INSIDE GENETIC PREDISPOSITION

PART 1: MUTAGEN HEREDITY AND ENVIRONMENTAL CANCER EXPOSURES

By: Lennard M. Gettz, Ed.D  /  Edited by: Roberta Kline, MD

First responders of every branch (police, firefighters, paramedics), as well as construction cleanup contractors, were exposed to the many toxic hazards around the World Trade Center (WTC) as a result of the events on 9/11/2001.  For the more than 91,000 individuals involved in this massive response and cleanup effort [1], exposure to the toxicants from dust, smoke, and incendiary chemicals has led to concerns for cancer, diseases, and other health injuries post-exposure.  The James Zadroga 9/11 Health and Compensation Act enacted the World Trade Center Health Program, a federal commitment to offer comprehensive care for 9/11-related conditions. [2]

Numerous environmental contaminants have been shown to have potential carcinogenic (cancer-causing) consequences. [3] Events such as 9/11 are just some of the scenarios that have alerted government agencies, the medical community, and individuals to study the types of common cancers from each scenario.  These exposures also bring new (and heightened) concerns for gene mutations that may be inherited or passed down to the next generations of those directly impacted.

"Learning about how cancer and other illnesses work... I would hate to contract this on the job and give this to my kids", states FDNY Ret. FF Sal Banchitta- 9/11 responder. "Firefighters get a lot of training and gear to protect us from exposure- but let's face it... part of the risk of the job is that there IS no 100% guarantee- ever!  Looking back on all this, from the local house fires of burning plastics and PVC's to the many chemicals and airborne poisons in ground zero-- exposure came from anywhere.  You can only hope that you're not someone who's predisposed, but you never know." 

According to the NCI (National Cancer Institute), up to 10% of all cancers may be caused by inherited genetic changes. Cancer itself (or genetic changes in tumor cells) cannot be inherited by children of cancer patients but a genetic change or mutation that increases the risk of cancer can be passed down (inherited) if it is present in a parent's egg or sperm cells. It is for this reason why cancer may sometimes appear to run in families.  [4]

WTC-RELATED CANCERS

There are now more than 15 cancers specifically associated with exposure to the WTC toxins, with prostate and breast cancer being among the top 3. [5]. Not only do survivors have higher rates of these cancers, but they are often more aggressive. Recent research has demonstrated that DNA mutations and epigenetic changes due to toxin exposures may play a role. [6, 7, 8] 

PART 2: TODAY'S GENETICS

In an exclusive interview about the science of gene expression, genomic specialist Dr. Roberta Kline, professor at the University of Western States, offered clarity on the fundamentals of the human blueprint: what DNA is, what it does, the impact of alterations to DNA on health, and how this is influenced by environmental exposures. 

Genes are specific regions of DNA that contain the code for all of the proteins that run our biology. Gene expression is the ultimate result of this complex process, and gene expression research has greatly accelerated the study of human biology and improved the practice of medicine. Up until the completion of the Human Genome Project in 2003, much of the focus had been on studying rare mutations linked to specific inherited diseases and cancers. We now know that these alterations of the DNA code are not the only ways people can be predisposed. 

The most common types of changes in DNA are called SNPs (single nucleotide polymorphisms), and we each have millions of these. These SNPs can alter our biochemistry and biology, but they typically have a much smaller effect individually than mutations. However, the additive effect of multiple SNPs can create significant predispositions to (or protection from) most diseases, including cancer. 

The latest gene expression research has added a third layer called epigenetics. Epigenetic changes don’t affect the DNA or genetic code itself. Rather, they respond to environmental cues to control when genes are turned on or off. Therefore, epigenetic changes can be easily modified throughout a person’s lifetime.

These processes all work together, and all of them can be inherited. Depending on diet, lifestyle, exercise, stress, medications, and environmental exposures, their impact can be increased or decreased. For example, someone with mutations, SNPs, or epigenetic changes that impair their ability to detoxify environmental chemicals can have a higher risk of DNA damage that can lead to disease or cancer. Diet and lifestyle strategies can counteract some of this risk - or can make it worse. This can help explain why not everyone exposed to the same toxins is affected in the same way, and why the same dietary and lifestyle factors can affect people’s health differently.

