histological subtype. In relation to the latter, it has been suggested that mucinous ovarian tumours may be aetiologically unrelated to the other types of epithelial tumours and that their respective associations with cigarette smoking may differ. We examined the association between smoking and ovarian cancer risk using data from participants in a randomised controlled trial of screening for breast cancer involving 89,835 women aged 40-59 years at recruitment. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). During an average of 16.5 years of follow-up, we observed 454 incident cases of ovarian cancer (184 serous, 67 endometrioid, 32 mucinous, 171 other or unknown). We found that women who had smoked for several decades had an approximately two-fold increased risk of epithelial ovarian cancer. Relative to never-smokers, women who had smoked for 40 years or more were at the highest risk (RR=2.50, 95% CI=1.37-4.56). The association with non-mucinous tumours was similar to that observed overall. For mucinous tumours, a two-fold increased risk was observed with smoking of shorter duration, although the number of mucinous tumours in our data-set was small. Long-term cigarette smoking may be associated with an increased risk of epithelial ovarian tumours.     

Cigarette smoking and lung cancer risk according to histologic type in Japanese men and women

Although cigarette smoking is a well‐known risk factor for lung cancer, histology‐specific risk has not been fully clarified in Japan. This case‐control study evaluated the associations between smoking and lung cancer risk according to sex and histologic type. From among patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2009, 1670 lung cancer cases and 5855 controls were selected. History of smoking, quantity and duration of smoking, and passive smoking from spouses were assessed using a self‐administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) for each exposure were estimated by unconditional logistic regression. Ever‐smoking was significantly associated with a higher risk of squamous cell and small cell carcinoma. The OR for these two histologic types combined was larger in women (OR = 24.98, 95% CI: 13.50–46.23) than in men (OR = 9.43, 95% CI: 5.73–15.51). Analysis of the quantity and duration of smoking showed that the OR for each exposure level tended to be larger in women than in men. For adenocarcinoma, clear positive associations with quantity and duration‐related factors were observed among men, and a significant positive association with passive smoking from spouses was found among non‐smoking women (OR = 1.44, 95% CI: 1.06–1.95). These results suggest sex‐ and histologic type‐ differences in the association of smoking with lung cancer risk. Although smoking control should be continued to prevent lung cancers, further studies are required to better clarify differences in smoking‐related lung cancer risk between the sexes and histologic types.     

Long and irregular menstrual cycles,polycystic ovary syndrome,and ovarian cancer risk in a population‐based case‐control study

Long and irregular menstrual cycles, a hallmark of polycystic ovary syndrome (PCOS), have been associated with higher androgen and lower sex hormone binding globulin levels and this altered hormonal environment may increase the risk of specific histologic subtypes of ovarian cancer. We investigated whether menstrual cycle characteristics and self‐reported PCOS were associated with ovarian cancer risk among 2,041 women with epithelial ovarian cancer and 2,100 controls in the New England Case‐Control Study (1992–2008). Menstrual cycle irregularity, menstrual cycle length, and PCOS were collected through in‐person interview. Unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for ovarian cancer risk overall, and polytomous logistic regression to evaluate whether risk differed between histologic subtypes. Overall, we observed no elevation in ovarian cancer risk for women who reported periods that were never regular or for those reporting a menstrual cycle length of >35 days with ORs of 0.87 (95% CI = 0.69–1.10) and 0.83 (95% CI = 0.44–1.54), respectively. We observed no overall association between self‐reported PCOS and ovarian cancer (OR = 0.97; 95% CI = 0.61–1.56). However, we observed significant differences in the association with menstrual cycle irregularity and risk of ovarian cancer subtypes (p_{heterogeneity} = 0.03) as well as by BMI and OC use (p_interaction < 0.01). Most notable, menstrual cycle irregularity was associated with a decreased risk of high grade serous tumors but an increased risk of serous borderline tumors among women who had never used OCs and those who were overweight. Future research in a large collaborative consortium may help clarify these associations.     

