Citation Nr: 21031906 Decision Date: 05/24/21 Archive Date: 05/24/21 DOCKET NO. 16-34 881 DATE: May 24, 2021 ORDER New and material evidence having been received, the petition to reopen the previously denied claim of service connection for colon cancer for accrued and substitution purposes is granted. Entitlement to service connection for colon cancer, to include as due to exposure to herbicides is granted. Entitlement to service connection for the cause of the Veteran's death, to include as due to exposure to herbicides is granted. FINDINGS OF FACT 1. In a December 2010 rating decision, the RO denied service connection for colon cancer; notice of that decision was provided to the Veteran that same month. The Veteran did not appeal the December 2010 rating decision or submit new and material evidence during the appeal period of that decision. 2. Evidence received since the December 2010 rating decision is new and relates to an unestablished fact necessary to substantiate the claim for service connection for colon cancer. 3. The Veteran was first diagnosed with colon cancer in 2010; his death certificate reflects that he died in February 2010, with colon cancer listed as the underlying cause of death. 4. Resolving reasonable doubt in favor of the appellant, competent medical evidence indicates the Veteran's colon cancer, which was later the underlying cause of his death, is related to service, to include exposure to herbicides therein. CONCLUSIONS OF LAW 1. The December 2010 rating decision is final with respect to the Veteran's claim to establish service connection for colon cancer; new and material evidence has been received to reopen the claim for service connection for colon cancer. 38 U.S.C. §§ 5108, 7105; 38 C.F.R. § 3.156. 2. The criteria for establishing service connection for colon cancer have been met. 38 U.S.C. §§ 1110, 1112, 1116, 5107; 38 C.F.R. §§ 3.102, 3.303, 3.307, 3.309. 3. The criteria for establishing service connection for the cause of the Veteran's death have been met. 38 U.S.C. §§ 1110, 1310, 5107; 38 C.F.R. §§ 3.102, 3.303, 3.307, 3.309, 3.312. REASONS AND BASES FOR FINDINGS AND CONCLUSIONS The Veteran had active military service from May 1966 to May 1969. He died in February 2015 and the appellant is his surviving spouse. These matters come before the Board of Veterans' Appeals (Board) on appeal from a June 2015 rating decision of the Department of Veterans Affairs (VA) Regional Office (RO). The Board denied the Veteran's claim in a May 9, 2018, decision, and the Veteran appealed the decision to the United States Court of Appeals for Veterans Claims (Court). The parties filed a Joint Motion for Remand (Joint Motion), and a September 2019 Order of the Court vacated the Board's decision that denied the Veteran's claim for service connection for cause of death because it did not provide adequate reasons or bases for its decision. More specifically, the Board failed to consider entitlement to Dependency and Indemnity Compensation (DIC) under a 38 U.S.C. § 1318(b). The appellant's claim for an earlier effective date for entitlement to increased compensation based on unemployability (TDIU) is also still on appeal and a grant may entitle him to DIC based upon being in receipt of a total disability rating for 10 years prior to his death. Furthermore, the Joint Motion concluded that the Board did not consider whether the Veteran's statements constituted an informal request to reopen his claim for service connection for colon cancer and that the claim was therefore pending at the time of his death. These matters were previously remanded by the Board in June 2020. 1. Whether new and material evidence has been received to reopen a claim for service connection for colon cancer, to include as due to exposure to herbicides for accrued and substitution purposes is granted. Generally, if a claim of entitlement to service connection has been previously denied and that decision became final, the claim can be reopened and reconsidered only if new and material evidence is presented with respect to that claim. 38 U.S.C. § 5108. New evidence means existing evidence not previously submitted to VA. Material evidence means existing evidence that, by itself or when considered with previous evidence of record, relates to an unestablished fact necessary to substantiate the claim. 38 C.F.R. § 3.156(a). New and material evidence can be neither cumulative nor redundant of the evidence of record at the time of the last prior final denial of the claim sought to be reopened and must raise a reasonable possibility of substantiating the claim. Id. In a December 2010 rating decision, the RO denied service connection for colon cancer, to include as due to exposure to herbicides based upon a finding that the Veteran's colon cancer was not caused or aggravated by service, nor was colon cancer on the list of conditions that VA has determined are presumptively due to exposure to herbicides, nor had colon cancer manifested within one year post-service such that service connection could be granted on a presumptive basis. The Veteran was provided notice of the decision and his appellate rights but did not appeal the decision or submit new and material evidence within one year of the decision. Therefore, the decision is final. See 38 C.F.R. §§ 3.156, 20.302, 20.1103. The evidence received since the December 2010 rating decision includes evidence that is both new and material to the claim. See 38 C.F.R. § 3.156. Specifically, in April 2020, the Veteran submitted a private medical opinion between exposure to herbicides and the development of colon cancer. Accordingly, the claim is reopened and must be considered on the merits. See Justus v. Principi, 3 Vet. App. 510, 513 (1992). 