GENETIC PREDISPOSITION TESTING

With the existence of cancers in the family, physicians may recommend genetic testing.  Inherited mutations account for approximately 10% of all cancers, and these tend to be more aggressive and occur at an earlier age. [8] Genetic mutations have been identified for certain forms of pancreatic cancer, colorectal cancer, prostate cancer, or breast or ovarian cancer.  These tests for cancers such as Breast, Ovarian, and Pancreatic are known to target pathogenic/ly pathogenic (P/LP) variants associated with increased risk (including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. [10, 11]

Genetic testing supports proactive prevention initiatives and active surveillance for these specific cancers that continue to prevail. Gene SNP testing can further support personalized prevention and screening strategies. While epigenetics is emerging as another tool in efforts to identify predispositions and personalize strategies, it is still more informative than prognostic at this time.

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PART 3: "BOTH MY PARENTS HAD CANCER... I NEED TO TEST!

Samantha Hunt, 24 is a young cancer awareness advocate due mostly to the upbringing of two cancer survivors who are outspoken about environmental cancers and proactive testing ("Get Checked NOW!" program).  She is in a graduate program for social work and grew up in a household in support of prevention and early detection.

Since she was 9 years old, Samantha took on personal studies on breast cancer when she watched her mother (Jennifer) undergo a bilateral mastectomy for early-stage breast cancer.  Samantha's father was diagnosed with early-stage prostate cancer, and her maternal aunt also had breast cancer. By her late teens into her college years, Samantha was convinced that she needed to have early screening, which is when she discovered she had dense breast tissue- a condition that is present in over half of women in the U.S.  [12]

Though currently testing negative for cancer, Samantha continues to undergo early detection through gene testing, ultrasound screening and maintains a significantly strict lifestyle of prevention (eating healthy/organic foods, no sugar, exercise, organic foods etc).  Early in life, she learned the value of staying proactive and getting a second opinion- never resting on reassuring words from physicians.  "Early on, my gyno didn't express any real sense of urgency about me getting an ultrasound test but gave me the referral just to make me happy...", stated Ms. Hunt.  "Even today (and sometimes even in the past with other breast exams), I often feel like they do it so quickly and carelessly, and I feel stressed out after...  I'm not convinced that I'm getting a proper examination!"

Samantha has received a total of 4 biopsies due to the "abnormally dense" breast tissue- a concern that scientists are now linking to breast cancer. [13] At an early age, Samantha took on a significant leadership role in her health to approve the biopsies despite the risk and concerns from her parents. "After my first sono, they found me to be 'very lumpy' and called on me to get a biopsy.  None of us were excited about this but if I was going to get any peace of mind, I made a decision to go for it and I'm glad I did. Honestly think I'd be more anxious knowing there's something that a doctor recommended that I should get a biopsy on!"

References:

1) https://www.nyc.gov/site/911health/enrollees/rescue-recovery-workers.page

2) The Toll of Heroism: Increased Cancer Incidence Among 9/11 Responders 

September 9, 2022 by Calley Jones, PhD  https://www.aacr.org/blog/2022/09/09/the-toll-of-heroism-increased-cancer-incidence-among-9-11-responders/

3) Tuminello S, Nguyen E, Durmus N, et al. World Trade Center Exposure, DNA Methylation Changes, and Cancer: A Review of Current Evidence. Epigenomes. 2023; 7(4):31. https://doi.org/10.3390/epigenomes7040031

4) https://www.cancer.gov/about-cancer/causes-prevention/genetics

5) https://www.cdc.gov/wtc/ataglance.html#top15Cancers 

6) Yu, H., Tuminello, S., Alpert, et al/ (2022) Global DNA methylation of WTC prostate cancer tissues show signature differences compared to non-exposed cases. Carcinogenesis, 43(6), 528-537. https://doi.org/10.1093/carcin/bgac025

7) Tuminello S, Zhang Y, Yang L, et al. Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer. Int J Environ Res Public Health. 2022 Apr 22;19(9):5104. doi: 10.3390/ijerph19095104. 

8) Jasra, S., Giricz, O., Pradhan, K., et al (2022). High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster. Nature Medicine, 28(3), 468-471. https://doi.org/10.1038/s41591-022-01708-3

9) https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet

10) Daly MB, Pal T, Maxwell KN, et al. NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024. Journal of the National Comprehensive Cancer Network 2023; 21(10):1000–1010. doi: 10.6004/jnccn.2023.0051. 

11) Garber J, Offit K. Hereditary cancer predisposition syndromes. Journal of Clinical Oncology 2005; 23(2):276–292. 

12) https://www.cdc.gov/cancer/breast/basic_info/dense-breasts.htm

13) Lester, S. P., Kaur, A. S., & Vegunta, S. (2022). Association Between Lifestyle Changes, Mammographic Breast Density, and Breast Cancer. The Oncologist, 27(7), 548-554. https://doi.org/10.1093/oncolo/oyac084