Age of Diagnosis Influences Risk Factors in Pancreatic Cancer

In an interview with Targeted Oncology, Chen Yuan, MD, further discussed the research on the age-dependent associations and risks for patients with pancreatic cancer.

Risk factors deemed to be inherited or lifestyle-associated risk factors strongly correlate with earlier-onset pancreatic cancer and show the importance of age at initiation to prevent cancer and control programs targeting this malignancy.

While more than 80% of patients with pancreatic cancer have it present as advanced disease, experts are unaware of the appropriate ages to consider for prevention and early detection strategies.

A study led by Chen Yuan, MD, observed a total of 167,483 participants from 2 prospective cohort studies in the United States with 1190 incident cases of pancreatic cancer during more than 30 years of follow-up were included in the trial. There were 5,107 cases of pancreatic cancer, 8,845 participants in the control arm of a completed multicenter genome-wide association study, and 248,893 pancreatic cancer cases which were documented in the United States Surveillance, Epidemiology, and End Results Program.

Investigators looked at multiple lifestyle factors they thought may influence earlier-onset pancreatic cancer, including cigarette smoking, obesity, diabetes, height, and non-O blood group. The main goal of the study was to evaluate the risk of developing pancreatic cancer by age.

Findings revealed that all 5 risk factors were more strongly associated with pancreatic cancer risk among younger participants, with reduced associations in patients those 70 years and older. Among participants aged 60 years and younger, the hazard ratios for participants with 3-5 risk factors vs no risk factors were 9.24 (95% CI, 4.11-20.77), 3.00 (95% CI, 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI, 1.10-1.94) among those aged 70 years and older.

“We were able to demonstrate what we hypothesized. We found an age dependent pattern for nearly all these risk factors for pancreatic cancer, whereby inherited and lifestyle factors play a greater role in development of early onset versus late onset pancreatic cancer,” said Yuan, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, in an interview with Targeted OncologyTM.

According to Yuan, these factors were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. This study showed the age-dependent pattern of risks for nearly all established risk factors for pancreatic cancer.

Due to findings revealing the associations between risk factors and pancreatic cancer to be strongest among younger participants and weakened with age, the age of target populations should be considered when designing prevention and control programs for pancreatic cancer.

In the interview, Yuan further discussed the research on the age-dependent associations and risks for patients with pancreatic cancer.

Targeted Oncology: Can you discuss the purpose of this research on age-specific associations and attributes on the risks of pancreatic cancer?

Yuan: The purpose of this study was to test the hypothesis that early-onset pancreatic cancer could be most strongly associated with inherited and lifestyle factors than later onset pancreatic cancer. As you may know, pancreatic cancer is the third major cause of cancer related deaths in the United States. Age is known to be the strongest risk factor for pancreatic cancer. The incidence and death rates of pancreatic cancer substantially increase with age in the United States.

In the past several decades, the US pancreatic cancer incidence has widened at all ages, particularly among young populations. Later onset cancers may have fewer driver events caused by inherited and lifestyle factors and more from random mutations. Previous studies also found that pancreatic cancer cases with certain risk factors have a younger age of onset, compared with those without the factors.

Can you discuss what was investigated in the study?

In this study, we look at different risk factors in different patient populations. We utilized full notch population-based studies, including 2 prospective cohort studies. A previously completed multicenter genome-wide association study as well as the U.S. Surveillance, Epidemiology, and End Results Program. We were looking at multiple established risk factors for pancreatic cancer, including inherited and lifestyle factors.

Which specific factors were examined within the trial?

Specifically, we looked at lifestyle factors, including cigarette smoking and obesity, inherited factors including non-O blood group and height. Non-O blood group and a tall height is thought to be associated with higher risk of pancreatic cancer. We also looked at a genetic risk score composed of 22 single nucleotide polymorphisms that have been identified by previous genome wide association studies.

In addition, we look at demographic factors, including sex and race, because males and Black people are at higher risk for pancreatic cancer compared with females and White people, respectively. All these factors have been convincingly associated with pancreatic cancer risk in previous studies.

What were the key findings of this research?

We were able to demonstrate what we hypothesized. We found an age-dependent pattern for nearly all these risk factors for pancreatic cancer, whereby inherited and lifestyle factors play a greater role in development of early onset vs late onset pancreatic cancer. For example, compared with never smokers, those who had ever smoked had a nearly 2-fold increased risk among those aged 60 years or younger.

While the association was naturally attenuated among those over 70 years, we noted a similar trend for obesity and other risk factors. When we consider these risk factors in combination, they are related to more than 60% of pancreatic cancers, aged 60 years or younger, in contrast to less than 20% over 70 years.

What did your research reveal regarding behavioral changes to reduce cancer risk?

Because cigarette smoking and obesity were not strongly associated with pancreatic cancer risk after age 70, preventive interventions related to these factors will require implementation at the younger ages to maximize the effectiveness.

In this study, we also find that smoking cessation at earlier ages is associated with more pronounced risk reduction for pancreatic cancer. Specifically, individuals who were smoking before age 50, had almost the same risk reduction as individuals who never smoked. Similarly, obesity onset before age 50 years, rather than at later ages, was associated with increased risk of pancreatic cancer. If people want to prevent pancreatic cancer, they should do lifestyle interventions at younger ages.

How do you think these findings will influence the future of this space?

Risk factor identification and prediction models for pancreatic cancer in the future will need to consider age, not only as a risk marker of pancreatic cancer, but also as a stratification variable that could modify the association or predictive ability of these risk factors.

Second, regarding early detection strategies of pancreatic cancer, the strategies considering tumor induced symptoms or signs may be more useful than those solely based on risk factors themselves. These are the major implications of this research for the future.

How would you advise your peers in primary care to help patients reduce their cancer risk?

While 50% of pancreatic cancers are diagnosed at age 70, younger cases contribute greatly to the society burden of this disease. Because this is a very deadly disease, and the younger cases could cause substantial amounts of potential life years.

To prevent early onset pancreatic cancer, lifestyle interventions would require implementation at younger ages. Conversely, early detection programs may have greater potential to reduce pancreatic cancer mortality in all populations.

Reference:
Yuan C, Kim J, Wang QL, et al. The age-dependent association of risk factors with pancreatic cancer. Ann Oncol. 2022;33(7):693-701. doi:10.1016/j.annonc.2022.03.276