2. Entitlement to service connection for colon cancer is granted. Service connection may be established for a disability resulting from disease or injury incurred in or aggravated by service. 38 U.S.C. §§ 1110, 1131; 38 C.F.R. § 3.303. Evidence of continuity of symptomatology from the time of service until the present is required where the chronicity of a chronic condition manifested during service either has not been established or might reasonably be questioned. 38 C.F.R. § 3.303(b); see also Walker v. Shinseki, 708 F.3d 1331, 1340 (Fed. Cir. 2013) (holding that only conditions listed as chronic diseases in 38 C.F.R. § 3.309(a) may be considered for service connection under 38 C.F.R. § 3.303(b)). Regulations also provide that service connection may be granted for any disease diagnosed after discharge, when all the evidence, including that pertinent to service, establishes that the disability was incurred in service. 38 C.F.R. § 3.303(d). Generally, in order to prove service connection, there must be competent, credible evidence of (1) a current disability, (2) in-service incurrence or aggravation of an injury or disease, and (3) a nexus, or link, between the current disability and the in-service disease or injury. See, e.g., Davidson v. Shinseki, 581 F.3d 1313 (Fed. Cir. 2009); Pond v. West, 12 Vet. App. 341 (1999). Moreover, where a veteran served continuously for 90 days or more during active service, and cancer becomes manifest to a degree of 10 percent within one year from date of termination of such service, such disease shall be presumed to have been incurred in service, even though there is no evidence of such disease during the period of service. This presumption is rebuttable by affirmative evidence to the contrary. 38 U.S.C. §§ 1101, 1112, 1113, 1137; 38 C.F.R. §§ 3.307, 3.309. Veterans who, during active military, naval, or air service, served in the Republic of Vietnam from February 28, 1961 to May 7, 1975, shall be presumed to have been exposed to an herbicide agent, including Agent Orange, unless there is affirmative evidence to establish that the veteran was not exposed to any such agent during that service. 38 C.F.R. § 3.307 (a)(6)(iii). A veteran may be entitled to a presumption of service connection based on exposure to herbicides during the Vietnam Era if he is diagnosed with certain diseases. 38 U.S.C. § 1116; 38 C.F.R. §§ 3.307, 3.309. The appellant contends that the Veteran's colon cancer is related to service, to include as due to exposure to herbicides. The Board notes that VA has conceded the Veteran's exposure to herbicides. However, colon cancer is not a condition entitled to presumptive service connection based upon herbicide exposure under 38 C.F.R. § 3.309(e). Nevertheless, even if a claimant is not entitled to a regulatory presumption of service connection for a given disability, the claim must be reviewed to determine whether service connection can be established on a direct basis. See Combee v. Brown, 34 F.3d 1039, 1043-44 (Fed. Cir. 1994). The medical evidence of record reflects that the Veteran had been diagnosed with colon cancer. The record shows the Veteran was diagnosed with colon cancer in approximately May 2010. He received treatment for such until his death in February 2015. An August 2014 statement submitted by the Veteran indicated he was in the end stages of colon cancer and bedridden. The Veteran's death certificate reflects that the sole cause of his death was colon cancer. Thus, the first element of service connection, a current disability, is met. Accordingly, the remaining question in this case becomes whether such condition was related to service, to include exposure to herbicides therein. In April 2020, the appellant submitted a private medical opinion from Dr. S.D.P., who concluded it was at least as likely as not that the Veteran developed colon cancer as a result of his exposure to herbicide agents. She explained that colon/colorectal cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20 to 30 percent of patients with colorectal cancer have a family history. Most colon cancers are classified as adenocarcinoma, subdivided according to the grade of the tumor into low-grade and high-grade. Genetic factors, environmental exposures (including diet), and inflammatory conditions of the digestive tract are all involved in the development of colorectal cancer. Profound changes in the colonic mucosa lead to anomalies that eventually progress to cancer. Currently, it is known that colon cancer is caused by multiple genomic alterations which lead to genomic instability (GI). GI appears in molecular pathways of microsatellite instability (MSI) and chromosomal instability (CIN) with clinically observed case shares of about 15 to 20 percent and 80 to 85 percent. When chromosomal aberrations are generated at a markedly elevated rate, there occurs accelerated growth of premalignant adenoma. Also, epigenetic events such as abnormal DNA methylation can cause silencing of tumor suppressor genes or activation of oncogenes. These events compromise the genetic balance and ultimately lead to malignant transformation. Exposure to environmental toxicants causing human cancers, including colorectal