Our study is the first to look at APC in a large cohort of veterans surviving CRC. To significantly reduce any genetic bias, we excluded all veterans with CRC related to any genetic syndromes such as Lynch or familial adenomatous polyposis, or inflammatory diseases such as Crohn’s or ulcerative colitis. We showed that veterans surviving CRC had a very high incident of APC, that veterans with APC differed from those without APC in age and period of war service. We showed distinct difference in age and specific APC distribution between veterans surviving RCC versus LCRC.
Sex distribution in the veteran population has always been male dominant. The national distribution of female veterans 40 or older ranges from 2.4 to 16.4% (13). Our cohort distribution of 1% female skewed heavily toward prostate cancer as one of the major APCs. Our low representation of PGW veterans (1.3%) likely reflected the fact that many of the PGW veterans were not old enough to be at risk for CRC during our study period (1995–2011). Stage distribution of CRC in our cohort was similar to the distribution of 40% localized (I and II), 36% regional (III), and 20% distance (IV) reported in the general population during the period of 2001–2010 (1). Our distribution of 36.8% RCC and 56.4% LCRC was also similar to the distribution of 38% proximal colon and 55% distal colon and rectum seen in male CRC patients in the general population during the same time period. These findings indicated that manifestation of CRC in our veteran cohort is similar to manifestation of CRC seen in the general population.
We found a very high incidence of APCs in veterans surviving CRC with more than one out of four veterans had at least one APC. The rate of APC was statistically different if we grouped our cohort according to the war service, with the highest rate seen in Korean War veterans and the lowest seen in Vietnam War veterans. This difference in APC rate could not be entirely attributed to age since the oldest group was WWII veterans with the second highest rate of APCs. Our finding suggested that each group of veterans could be exposed to hazardous factors unique to their period of war service. It has been showed that CRC survivors in the general population are at higher risks of developing APCs. This risk varies among various reports ranging from 4.9–11.5% (2–4). Yet, the highest rate of APC in CRC survivor in the general population remains significantly lower than the lowest rate 18.1% seen in Vietnam War veterans. Our findings suggest that veterans face additional occupational hazard that strongly increases their risks of APCs. This occupational hazard is likely war specific and currently not identified or understood.
For men in the general population, the average age at diagnosis of colon and rectal cancer is 68 and 63 respectively (23). The average age of our cohort, the RCC and LCRC subgroup were older (70, 71.8 and 68.7 respectively). This is in keeping with the finding that male veterans are older than their civilian counterparts (12). We found that the oldest subgroup in our cohort were WWII veterans followed by Korean War veterans, Vietnam War veterans, and PGW veterans, consistent with the timeline of these war periods.
We looked at the distribution of APC in our cohort. The ten most common APCs in our cohort are cancer of the prostate (38.4%), lungs (15.3%), bladder (11.8%), blood (8.4%), kidney (6.4%), colon and rectum (6.2%), oral cavity and pharynx (6%), esophagus (2.9%), melanoma (2.7%), and pancreas (1.8%). Both the RCC and the LCRC subgroup had a similar distribution. As a whole and within subgroup, cancer of the prostate, lungs and bladder make up more than two third of all APCs. As comparison, the ten most common APCs in CRC survivors in the United States are cancer of the prostate (20.1%), lungs (18.7%), breast (11.3%), bladder (6.9%), non-Hodgkin lymphoma (4.5%), melanoma (3.5%), kidney (3.3%), endometrium (3.1%), and thyroid (1.4%) (2). Prostate, lungs and bladder cancer remain prominent survivors of CRC in the general population. There is no statistical difference in the trend seen in our cohort as compared to the trend seen in the general population. These findings indicate that the general characteristic of veterans surviving CRC in our cohort is similar to the characteristic seen in CRC survivors in the general population.
There has been ample evidence showing distinct difference between RCC and LCRC in the general population (16–22). We sought to determine if these differences existed in our cohort. In the general population, patients with right colon cancer were older than patients with left colon cancer or rectal cancer (57 vs 53 or 54, respectively) (25). Similarly, we found that our RCC cohort were older than our LCRC cohort (71.7 vs 68.8, p < 0.001). Interestingly, we found that when stratifying by sidedness, our CRC surviving veterans remained consistently older than their civilian cohort (71.7 vs 57 and 68.8 vs 53 or 54, for RCC and LCRC cohort respectively). We also found a significantly higher incidence of APCs in RCC cohort (32.9% vs 22.9%, p < 0.0001). This difference persisted in age-matched RCC and LCRC cohort (32.9% vs 25.5%, p = 0.00678), indicating that older age in the RCC cohort is not responsible for the higher rate of APCs. So far, this finding has not been reported in the literature. Recently, it has been reported that sporadic RCC behaves similarly to RCC associated with Lynch syndrome (26). When we compared the overall incidence of Lynch syndrome-related APCs including additional CRC, cancer of the kidney, bladder, liver, pancreas, small bowel and stomach, we found that veterans with RCC had a higher rate of Lynch syndrome-related APCs as compared to their LCRC cohort.
Our study has several limitations. First, it is a retrospective review of a veteran population in a geographically specific area and may not represent all veterans. Second, several cofounders including alcohol, smoking, obesity, known hazard exposure including Agent Orange and Camp Lejeune exposure were not collected. These confounders are known to increase the risks of developing malignancy. Third, we did not record the temporal sequences of the CRC and the APCs and thus we could not directly link the risks of APC to the index CRC.