Risk factors for ovarian cancer histotypes

To analyse the risk factors for different histologic types of ovarian cancer, we conducted a case-control study. The cases included 750 women with incident, histologically confirmed invasive epithelial ovarian cancer subdivided into: 493 serous, 81 mucinous, 78 endometrioid, and 98 other histologies. The controls included 2411 women admitted to the same hospitals as cases. The odds ratios for women with three or more births, in comparison with nulliparae, were 0.6 for serous, 0.4 for endometrioid, 1.0 for mucinous and 0.7 for other histological types of ovarian cancer. Family history of ovarian/breast cancer was associated to the risk of all ovarian cancer types, except mucinous ones. Selected dietary factors were less strongly directly (meat and starch), or inversely (fish and vitamin E) related to mucinous than to other histological types of ovarian cancer. High occupational physical activity was inversely related to the risk of ovarian cancer, with no heterogeneity across histologies. In conclusion, the association of reproductive factors and of selected dietary habits was weaker for mucinous ovarian cancer than for other histologic types.     

Cigarette smoking and survival after ovarian cancer diagnosis.

We have examined the association between cigarette smoking and ovarian cancer survival in 676 women with invasive epithelial ovarian cancer, recruited into a case-control study in the early 1990s. Information about cigarette smoking and other personal and reproductive factors was obtained from a personal interview at the time of diagnosis. Cox proportional hazards models were used to evaluate the association between cigarette smoking and time to ovarian cancer death. Current smokers at diagnosis were more likely to die early than women who had never smoked [adjusted hazard ratio (HR), 1.36; 95% confidence interval (95% CI), 1.01-1.84]. Increased risks of dying were greater among those who had accumulated more pack-years of smoking (HR for 30+ pack-years compared with never smokers, 1.94; 95% CI, 1.41-2.66) and smoked more cigarettes per day (HR, 1.93; 95% CI, 1.37-2.73). All these associations were stronger among women with late-stage disease (HR for current versus never smokers, 1.58; 95% CI, 1.15-2.18). Time since quitting had little effect on survival after adjusting for lifetime smoking exposure. These results validate and extend recent findings and suggest that premorbid cigarette smoking is related to worse outcome in ovarian cancer patients.     

Cigarette smoking and risk of colorectal cancer among Norwegian women

Objective  The association between cigarette smoking and colorectal cancer (CRC) is still not established. In 2002, Norwegian women had the second highest incidence of CRC in the world. A large proportion of Norwegian women are ever smokers. We examined the association between cigarette smoking and CRC incidence among Norwegian women. Methods  We followed 68,160 women, aged 30–69 years, from the Norwegian Women and Cancer Study who completed a questionnaire in 1996 or 1998 by linkages to national registers through 31 December 2005. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazard models. Subsequently, we estimated the population attributable fraction. Results  Altogether, 425 incident cases of primary, invasive CRC were identified. Ever smokers had a 20% increased risk of CRC (RR = 1.2; 95% CI = 1.0–1.5), a 30% increased risk of colon (RR = 1.3; 95% CI = 1.0–1.7), and a 10% increased risk of rectal (RR = 1.1; 95% CI = 0.7–1.5) cancer compared to never smokers. The population attributable fraction was estimated to be 12% which indicated that approximately one in eight of the CRC cases could have been prevented at a population level. Conclusion  Our results support the hypothesis that cigarette smoking is a preventable cause of CRC among women.     

Risk of nonovarian cancer in a nationwide-based study of nearly 5000 women with borderline ovarian tumors in Denmark

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow-up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR = 1.9; 95% CI: 1.3-2.6), thyroid cancer (SIR = 3.0; 95% CI: 1.4-5.4) and myeloid leukemia (SIR = 3.2; 95% CI: 1.5-5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR = 1.7; 95% CI: 1.3-2.1), pancreatic cancer (SIR = 1.9; 95% CI: 1.2-2.9) and myeloid leukemia (SIR = 2.3; 95% CI: 0.9-4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics.     

吸烟与原发性肝癌关系的巢式病例对照研究

目的 分析吸烟与上海市区中老年男性原发性肝癌的关系.方法 应用巢式病例对照研究方法,对一个18 244名男性队列随访11年,以队列中213例新发肝癌患者作为病例组,按照患者年龄、采样日期、同居住区等配对条件,从队列中随机抽取1094名健康人作为对照组.使用配对Logistic回归分析,调整可能的混杂因素,估计吸烟对肝癌发生的危险度和95%可信区间(CI).结果 调整肝炎、肝硬化、胆石症或其他胆囊病史及乙型肝炎病毒感染等可能的混杂因素后,男性吸烟者患肝痛的危险性是不吸烟者的1.91倍(95%CI为1.28～2.86),日随着每天吸烟量、吸烟年限和吸烟包年数的增加而增加.每天吸烟≥20支者、吸烟≥40年者和吸烟37包年者患肝癌的相对危险度分别为2.16(95%CI为1.37～3.40)、2.14(95%CI为1.18～3.87)和2.12(95%CI为1.21～3.74).吸烟开始年龄越小,危险性越大,吸烟开始年龄<20岁者患肝癌的危险性为2.57(95%CI为1.50～4.40).结论 吸烟是上海市区男性原发性肝癌的危险因素.     