cancer, has been extensively studied. A positive relationship between the exposure to several toxicants/chemicals and colorectal cancer development has been established through many laboratory and animal experiments, as well as through some epidemiologic studies and case-report studies. Credible estimates from the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposure is between 7 and 19 percent. Environmental toxicants have been implicated as one of the risk factors for sporadic colon cancer. This effect is increased when paired with consumption of Western diet (WD), which is another risk factor for colon cancer. Dr. S.D.P. cited to a 2005 study which explored the hypothesis that low-dose exposures to mixture of chemicals in the environment may be combining to contribute to environmental carcinogenesis. After noting the findings of the study, she stated that the analysis suggests that the cumulative effects of individual chemicals acting on different pathways, and a variety of related systems, organs, tissues, and cells could plausibly conspire to produce carcinogenic synergies. In addition, she stated that herbicide agents spread during Vietnam contained a number of chemicals which later were identified as carcinogens. Thus, it is plausible to consider that military (occupational) exposure to such substances is a risk factor for human cancers, including colorectal cancer. TCDD, appears to be a multisite carcinogen, a finding which is in agreement with the IARC, a branch of WHO, which has determined that TCDD is a category 1 "known human carcinogen" on the basis of the weight of scientific evidence from animal, human, epidemiologic, mechanistic, and mode-of-action studies. Also, the United States Environmental Protection Agency (EPA) has concluded that TCDD is "likely to be carcinogenic to humans" and the National Toxicology Program (NTP) regards TCDD as "known to be a human carcinogen." Dr. S.D.P. also described cacodylic acid. She stated that although in the medical literature there are numerous evidences that link herbicides to human cancers, the available analyses of an association between exposure to these chemicals of interest (COIs) and colorectal cancer risk are limited by the small number of cases and a lack of exposure specificity. Moreover, there have been very few studies of US Vietnam veterans that addressed colon cancers. Some of these studies are inadequate or have insufficient information to determine whether there is an association between exposure to COIs and these cancers. The fact is that the majority of these studies are based on statistical association and not on strict causality. Additionally, their conclusions are based on observed associations between exposure and health outcomes in human populations and do not address the likelihood that the health problems of any one individual are associated with or caused by the chemicals in question. Thus, the actual causative relationships (if exists) suffers a "dilution-like" statistical effect, which may be remote from a given true existent relationship which case-studies may reveal instead. In regard to the temporal relationship between exposure and disease, it is often difficult to define in studies of human populations. Many diseases do not appear immediately after exposure. Cancers, for example, might not appear for many years after exposure. The time between a defined exposure period and the occurrence of disease is often referred to as latent period. Exposures can be brief and (sometimes referred to as acute exposures) or protracted (sometimes referred to as chronic exposures). At one extreme, an exposure can be the result of a single event, as in an accidental poisoning. At the other extreme, a person exposed to a chemical that is stored in the body may continue to experience "internal exposure for years even if exposure from the environment has ceased. For example, the half-life of TCDD in exposed humans varies with body mass index (BMI), age, sex, and concentration in the body and has been found to vary from 0.4 to more than 10 years. She referenced a 2014 study of Korean veterans which reported that exposure to Agent Orange several decades earlier may increase the risk of cancers in all sites. She stated that TCDD is considered a non-genotoxic carcinogen because it does not produce changes in DNA sequences; however, because of the oxidative stress it produces, TCDD does have some genotoxic potential. The ability to induce oxidative stress contributes to TCDD's recognized activity as a potent tumor promoter. Moreover, a positive biological mechanism or other evidence of a causal relationship between COIscontained in Agent Orange and other herbicides used in Vietnamexposure and a health effect can be addressed since certain animal models and in vitro assays, including studies in human cells, have demonstrated direct association between some of these COIs (especially TCDD and cacodylic acid) and human cancers. Thus, the toxicologic evidence indicates that a connection of TCDD and perhaps cacodylic acid with cancer in humans is, in general, biologically plausible. It has been widely demonstrated that TCDD is an efficient ligand for the aryl hydrocarbon receptor (AHR), which has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD and benzoapyrene (BaP). The physician referenced a 2012 study which found that the activation of this receptor by TCDD, induces robust proliferation in two human colon-cancer cell lines through