Association between oral contraceptive use and pancreatic cancer risk

Article by Master, Doctor Mai Vien Phuong - Gastrointestinal endoscopist - Department of Medical Examination & Internal Medicine - Vinmec Central Park International General Hospital.

Regarding the association between pancreatic cancer risk and oral contraceptive (OC) use, epidemiological studies have shown conflicting results. Some findings show a positive association with pancreatic cancer risk, while some studies indicate an opposite association.

Pancreatic cancer is the 7th most common cause of death among malignancies in women, with approximately 220000 deaths worldwide in 2018. Pancreatic cancer is one of its kind. most deadly cancers, with an estimated five-year survival rate of less than 10%. Pancreatic cancer mortality is characterized by a significant increase after age 30, reaching the peak burden in women around the age of 80. Understanding the causes of pancreatic cancer has improved significantly. over the past decades and certain risk factors have been established, including tobacco use; fat; diabetes ; chronic pancreatitis ; positive family history and genetic syndromes; drink a lot of alcohol; dietary factors; physically inactive; workplace exposure to certain chemicals, infection. Although several risk factors have been identified, the causes of pancreatic cancer are not fully known.

Regarding the association between pancreatic cancer risk and oral contraceptive (OC) use, epidemiological studies have shown mixed results. Some findings show a positive association with pancreatic cancer risk, while some studies indicate an opposite association. A previous meta-analysis of observational studies did not support the hypothesis that oral contraceptive use is associated with pancreatic cancer risk (pooled relative risk [RR] = 1.09). , 95% confidence interval [CI] 0.96–1.23). In a large systematic study and meta-analysis from multiple centers, the authors identified 10 case-control studies and 11 cohort studies investigating the association between oral contraceptive use and cancer. pancreatic letter. The authors' meta-analysis of these 21 studies, including 7700 cases of pancreatic cancer, showed that OC use was statistically significantly associated with a reduced risk of pancreatic cancer. However, the association was not significant when duration of oral contraceptive use of less than 1 year, less than 5 years, 5-10 years and longer than 10 years was evaluated for pancreatic cancer risk. A significantly reduced risk of pancreatic cancer in women using oral contraceptives has been documented in higher quality studies, studies conducted in Europe and in postmenopausal women. Differences in the incidence of pancreatic cancer between the sexes, specifically the higher prevalence of pancreatic cancer in men than in women, has led to investigations into the possible reasons behind these this difference. In addition to the influence of environmental factors, it has been hypothesized that female sex hormones may be responsible for the reduced incidence of pancreatic cancer in women. In vitro and in vivo studies have shown that the pancreas contains estrogen, androgen, estrogen suppressor and testosterone receptors that promote the occurrence of some pancreatic cancers.

Many observational studies have investigated the role of oral contraceptive use and pancreatic cancer risk, but results have been inconsistent. While some authors have reported an inverse relationship between oral contraceptive use and pancreatic cancer risk, other studies have not confirmed these findings. However, no published studies have found a significant positive relationship between OC use and pancreatic cancer. With regard to duration of OC use, the authors' meta-analyses did not identify a significant association with pancreatic cancer risk.
However, one cohort study showed a significant increase in pancreatic cancer risk in women using OCs <1 year (HR = 1.65, 95% CI: 1.08-2.50). , but the number of cases of pancreatic cancer in the group of women who had taken OCs for less than 1 year was small. In addition, a hospital-based case-control study (NOS score assessed as 6) found a limited positive association with duration of OC use of 5-10 years, > 10 years, and risk Pancreatic Cancer. Despite the small number of cases in these groups, the P for propensity is significant (<0.01). In contrast, Kreiger et al found a significantly reduced risk of pancreatic cancer in women who used OCs for longer than 6 months. Differences in results between studies may be explained by differences in study design, study populations, exposure assessments, definitions of exposure, and limitations. different for OC usage time.
In addition, most studies reported adjusted risk estimates for known and potential pancreatic cancer risk factors (age, diabetes, smoking, obesity), but with fewer studies also provides adjusted estimates for history of pancreatitis, family history of pancreatic cancer and high alcohol consumption, and age.

While several included studies have adjusted for factors related to diet, this body mass index (BMI) is most commonly involved, with only two investigating nutritional variables such as: Green tea intake, dietary vitamin C intake, coffee, tofu consumption and dietary fat intake. Obesity is a risk factor for pancreatic cancer. However, the mechanisms are not fully known and may involve sex hormones. A high BMI may reflect high dietary fat intake, although findings regarding its association with pancreatic cancer risk have been inconsistent. Notably, adipose tissue produces estrogen and may have a protective role. Therefore, dietary factors may confound the association between pancreatic cancer risk and oral contraceptive use. Similarly, studies investigating nutrition and pancreatic cancer risk should adjust for reproductive factors such as oral contraceptive use.

A search of the authors' literature revealed a previously published meta-analysis assessing the association of pancreatic cancer risk with female hormonal factors and menstruation, a meta-analysis from the International Association of Pancreatic Cancer Case Controls. Contrary to the authors' results, a previous meta-analysis found no significant association between pancreatic cancer risk and the composite RR using OCs from 6 case-control studies and 8 studies. cohort was 1.09 (95% CI: 0.96-1.23). The authors then note that their subgroup analyzes by study design showed a slightly increased risk of pancreatic cancer that was associated with OC use in the cohort studies (RR = 1.09, 95% CI: 1.00-1.29). Authors' subgroup analyzes by study design determined the opposite, namely a borderline insignificant outcome for the inverse association (RR = 0.84, 95% CI: 0.70-1.00).
However, the authors identified publication bias for studies on OC exposure, which may mask the actual association. The authors' meta-analysis included 4 additional case-control studies and 3 cohort studies, totaling 7700 cases of pancreatic cancer compared with 5084 in the previous meta-analysis, specifically the analysis of the authors. The author failed to identify publication bias. In addition, the authors' study had no linguistic limitations in the literature search in contrast to previously performed meta-analyses.
In summary, the association between pancreatic cancer risk and oral contraceptive (OC) use showed mixed results. Some findings show a positive association with pancreatic cancer risk, while some studies indicate an opposite association.

References:
Ilic M, Milicic B, Ilic I. Association between oral contraceptive use and pancreatic cancer risk: A systematic review and meta-analysis . World J Gastroenterol 2021; 27(20): 2643-2656 [DOI: 10.3748/wjg.v27.i20.2643]