Incidence of cancer among grand multiparous women in Finland with special focus on non-gynaecological cancers : A population-based cohort study

Background. Many studies have previously revealed evidence of an association between grand multiparity (five or more deliveries) and gynaecological cancer. Oestrogen has an impact on cancer formation and the amount of circulating oestrogen is significantly higher during pregnancy. Also the lifestyle of grand multiparous women differs somewhat from the average population. Considering these factors it is plausible that also non-gynaecological cancers are associated with multiparity. The aim of our study was to determine cancer incidence among grand multiparous women, with special attention to non-gynaecological cancers. Material and methods. All 102 541 women alive in 1974-2011 and having had at least five deliveries were identified in the Finnish Population Register and followed up for cancer incidence through the Finnish Cancer Registry to the end of 2011. Standardised incidence ratios (SIRs) were defined as ratios between observed and expected numbers of cases, the latter ones based on incidence in the entire Finnish female population. Results. The overall incidence of non-gynaecological cancers was the same as in the reference population (SIR 0.98, 95% confidence interval 0.90-1.06). The incidence of cancers of the gall-bladder (SIR 1.42, 1.26-1.58), biliary tract (1.19, 1.04-1.35) and kidney (1.22, 1.14-1.31) was increased. There were significantly fewer cases than expected of urinary bladder cancer (SIR 0.70, 0.61-0.78), lung cancer (0.87, 0.81-0.92), colon cancer (0.94, 0.89-0.99) and all types of skin cancers. As a consequence of the decreased incidence of gynaecological cancers (SIR 0.74, 0.71-0.77) and breast cancer (0.60, 0.58-0.61), the SIR for cancer overall was 0.84 (0.83-0.85). Conclusion. The study demonstrated that grand multiparous women have a similar overall risk of non-gynaecological cancers as other women, despite significant differences in some specific forms of cancer.Peer reviewe

Prognosis of ovarian cancer in women with type 2 diabetes using metformin and other forms of antidiabetic medication or statins : a retrospective cohort study

Abstract Background Ovarian cancer is one of the most lethal cancers and women with type 2 diabetes (T2D) have even poorer survival from it. We assessed the prognosis of ovarian cancer in women with type 2 diabetes treated with metformin, other forms of antidiabetic medication, or statins. Methods Study cohort consisted of women with T2D diagnosed with ovarian cancer in Finland 1998–2011. They were identified from a nationwide diabetes database (FinDM), being linked to several national registers. Patients were grouped according to their medication in the three years preceding ovarian cancer diagnosis. The Aalen–Johansen estimator was used to describe cumulative mortality from ovarian cancer and from other causes in different medication groups. Mortality rates were analysed by Cox models, and adjusted hazard ratios (HR) with 95% confidence intervals (95% CIs) were estimated in relation to the use of different forms of medication. Main outcome measures were death from ovarian cancer and death from other causes. Results During the accrual period 421 newly diagnosed ovarian cancers were identified in the FinDM database. No evidence was found for any differences in mortality from ovarian cancer or other causes between different antidiabetic medication groups. Pre-diagnostic use of statins was observed to be associated with decreased mortality from ovarian cancer compared with no such use (HR 0.72, 95% CI 0.56–0.93). Conclusions Our findings are inconclusive as regards the association between metformin and ovarian cancer survival. However, some evidence was found for improved prognosis of ovarian cancer with pre-diagnostic statin use, requiring cautious interpretation, though

Incidence of gynaecological cancers and overall and cause specific mortality of grand multiparous women in Finland

Abstract The aim of this population-based cohort study was to evaluate the incidence and relative risk ratios of gynaecological cancers and the mortality of women with at least five children (GM women) compared to the average of Finnish women. We linked together the data of the Population Register (1974–1997), the Finnish Cancer Registry and the national cause-of death files of Statistics Finland (1974–2001) by using a personal identification code. The study population consisted of 86 978 GM women (1974–1997), including 3 752 women with at least 10 children (GGM women). Altogether 7 604 cancer diagnoses and 18 870 deaths were recorded. The incidence (SIR) of breast (0.55, 95% CI 0.52–0.58), endometrial (0.57, 95% CI 0.52–0.63) and ovarian cancer (0.64, 95% CI 0.55–0.73) decreased, and that of cervical cancer (1.13, 95% CI 0.98–1.29) increased in GM women. In multivariate analysis, the increase in parity from five to eight increased the protection against breast and endometrial cancer, but not in ovarian or cervical cancer. A young age at first birth decreased the breast cancer risk, while an older age at first birth decreased the risk for endometrial and cervical cancer. A short premenopausal delivery-free period and a long birth period were risk reducers in women who contracted endometrial cancer after menopause. The mortality (SMR) of breast (0.64, 95% CI 0.59–0.69), endometrial (0.68, 95% CI 0.56–0.80), ovarian cancer (0.68, 95% CI 0.60–0.75) as well as for dementia (0.80, 95% CI 0.72–0.84) decreased. The SMR of kidney (1.38, 95% CI 1.21–1.56) cancer increased in the GM group. The SMR of ischemic heart diseases (1.10, 95% CI 1.08–1.13) and diabetes mellitus (1.42, 95% CI 1.29–1.55) increased. The overall SMR of GM women was 5% less than expected (95% CI 0.94–0.95; deficit 949 deaths), but among GGM women it coincided with the national average (1.01, 95% CI 0.93–1.08). Multiparity affected the spectrum of diseases and causes of death in a specific way: the pregnancy-specific hormonal milieu is responsible for the low SIR and SMR of hormone-dependent cancers, and increased body weight is lightly responsible for the high SMR of cardiovascular and metabolic diseases. These observations advocate for delivering the first child at an age younger than 30 years and to start measures for careful weight control not only during and after pregnancies but even later and permanently