Src-mediated epidermal growth factor receptor activation. That finding suggests that TCDD and other AHR ligands may contribute to an increased proliferation of colonic cells. A 2016 study found that keratinocyte growth factor (KGF) AHR and CYP1A1 are overexpressed in colorectal cancer tissues. KGF promoted colon cancer cell growth through the AHR-cyclin D1 pathway in colon cancer cells. The physician stated that these studies support a plausible mechanism by the TCDD may influence colorectal cancers. Dr. S.D.P. explained that in the colon, repetitive selected smoldering inflammation increases the risk of developing cancer. An example of this extrinsic pathway is provided by ulcerative colitis and colorectal cancer. Obesity and other metabolic diseases as risk factors of cancer can be seen in this same perspective. For example, type 2 diabetes is associated with an increased risk of colorectal cancers as hyperinsulinemia, hyperglycemia, and inflammation are suggested to play a key role in the pathophysiology of cancer in diabetes. It is important to note that the Veteran was diagnosed with type 2 diabetes several years before his colon cancer diagnosis. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammations can result in immunosuppression, thereby providing a preferred background for tumor development. The mechanisms through which inflammation promotes intestinal neoplastic transformations are unclear, but an obvious mechanism could be related to the induction by inflammation of repeated cycles of epithelial wounding and repair, a condition that favors the occurrence of spontaneous mutations; furthermore, the inflammatory microenvironment could provide a clonal advantage to the mutated clones able to rapidly repopulate the healing mucosa. However, whatever the mechanism is through which inflammation promotes intestinal neoplasia, it was clearly supported by observational studies that colon cancer risk is clearly linked to the severity, duration, and extent of inflammation. The Veteran had a long-time bowel condition, diagnosed as irritable bowel syndrome (IBS), which is a chronic, relapsing, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, boating and changes in bowel habits that lack a known structural or anatomic explanation. Along with abdominal pain, recurrent diarrhea and urgency are the most frequently reported symptoms. The Veteran had a 30-plus years history of recurrent diarrhea, urgency, bloating and abdominal pain. Inflammation and immune activation are apparently involved in the pathogenesis or IBS as it has been reported in several scientific articles. All articles mention higher frequency of abdominal pain, bloating and diarrhea in IBS patients, the same symptoms the Veteran had for more than 30 years. All articles report that the chronic inflammatory process is the major pathophysiologic background of this conclusion. Dyspepsia is also mentioned a recurrent symptom in IBS patients. It is to note that the Veteran reported symptoms consistent with dyspepsia since he was in the Army and continued during the next 10 to 15 years with alternating remission and relapse periods. Also, the Veteran was diagnosed with diverticulosis in October 1989. According to some literature reports, diverticulosis is frequently seen in IBS patients as well. Interestingly, observational studies have been able to demonstrate that patients with a history of diverticular disease of the colon had an increased risk of colon cancer, especially in the left side, as colon cancer can arise from the mucosa in a colonic diverticulum. Currently, it is known that IBS increases the risk of developing colorectal adenocarcinoma, likely due to chronic inflammatory processes which over time lead to neoplastic transformation of the colonic enterocyte. It is known that TCDD has a role in promoting inflammation through diverse mechanisms among which its AHR-binding ability is paramount. Thus, exposure to TCDD may lead to AHR-mediated mechanisms promoting inflammation and immune-promoted inflammation in the gastrointestinal system. It is important to take into consideration that AHR functions include chemical and microbial defense, homeostasis of stem/progenitor cells and modulation of the immune system in barrier organs such as skin and the gut. Dr. S.D.P. summarized that the Veteran, who had IBS, which pathophysiology resides in chronic inflammation of the enteric mucosa and current medical literature points out that this condition increases the risk of colorectal cancer. The medical records show that some conditions, such as fructose intolerance, lactose intolerance, tropical sprue thought to be associated with IBS, were ruled out in 1989. The Veteran had a diagnosis of diverticulosis. Diverticulosis and its complications are considered inflammation-based colon pathologies. Colorectal cancer has been reported to originate from left colon diverticula. A large body of scientific articles from the last 20 years (at least) has shown solid evidence that relates chronic inflammatory processes and neoplastic transformation in any human tissue or organ. The process of tissue/cellular inflammation-promoted-malignant-transformation progresses silently over many years until overt symptoms and signs of cancer become evident. Thus, cancer manifestation usually occurs after many years of sustained inflammation. Dr. S.D.P. stated that the Veteran was exposed to herbicides, including but not limited to Agent Orange, which