Pooled analysis of the association of <Emphasis Type="Italic">PTGS2</Emphasis> rs5275 polymorphism and NSAID use with invasive ovarian carcinoma risk

Inflammation is postulated to play an important role in ovarian carcinogenesis. Prostaglandin endoperoxide synthase 2 (PTGS2) is responsible for the conversion of arachidonic acid to prostaglandins in response to inflammation. In a pooled analysis of two population-based studies, the Hawaii Ovarian Cancer Case–Control Study and the New England Case–Control Study, including 1,025 women with invasive ovarian carcinoma and 1,687 cancer-free controls, the association of ovarian cancer risk with the PTGS2 rs5275 polymorphism and the use of nonsteroidal antiinflammatory drugs (NSAIDs) were examined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. In the pooled analysis, the CC genotype was associated with a reduced risk of nonserous ovarian carcinoma (OR = 0.66; CI: 0.44–0.98). In addition, the lowest risk was observed among carriers of the CC genotype who were users of only nonaspirin NSAIDs (OR = 0.43; CI:0.20–0.93) in all women combined. The association of PTGS2 rs5275 with nonserous ovarian carcinoma and possible effect modification by NSAID use needs further validation, preferably in prospective studies.     

Serous ovarian, fallopian tube and primary peritoneal cancers: a comparative epidemiological analysis

Invasive serous cancers are diagnosed in the ovary, fallopian tube and peritoneum. It is widely believed that these are variants of the same malignancy but little is known about fallopian tube and primary peritoneal cancers. A comparison of risk factors for these tumor types may shed light on common or distinct aetiological pathways involved in these types of cancer. We investigated risk factors for the three cancers using data from a large Australian population-based case-control study. We included women with incident invasive serous ovarian (n = 627), primary peritoneal (n = 129) and fallopian tube (n = 45) cancer and 1,508 control women. Participants completed a comprehensive reproductive and lifestyle questionnaire. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Hormonal contraceptive use was inversely related to risk of all three cancers. Parity and breast-feeding were also inversely related to risk of serous ovarian and fallopian tube cancer. In contrast, parous women had an increased risk of peritoneal cancer (OR = 1.8, 95%CI 0.8-3.9), and increasing parity did not lower risk. There was also no association between breast-feeding and peritoneal cancer. However, obesity was associated with a doubling of risk for peritoneal cancer alone (OR = 2.1, 95%CI = 1.3-3.4). The strikingly similar patterns of risk for serous ovarian and fallopian tube cancers and the somewhat different results for primary peritoneal cancer suggest that peritoneal cancers may develop along a different pathway. These results also call into question the role of the physical effects of ovulation in the development of serous ovarian cancer.     

A prospective study of fish, marine fatty acids, and bladder cancer risk among men and women (United States)

Objective To evaluate prospectively the association between intakes of fish, marine fatty acids, and bladder cancer risk in two ongoing cohorts, the Health Professionals Follow-up Study and the Nurses’ Health Study. Methods During 16 and 18 years of follow-up, 501 and 235 incident cases of bladder cancer were diagnosed among men and women, respectively. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between fish intake and bladder cancer risk adjusting for age, total caloric intake, pack-years of cigarette smoking, and current smoking. Results We observed no significant overall association between total fish intake and bladder cancer risk, even when we compared ≥1 servings of fish per day to fish intake ≤1–3 servings per month. Among men, a statistically significant lower risk of bladder cancer was observed among men consuming fish or high marine fatty acid, after excluding the first 4 years of follow-up (MV RR = 0.60; 95% CI, 0.38–0.94, for ≥1 total fish servings per day compared to ≤1–3 servings per month). Conclusions Overall, these findings suggest that fish intake is not likely to be appreciably associated with the risk of bladder cancer.