Antidiabetic medication, statins and the risk of endometrioid endometrial cancer in patients with type 2 diabetes

Abstract Objective: To gain further evidence of an association between the incidence of endometrial cancer (EC) and the use of metformin, other antidiabetic medication (ADM) and statins in women with type 2 diabetes (T2D). Methods: A retrospective cohort of 92,366 women with newly diagnosed T2D was obtained from a diabetes register (FinDM). 590 endometrioid ECs were observed during the follow-up time. Poisson regression was utilized to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of the endometrioid EC in relation to the use of metformin, other oral ADM, insulin and statins. Nested case-control analyses were performed, where up to 20 controls were matched for age and duration of DM for each EC case. The HRs were estimated by conditional logistic regression for never/ever and cumulative use of different forms of ADM and statins. Results: In the case-control analyses the use of metformin (HR 1.24, 95% CI 1.02–1.51) and other oral ADM (HR 1.25, 95% CI 1.04–1.50) was associated with an increased incidence of endometrioid EC compared to no ADM use. No difference was observed between metformin users and those using other oral ADMs. The use of statins was inversely related to the incidence of endometrioid EC (HR 0.78, 95% CI 0.65–0.94). Results from the full cohort analysis supported this finding. Conclusions: In our study the use of metformin or other oral forms of ADM was not associated with a lowered risk of endometrioid EC in women with T2D. Instead statins were observed to be inversely associated with endometrioid EC in this population

Antidiabetic medication, statins and the risk and prognosis of non-endometrioid endometrial cancer in women with type 2 diabetes

Abstract Aim: To determine the incidence and prognosis of non-endometrioid endometrial cancer (EC) in relation to the use of metformin, other antidiabetic medication (ADM) and statins in patients with type 2 diabetes (T2D). Materials and Methods: In order to analyze the incidence and prognosis of non-endometrioid EC, two cohorts were obtained from a nationwide diabetes database (FinDM); 57 non-endometrioid ECs were observed in a cohort of 92,366 women with newly-diagnosed T2D during the follow-up (1996 to 2011) to assess the incidence, and a retrospective cohort of 105 women with T2D diagnosed with non-endometrioid EC (1998 to 2011) was used to estimate cumulative mortality from EC and other causes of death. Hazard ratios (HRs) with 95% confidence intervals (CIs) for EC incidence were estimated in the full-cohort analysis and in the nested case–control analysis, matched for age and duration of T2D. Cumulative mortality was estimated by using the Aalen–Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models regarding the pre-diagnostic use of different forms of ADM and statins. Results: In the nested case–control analysis, the use of metformin was not associated with the risk of non-endometrioid EC (HR=1.09, 95% CI=0.59–2.00), whereas statin use was associated with a lower risk (HR=0.47, 95% CI=0.26–0.84). The results from the full-cohort analysis supported these findings. Mortality from non-endometrioid EC was not different between users of metformin and other types of oral ADM (HR=1.56, 95% CI=0.40–6.07) but was observed to be lower in statin users (HR=0.41, 95% CI=0.20–0.82). Conclusions: Our findings were inconclusive regarding the association of metformin with the risk and prognosis of non-endometrioid EC. However, statin use was associated with a lower incidence and mortality from this disease

The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes:a cohort and nested case–control study

Abstract Objective: To obtain evidence of the effects of metformin and statins on the incidence of ovarian cancer in women with type 2 diabetes (T2D). Design: A retrospective cohort study and nested case–control study. Setting: The data were obtained from a diabetes database (FinDM) combining information from several nationwide registers. Population: A cohort of 137 643 women over 40 years old and diagnosed with T2D during 1996–2011 in Finland. Methods: In full cohort analysis Poisson regression was used to estimate the hazard ratios (HR) in relation to ever use of metformin, insulin other oral anti‐diabetic medication or statins. In the nested case–control analysis 20 controls were matched to each case of ovarian cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different medications. The estimates were adjusted for age and duration of T2D. Main outcome measure: Incidence of ovarian cancer. Results: In all, 303 women were diagnosed with ovarian cancer during the follow up. Compared with other forms of oral anti‐diabetic medication, metformin (HR 1.02, 95% CI: 0.72–1.45) was not found to be associated with the incidence of ovarian cancer. Neither was there evidence for statins to affect the incidence (HR 0.99, 95% CI: 0.78–1.25). In nested case–control analysis the results were essentially similar. Conclusions: No evidence of an association between the use of metformin or statins and the incidence of ovarian cancer in women with T2D was found. Tweetable abstract: No evidence found for metformin or statins reducing the incidence of ovarian cancer