components (COIs) are known carcinogens, such as TCDD. They exert their carcinogenic effects through various mechanistic pathways including but not limited to oxidative stress and activation of AHR-mediated pathways. Interestingly, the majority of the above pointed out mechanistic pathways for the inflammation-promoting action of COIs contained in Agent Orange and other herbicides, are involved as well in human cancer development. The Veteran suffered from other conditions for which TCDD has been recognized as a causative factor: type 2 diabetes mellitus, hypertension, dyslipidemia, and hypothyroidism, as TCDD triggers diverse inflammatory processes mostly based on tissue oxidative stress mechanisms and AHR medicated inflammation. The Veteran also suffered from two historically different types of non-melanoma skin cancer. Non-melanoma skin cancers have been related to TCDD present in Agent Orange. The physician cited to a study, noting that TCDD has been shown to produce non-melanoma skin cancers in animal models. The physician noted that the Veteran's medical history is negative for other colorectal cancer risks such as excessive tobacco and alcohol use in the last 40 years previous to the colon cancer diagnosis. She further stated that his medical history does not show any post-service toxicant/chemical exposure from separation until his colon cancer diagnosis. Therefore, based on the Veteran's medical history, extensive revision of current scientific literature and on the above discussion, it is at least as likely as not that the Veteran developed left colon cancer, diagnosed in May 2010 as colorectal adenocarcinoma, as a result of his exposure to COIs present in herbicides, including but not limited to TCDD contained in Agent Orange. Over time, the Veteran's exposure to COIs present in herbicides, including but not limited to Agent orange more likely than not caused: 1) direct carcinogenic effect upon his colonic mucosa leading to malignant transformation as it has been discussed above, and 2) a state of chronic inflammation of his colonic mucosa (manifested as IBS shortly after service separation) that favored neoplastic cellula transformation in the left colon's mucosa. Over time, both mechanisms, acting synergically, led to progressive colonic adenomatous cellular changes. In turn, these changes manifested as colon adenocarcinomadiagnosed in May 2010, which led to the Veteran's death in February 2015. She further stated that it was also her opinion that the fact that the Veteran suffered from at least two conditions concurrently accepted as being caused by TCDD exposure, represents strong evidence for the damage caused by the Veteran's exposure to TCDD. This fact should be considered as an important element supporting the likelihood of a causative relationship between Agent Orange/TCDD and colon cancer as well. Nevertheless, it is very important to stress out that these diseases (type 2 diabetes mellitus and hypertension) are totally different and independent from colon cancer; however, what they have in common is that they share the same basic pathophysiological starting event, the very basic biochemical mechanisms initiate a cascade of events which leads to their development; that is: they have a common starting point or trigger. This common trigger is the exposure to TCDD which binds to AHR and/or causes oxidative stress which in turn, provokes immunological/inflammatory/molecular derangements capable to induce tissue(s) malignant transformation as discussed above. Upon review of the record, the Board finds the private opinion linking the Veteran's colon cancer to service, to include exposure to herbicide agents therein to be competent and probative. Accordingly, affording the appellant the benefit of the doubt, service connection for colon cancer is warranted for accrued benefits purposes. 3. Entitlement to service connection for the cause of the Veteran's death is granted. In order to establish service connection for the cause of the Veteran's death, the evidence must show that a disability incurred in or aggravated by active service was the principal or contributory cause of death. 38 C.F.R. § 3.312. Service connection for the cause of a Veteran's death may be demonstrated by showing that the Veteran's death was caused by a disability for which service connection had been established at the time of death or for which service connection should have been established. The Veteran died in February 2015, and the death certificate lists the immediate cause of death as colon cancer. The Board notes that, at the time of the Veteran's death, service connection was not in effect for colon cancer. However, as noted above, the Board has found the Veteran's colon cancer to be related to his exposure to herbicide agents during his active service. Accordingly, the Board concludes that the Veteran's underlying colon cancer, the immediate cause of the Veteran's death is due to the Veteran's active service as well, and, therefore, service connection for the Veteran's cause of death is granted. 38 U.S.C. §§ 1110, 1116; 38 C.F.R. §§ 3.303, 3.307, 3.309(e), 3.312. B. G. LeMoine Acting Veterans Law Judge Board of Veterans' Appeals Attorney for the Board S. Medina, Associate Counsel The Board's decision in this case is binding only with respect to the instant matter decided. This decision is not precedential and does not establish VA policies or interpretations of general applicability. 38 C.F.R. § 20.1303.